Ryoji Tokashiki

Dedifferentiated Adenoid Cystic Carcinoma: A Clinicopathologic Study of 6 Cases

Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade “dedifferentiated” carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34–70 y). The mean size of the tumors was 3.5 cm (range, 1.7–6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6–69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67–labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.

Usefulness of three-dimensional computed tomography of the larynx for evaluation of unilateral vocal fold paralysis before and after treatment: technique and clinical applications

Laryngoplasty is well-known technique for unilateral vocal fold paralysis (UVFP). However, operation result are sometimes not as good as expected before surgery. Three-dimensional Computed tomography (3DCT) is useful for visualizing complicated intralaryngeal structures. Moreover, 3DCT is suited for analyzing the movement of the vocal fold and arytenoid cartilage because the technique is based on actual data from live patients. We have been used 3DCT of the Larynx for evaluation of UVFP before and after treatment. We uncovered some new findings about UVFP and reasons of unsatisfactory outcomes after operation. Technique and clinical applications of 3DCT for UVFP are outlined in this paper.

Globus sensation caused by gastro epophageal reflux disease

OBJECTIVES This study was designed to examine whether or not gastro esophageal reflux disease (GERD) is implicated in globus sensation. METHODS The subjects were 25 patients (16 men/9 women; mean age: 51, range 25-69 years) complaining of globus sensation with one or more of four laryngeal findings suspected of having GERD, such as pooling of saliva, erythema of posterior one-third of larynx, inter-arytenoids edema, and granuloma. All 25 patients were administrated a proton pump inhibitor (PPI) for a period of 8 weeks. All were given esophageal endoscopies, laryngoscopes, and questionnaire before and after PPI dosing. The questionnaire survey was conducted to investigate changes in globus sensation and three symptoms specific to GERD including heartburn, regurgitation, and belching. Subjective symptoms were totalled by the over all scores of the three subjective symptoms which served as an index of severity of GERD. RESULTS Fifty-two percent (13/25) of patients had reflux esophagitis. The esophagitis were improved after PPI administration except one case. The incidences of GERD symptoms were high (heart burn 68% (17/25), belching 49% (10/25) and regurgitation 76% (19/25)), and most of these symptoms ameliorated by PPI administration. The laryngeal findings were improved in all patients. Subjective symptoms were improved in 68% (17/25) of globus patients. The improvement rate of total score (before PPI dosing/after PPI dosing) was compared between the two groups: one with improved globus sensation (17 patients) and the other without (8 patients). The improvement rate was significantly higher in the group with improved globus sensation (P<0.05). This means that globus sensation improved because of the improvement in GERD. CONCLUSION GERD is therefore concluded to be an inducing factor of globus sensation.

Characterization of arytenoid vertical displacement in unilateral vocal fold paralysis by three-dimensional computed tomography

The paralyzed arytenoid is not immobile and is subjected to passive movement during phonation. If anatomical changes during inspiration and phonation are compared by three-dimensional computed tomography (3D CT), it is possible to observe vertical movement of the paralyzed arytenoid. Our aim was to use 3D CT to examine the characteristics of 3D arytenoid movement in unilateral vocal fold paralysis (UVFP). This is a prospective study. A total of 61 patients (18 females and 43 males) with UVFP who had undergone 3D CT imaging between April 2005 and January 2007 were included. Cricoid and arytenoid cartilage was imaged by 3D CT. We detected the movements of the paralyzed side when comparing inspiration and phonation. The degree of cranial displacement of the paralyzed arytenoids was classified into three grades (I for mild to III for severe). The mean flow rate (MFR) was calculated for each grade. By comparing the MFR of each grade with the normal control group, we determined whether cases would worsen according to grade. Passive gliding movement of the paralyzed arytenoids was found in 90.7% of cases. In all cases, the paralyzed arytenoids were displaced cranially compared to the unaffected side. MFR worsened significantly as the grade became more severe. We believe that the passive gliding movements observed when comparing inspiration and phonation are characteristic of paralysis. Even in mild cases, the paralyzed arytenoids are passively displaced cranially during phonation, and the degree of this displacement is one indicator that can be used to evaluate the severity of UVFP.

