SOX10 is a novel marker of acinus and intercalated duct differentiation in salivary gland tumors: a clue to the histogenesis for tumor diagnosis.

Salivary gland tumors are relatively rare and morphologically diverse and heterogeneous tumors; therefore, histogenesis-based tumor markers are sorely needed to aid in diagnosing and determining the cell type of origin. SRY-related HMG-box 10 (SOX10) protein is a transcription factor known to be crucial in the specification of the neural crest and maintenance of Schwann cells and melanocytes. In addition, positive expression has also been implicated in the major salivary gland. Here, we examined SOX10 expression in various salivary gland tumors to correlate this expression with myoepithelial markers. Overall, 76 malignant and 14 benign tumors were examined. SOX10 expression clearly delineated two distinct subtypes of human salivary gland tumors; acinic cell carcinomas, adenoid cystic carcinomas, epithelial-myoepithelial carcinomas, myoepithelial carcinomas, and pleomorphic adenomas, including the pleomorphic adenoma component of carcinoma, were SOX10 positive, while salivary duct carcinomas, mucoepidermoid carcinomas, an oncocytic carcinoma, Oncocytomas, and Warthin tumors were SOX10 negative. Also, SOX10 was expressed in solid-type or non-specific morphology salivary gland tumors, but was not expressed in poorly differentiated squamous cell carcinomas. In normal human salivary gland tissue, SOX10 expression was specific to the nuclei of acini and both luminal and abluminal cells of intercalated ducts but not in other sites. Moreover, the murine model suggested that SOX10 continued to be expressed from the developmental stage to adulthood in the acinar and both luminal and abluminal intercalated ducts in the major salivary gland. Thus, SOX10 is a novel marker for diagnosing and understanding the histogenesis of salivary gland tumors.

Thoracoacromial vessels as recipients for head and neck reconstruction and cause of vascular complications.

BACKGROUND: The choice of recipient vessels is an important factor for successful head and neck reconstruction. Finding good recipient vessels for neck microsurgery can be difficult after patients have undergone radiation therapy, previous neck dissection or developed neck infections due to pharyngocutaneous fistulae. Thoracoacromial arteries and veins can be good alternatives to common recipient vessels in such patients. We reviewed the complications, advantages and disadvantages associated with using thoracoacromial arteries and veins as recipient vessels. METHODS: We reviewed eight patients whose thoracoacromial arteries and veins served as recipient vessels for head and neck reconstruction between 2002 and 2009. Preoperative status, reconstruction method and operative outcomes with complications were evaluated. RESULTS: Postoperative complications related to microsurgical anastomosis developed in two of the eight patients. One arterial and venous thrombosis developed in each patient. We considered that the arterial thrombosis was derived from a technical problem with the operation and the venous thrombosis was derived from postoperative external pressure. CONCLUSIONS: Thoracoacromial arteries and veins are good recipient vessels for patients who have undergone ablative or reconstructive surgery, radiation therapy, or have a neck infection due to complications. However, we believe that using these vessels as recipients requires specific precautions that differ from those associated with general head and neck reconstruction.

Multicenter phase II study of an opioid-based pain control program for head and neck cancer patients receiving chemoradiotherapy.

BACKGROUND: The aim of this multi-center phase II study was to clarify the clinical benefit of an opioid-based pain control program for head and neck cancer patients during chemoradiotherapy. PATIENTS AND METHODS: Head and neck cancer patients who were to receive definitive or postoperative chemoradiotherapy were enrolled. The opioid-based pain control program consisted of a three-step ladder, with basic regimens of: The primary endpoint of this study was compliance with radiotherapy. RESULTS: A total of 101 patients from 10 institutions were registered between February 2008 and May 2009 and included in the analysis. The major combination chemotherapy regimen was cisplatin alone (76%). The rate of completion of radiotherapy was 99% and the rate of unplanned breaks in radiotherapy was 13% (13/101, 90% confidence interval: 9.9-16.5%). Median maximum quantity of morphine used per day was 35 mg (range 0-150 mg). CONCLUSIONS: Use of a systematic pain control program may improve compliance with CRT.

