Kiyoaki Tsukahara

Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma.

BACKGROUND The treatment of bone metastasis in association with thyroid cancer represents a difficult challenge. Given the paucity of patients with bone metastasis and the difficulty of treating this disease, few studies have investigated the clinical features and prognostic factors of bone metastasis from differentiated thyroid cancer. METHODS During the 31-year-period from 1976 to 2006, a total of 1,398 patients underwent initial thyroidectomy at Cancer Institute Hospital for differentiated thyroid carcinomas, including standard papillary thyroid carcinoma, papillary microcarcinoma (primary tumor diameter < or =1.0 cm), and follicular thyroid carcinoma. Among these, 25 (2%) patients displayed bone metastasis at initial presentation (synchronous) and 27 patients showed bone metastasis during follow-up (metachronous). The records for these 52 patients were reviewed retrospectively to identify prognostic factors and analyze treatment strategies. RESULTS Univariate analysis for disease-specific survival indicated metachronous bone metastasis and the presence of distant metastasis at sites other than bone as indicators of significantly worse prognosis. The type of cancer (papillary thyroid carcinoma versus follicular thyroid carcinoma) was not a significant indicator of prognosis; however, patients with papillary microcarcinoma showed significantly worse survival than patients with standard papillary and follicular thyroid carcinoma. A significant survival advantage was observed among patients who underwent radioactive iodine therapy, and better prognosis seemed to be obtained with greater doses of radioactive iodine. Operative resection of metastatic bone lesions also seemed to be associated with better prognosis. A multivariate analysis for disease-specific survival identified the coexistence of distant metastasis at sites other than bone as the only independent variable indicative of poor prognosis. CONCLUSION In the absence of definitive, effective treatments for this disease, radioactive iodine therapy combined with resection of bone metastasis, wherever possible, seems to represent the most potent therapy available. Although bone metastasis is a strong sign of poor prognosis, early detection and administration of appropriate therapy using radioactive iodine seems likely to improve the survival rate and quality of life in patients with bone metastasis from differentiated thyroid carcinoma.

Surgical management of tracheal shaving for papillary thyroid carcinoma with tracheal invasion

Conclusion: Patients showed improved quality of life following tracheal shaving and the carcinoma was well controlled locally, as long as invasion had not progressed to the mucosal surface of the trachea. However, compared with papillary thyroid carcinoma (PTC) with no tracheal invasion, metastasis was common and invasion of organs other than the trachea was frequent, putting many patients into the high-risk group. The clinical course for such patients thus requires careful monitoring, with particular attention to metastasis to other locations. Tracheal shaving can be recommended for patients with PTC with tracheal invasion. Objectives: Macroscopically, in cases where invasion into the trachea has not reached the tracheal mucosa surface, we perform tracheal surface resection (tracheal shaving). We retrospectively investigated rates of local control, metastasis and survival in patients who had undergone tracheal shaving. Patients and methods: Subjects comprised 22 patients with PTC who underwent tracheal shaving between January 1994 and December 2005. Results: Local control was achieved in 21 patients (95%), and metastasis was seen in 6 patients (27%). With two patients dying from causes other than cancer, 5- and 10-year survival rates were 93% and 41%, respectively. The two surviving patients are still cancer-bearing.

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.

Randomized Phase III Trial of Adjuvant Chemotherapy with S-1 after Curative Treatment in Patients with Squamous-Cell Carcinoma of the Head and Neck (ACTS-HNC)

Background We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients were randomly assigned to the UFT group (300 or 400 mg day-1 for 1 year) or the S-1 group (80, 100, or 120 mg day-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety. Results A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group. Conclusions Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN. Trial Registration ClinicalTrials.gov NCT00336947 http://clinicaltrials.gov/show/NCT00336947

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.

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.

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.