New approach to diagnose arytenoid dislocation and subluxation using three-dimensional computed tomography

Understanding the complex three-dimensional (3D) arrangement of the arytenoid cartilage is necessary for diagnosing arytenoid dislocation (AD) and arytenoid subluxation (AS). We examined the 3D arrangements of AD and AS (AD/AS) cases by region and considered their new diagnoses. This retrospective study included 2 patients with AD, 10 with AS, and 23 with unilateral vocal fold paralysis (UVFP) for comparison. The etiologies were intubation-induced and idiopathic. We classified the AD/AS position into four joint regions: mediocaudal, laterocaudal, mediocranial, and laterocranial. We generated 3D computed tomography (3DCT) images during rest and phonation to analyze functional movements. We attempted to compare the endoscopic findings and 3DCT images of patients with UVFP and AD/AS. To examine the joint status, we especially focused on the position and movements of the muscular process (MP) on the joint because the arytenoid facet is mainly located on the back of the MP. We were able to obtain endoscopic and 3DCT findings characteristic of each AD/AS region. The dislocated MPs were localized to the mediocaudal, mediocranial, and laterocranial regions. Two AD cases were diagnosed due to complete separation of the joint surfaces during rest and phonation. The finding of MPs displacing partially outside the cricoid facet is common to both severe UVFP and AS. The most important differentiation point was that the MP in UVFP cases was located on both the medial and lateral side regions of the joint, but that of AS was on one side region only. Furthermore, no cases of passive gliding movements characteristic of UVFP that have been described previously by us were observed in AD/AS cases. AD can be diagnosed by findings of complete joint separation. AS can be diagnosed based on positions and movements distinct from those of UVFP.

Therapeutic effects of a new photosensitizer for photodynamic therapy of early head and neck cancer in relation to tissue concentration.

OBJECTIVE Talaporfin sodium (Laserphyrin, Meiji Seika, Tokyo, Japan) is a second-generation photosensitizer developed in Japan. It is characterized by both mild and short-term skin photosensitivity. The objective of this study was to evaluate the efficacy and the pharmacokinetic characteristics in tumor tissues in patients with head and neck cancer. METHODS (1) Four hours after administration intravenous injection of talaporfin sodium (40 mg/m(2)), 100mg tissue specimens were taken from the central part of the tumor. The samples were analyzed by reverse phase liquid chromatography and concentrations were measured. (2) Four hours after intravenous injection of talaporfin sodium (40 mg/m(2)), we gave 60-150 J/cm(2) of 664 nm laser irradiation with a diode laser (PD laser, Panasonic, Japan). Biopsies were performed at 4 weeks and at 3 months after treatment and periodically thereafter to confirm the treatment efficacy of photodynamic therapy (PDT). RESULTS Of the 14 patients who grope informed consent, more than 1 microg/g of talaporfin sodium was found in the tumor tissues in 13. Moreover, in 9 patients, tumor-to-normal-tissue ratios ranged from 2.32:1 to 5.69:1, which indicates that more than double the amount of talaporfin sodium was maintained within the tumor than in normal tissues. We have enrolled 22 patients with head and neck cancer with no clinically recognizable metastases after obtaining written informed consent to participate in this study. PDT using talaporfin sodium exhibited the equivalent efficacy to that of conventional PDT using hematoporphyrin derivative (HpD). CONCLUSIONS The results using a combination of talaporfin sodium and PD laser achieved a primary treatment outcome equivalent to that of conventional PDT. This method has also proven to be advantageous because of the reduced incidence of side effects such as photosensitivity and local edema.