Outcomes in patients with early-stage hypopharyngeal cancer treated with radiotherapy.

PURPOSE: To analyze the outcome in patients with early-stage hypopharyngeal cancer (HPC) who were treated with radiotherapy (RT). METHODS AND MATERIALS: Between February 1988 and February 2007, 77 patients with Stage I or Stage II HPC underwent definitive RT in the Division of Radiation Oncology at the National Cancer Center Hospital. Eleven of the patients received local irradiation, and the other 66 patients received elective bilateral neck irradiation and booster irradiation to the primary lesion. The median follow-up period for all the patients was 33 months from the start of RT, ranging from 3 to 229 months. RESULTS: The rates of overall survival, HPC-specific survival, HPC recurrence-free survival, and local control with laryngeal voice preservation for the 77 patients at 5 years were 47%, 74%, 57%, and 70%, respectively. The survival rates were not affected by the patient characteristics or treatment factors, but the RT field was significantly correlated with local control in a multivariate analysis. Seven of the patients had Grade 3 or greater complications, but these complications occurred after salvage surgery in 6 of the patients. Of the 77 patients, 83% had synchronous or metachronous malignancies, but these malignancies did not influence the survival of the patients if the malignancies were detected at an early stage. CONCLUSION: RT is an appropriate treatment method for early-stage HPC. However, because synchronous or metachronous malignancies occur at a relatively high frequency, careful follow-up and the early detection of such malignancies are critical.

Metastases to the lingual nodes in tongue cancer: a pitfall in a conventional neck dissection.

Some classical textbooks of anatomy provided a detailed description of the lingual nodes, which are small inconstant lymph nodes in the floor-of-mouth and the upper neck. The clinical importance of these lymph nodes in cancer therapy, however, has been underestimated so far. We previously reported an extremely poor prognosis of oral tongue cancer patients who had lesions at the root of the lingual artery and assumed that metastases in occult lingual nodes might be responsible for such lesions. This case report clearly demonstrates the distinctive draining course of the lateral lingual nodes, which may potentially be left untreated by a neck dissection. A 63-year-old Japanese male with T2 squamous cell carcinoma of the oral tongue showed multiple metastatic involvements of the lateral lingual nodes; three nodes in close contact with the sublingual gland, and one node at the root of the lingual artery. A systematic inspection of lymph nodes along the draining course of the lateral lingual nodes should be included, because a neck dissection in continuity with the primary tumor (a pull-through approach) is still inadequate for the removal of the lymph nodes at the root of the lingual artery.

Metastatic neck disease beyond the limits of a neck dissection: attention to the 'para-hyoid' area in T1/2 oral tongue cancer.

OBJECTIVE: We evaluated patients with small oral tongue cancer suffering from recurrence, which develops in the intervening area between the primary site and the neck. Lesions in the area around the cornu of the hyoid bone ('para-hyoid' area) often involve the hypoglossal nerve and the root of the lingual artery, resulting in treatment failure and death. METHODS: A 10-year retrospective chart review was conducted of 248 oral tongue cancer patients with small primary tumors (T1/2). No patients who underwent postoperative radiotherapy (PORT) were included. RESULTS: After excluding those who had local failure or developed new primary lesions, 6.3% of the patients were noted to have a para-hyoid lesion. A similar incidence was observed between the patients with and without previous neck dissection, 6.9% and 5.7%, respectively. All but one patient died due to uncontrolled neck disease. CONCLUSIONS: Recurrent para-hyoid lesions could occur, irrespective of a previous neck dissection. In other words, the para-hyoid area is beyond the limits of a neck dissection. Once a para-hyoid lesion becomes clinically evident, it seems difficult to salvage. Therefore, a careful inspection of the area should be included intraoperatively in any type of neck dissection (i.e. elective or therapeutic) for patients with oral tongue cancer. This may be the key to improving the regional control rate of patients with small oral tongue cancer. We believe that some patients will benefit from more aggressive treatment of the neck, although PORT seems unnecessary for the majority of the patients with limited neck disease.