Regulatory T-cell infiltration in tongue squamous cell carcinoma

Abstract Conclusion: In tongue squamous cell carcinoma (SCC), high levels of regulatory T-cell (Treg) infiltration in tumor nests are observed in the cases with poor prognosis. Objectives: The role of Tregs in head and neck cancers remains unclear. The aim of this study was to observe the distribution of Tregs in different stages of tongue SCC and estimate the effects on prognosis. Methods: Thirty-four cases with tongue SCC were examined immunohistochemically for CD4, CD8, and Forkhead box P3 (Foxp3). Immunoreactive cells were counted in cancer stroma and nest regions, and relationships between cell numbers and disease-free survival rates were analyzed. Results: In the 34 cases, univariate analysis for disease-free survival indicated high-level infiltration of Tregs (CD4+Foxp3+) into both cancer nests and stroma and presence of helper T (CD4+Foxp3–) cells in cancer stroma as potential predictors of significantly worse prognosis. In early-stage cases (stage I/II), high-level infiltration of Tregs in cancer nests correlated significantly with poor disease-free survival rate. Multivariate analysis for disease-free survival found no independent variables.

A case of high-pitched diplophonia that resolved after a direct pull of the lateral cricoarytenoid muscle.

Various approaches have been employed for the surgical treatment of unilateral vocal cord paralysis. Recently, we performed a direct pull of the lateral cricoarytenoid muscle in a case of high-pitched diplophonia with little difference between the right and left vocal cord levels and obtained favorable results. The patient was a 66-year-old male who consulted our hospital with chief complaints of husky voice and abnormal sensation in the pharyngolaryngeal region. Cerebellum/brainstem inflammation was diagnosed in February 2002 and appropriate treatment was instituted. Despite an improvement in the patients systemic condition, right vocal cord paralysis remained. Although there were no abnormalities in the vocal range for ordinary speech, diplophonia was noted at high pitches, and synchronization could not be observed using stroboscopy. Therefore, the patient was operated on in October 2002. The high-pitched diplophonia disappeared and stroboscopy revealed favorable mucosal waves at high pitches. Thus, direct pulling of the lateral cricoarytenoid muscle appears to be a useful procedure, even in a case of mild unilateral vocal cord paralysis.

Biomarker immunoprofile in salivary duct carcinomas: clinicopathological and prognostic implications with evaluation of the revised classification

Salivary duct carcinoma (SDC) is an uncommon, aggressive malignant neoplasm histologically resembling high-grade mammary ductal carcinoma. SDC can arise de novo or ex pleomorphic adenoma. To clarify the correlation of biomarker immunoprofile with clinicopathological findings and clinical outcome of SDC, we conducted immunohistochemistry for EGFR, HER2, HER3, AR, CK5/6, p53, and Ki-67, along with HER2 fluorescence in situ hybridization in 151 SDCs. SDCs ex pleomorphic adenoma more commonly overexpressed EGFR, HER2, HER3, and Ki-67 than de novo SDCs (P = 0.015, < 0.001, 0.045, and 0.02, respectively). In multivariate analysis, AR− and CK5/6+ were associated with shorter progression-free survival (P = 0.027 and 0.004, respectively). Moreover, patients with p53-extreme negative/positive demonstrated poorer overall survival (P = 0.007). On assessing the revised classification by the combination of biomarker expression, the percentages of each subtype were as follows: ‘apocrine A’ (AR+/HER2−/Ki-67-low) (24%), ‘apocrine B’ (AR+/HER2−/Ki-67-high) (18%), ‘apocrine HER2’ (AR+/HER2+) (35%), ‘HER2-enriched’ (AR−/HER2+) (12%), and ‘double negative’ (AR−/HER2−) (11%). ‘Double negative’ was further subclassified into ‘basal-like’ (EGFR and/or CK5/6+) (7%) and ‘unclassified’ (3%). Consequently, patients with ‘apocrine A’ showed a better progression-free survival than those with any other subtypes. Our revised immunoprofiling classification was valuable for predicting the survival and might be useful in personalized therapy for patients with SDC.