Three-dimensional laryngeal model for planning of laryngeal framework surgery

Conclusion. The three-dimensional prototype model was useful for planning of laryngeal framework surgery. Objective: To discuss the usefulness of a three-dimensional laryngeal model for laryngeal framework surgery. Materials and methods. A three-dimensional laryngeal model was created based on the postoperative helical computed tomography (CT) data of the larynx (case 1) which underwent lateral cricoarytenoid muscle (LCA) pull surgery. LCA pull surgery is a kind of arytenoid adduction for unilateral vocal cord paralysis. A three-dimensional model of case 1 larynx was prototyped using a selective laser sintering method. In case 1, the patients voice did not improve after LCA pull surgery. The three-dimensional model revealed that the original surgical procedure was not appropriate to obtain optimal arytenoid adduction. According to the analysis of this three-dimensional model, we changed the surgical approach and performed this new refined LCA pull surgery on another patient with unilateral vocal cord paralysis (case 2). Results. We were able to pull LCA precisely in case 2. Three-dimensional CT of case 2 after refined LCA pull surgery allowed the correct pulling of LCA and complete adduction of arytenoid. The postoperative voice improved remarkably.

A new procedure of arytenoid adduction combined with type I thyroplasty under general anesthesia using a laryngeal mask

Laryngeal framework surgery is usually performed under local anesthesia. However, some patients are unable to tolerate extended surgery. A case of an 82-year-old woman who underwent medialization thyroplasty and arytenoid adduction of direct lateral cricoarytenoid (LCA) muscle pulling at the same time under general anesthesia using a laryngeal mask is reported. Endoscopic observation through the laryngeal mask allows direct visual control of the vocal cord. The LCA pulling method does not touch the posterior border of the thyroid cartilage so that the laryngeal mask does not disturb the arytenoid adducts.

Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux

AIM To investigate the effect of rikkunshito on laryngopharyngeal reflux (LPR) symptoms and gastric emptying in patients with proton-pump inhibitor (PPI)-refractory LPR. METHODS In total, 22 patients with LPR were enrolled. Following a 2-wk treatment with PPI monotherapy, PPI-refractory LPR patients were randomly divided into two treatment groups (rikkunshito alone or rikkunshito plus the PPI, lansoprazole). LPR symptoms were assessed using a visual analog scale (VAS) score, gastrointestinal symptoms were assessed using the gastrointestinal symptom rating scale (GSRS), and gastric emptying was assessed using the radio-opaque marker method prior to and 4 wk following treatments. RESULTS The 4-wk treatment with rikkunshito alone and with rikkunshito plus the PPI significantly decreased the globus sensation VAS scores. The VAS score for sore throat was significantly decreased following treatment with rikkunshito plus PPI but not by rikkunshito alone. Neither treatment significantly changed the GSRS scores. Rikkunshito improved delayed gastric emptying. We found a significant positive correlation between improvements in globus sensation and in gastric emptying (r² = 0.4582, P < 0.05). CONCLUSION Rikkunshito improved globus sensation in patients with PPI-refractory LPR, in part, because of stimulation of gastric emptying. Thus, rikkunshito is an effective treatment for PPI-refractory LPR.

Direct pull of lateral cricoarytenoid muscle for unilateral vocal cord paralysis

Conclusion. Lateral cricoarytenoid muscle-pull surgery (LCA pull) is a safe and effective method for the treatment of unilateral vocal cord paralysis. Objective. To evaluate the results of an improved method of LCA pull for unilateral vocal cord paralysis. Material and methods. Thirteen patients with unilateral vocal cord paralysis underwent LCA pull between April 2003 and January 2004. A small window was made in the posterior lower part of the thyroid cartilage and 2–3 mm in a cranial direction to the lower edge of the thyroid cartilage. The inner perichondrium was carefully removed to expose the LCA muscle. A 4-0 nylon suture placed through the LCA muscle was pulled to adduct the arytenoid and was tied to the anterior lower part of the thyroid cartilage. All cases were treated by LCA pull alone. In all cases, the maximum phonation time was measured and an auditory evaluation was performed using the grade, roughness, breathiness, asthenia and strain scale. The airflow rate was measured in five cases. Results. Vocal improvement was obtained in 11/13 cases (85%). One of the unimproved cases had cricoarytenoid joint ankylosis. No complications were observed.