Mucoepidermoid carcinoma of the thyroid gland showing marked ciliation suggestive of its pathogenesis.

Mucoepidermoid carcinoma of the thyroid gland is a rare tumor first described by Rhatigan et al. in 1977. Its pathogenesis is still controversial. With regard to its most likely origin, some authors have suggested that it arises directly from follicular epithelium whereas others have proposed that it arises from ultimobranchial body (diverticulum from the fourth pharyngeal pouch) remnants, also known as solid cell nests (SCN). Herein is reported a unique case of thyroid mucoepidermoid carcinoma. The patient, a 67-year-old man, presented with a non-tender thyroid mass and vocal cord fixation. The tumor was poorly defined, necessitating subtotal thyroidectomy with composite resection of the adjacent structures. Pathologically, the tumor cells had characteristics of mucoepidermoid carcinoma, along with layers of columnar cells showing marked ciliation resembling respiratory-type epithelium, suggesting that this rare tumor had originated from SCN. p63 immunopositivity in the tumor provided additional evidence for the pathogenesis.

Clinicopathological factors related to cervical lymph node metastasis in a patient with carcinoma of the oral floor.

CONCLUSION: Tumors developing into the muscle layer and tumor thickness > or =5 mm are the most important risk factors associated with nodal metastasis. OBJECTIVE: It is necessary to identify the risk factors associated with cervical metastasis in patients with oral floor cancer to reveal the role of elective neck dissection for oral floor cancer. PATIENTS AND METHODS: Forty-eight patients with oral floor cancer were retrospectively analyzed for a correlation between clinicopathologic factors and cervical lymph node metastasis using Fisher's exact test and a logistic regression test. RESULTS: Univariate analysis showed significantly positive correlations for growth type, mitosis, perineural invasion, vascular invasion, lymphatic invasion, depth, thickness, and infiltration growth ratio. Multivariate analysis had a significantly positive correlation with nest formation and depth in all patients, and with thickness in patients with T1 or T2. In patients with bilateral cervical lymph node metastasis, lymph node metastasis was significantly positively correlated with perineural invasion.

Prognostic factors for hypopharyngeal cancer: a univariate and multivariate study of 142 cases.

CONCLUSIONS: Reduction of distant metastases is essential for better survival. Effective adjuvant chemotherapy should be developed for patients with advanced primary disease (T>2) as well as for patients with advanced nodal status (N>0 or PLN>2). OBJECTIVES: The aim of this study was to identify prognostic factors for hypopharyngeal cancer. PATIENTS AND METHODS: In all, 142 previously untreated patients were analyzed retrospectively; 75% of the cases were stage III or IV. Surgical resection was administered as primary treatment to 116 of the patients (82%), while 26 patients (18%) underwent primary radiotherapy. RESULTS: The cause-specific 5-year actuarial survival was 46.3%. Distant metastases were the most frequent (23%) cause of failure, followed by local recurrence (15%), and regional recurrence (13%). Cox's regression analysis showed that the significant factors affecting cause-specific survival were N classification, T classification, number of pathological lymph node metastases (PLN), lymphatic invasion, and positive surgical margin. Similarly, T classification and PLN affected distant metastases.

[Botulinum toxin injection into the cricopharyngeal muscle for dysphagia: report of 2 successful cases].

Dysphagia is frequently observed in patients with sequelae after multiple cerebral infarctions and those with neuromyopathy. Dysphagia in these patients can be successfully treated by laryngeal suspension and cricopharyngeal myotomy. Surgery is not indicated in senile patients with serious complications, where conservative treatment is performed. We injected botulinum toxin into the right cricopharyngeal muscle with excellent results in two dysphagic patients with multiple cerebral infarction who refused surgery. There two cases developed dysphasia after multiple cerebral infarction, where surgical therapy was not indicated. Dysphagia is successfully treated by 5 units of botulinum toxin injected into the cricopharyngeal muscle. Botulinum toxin injection is considered useful for dysphagia in patients in whom surgery is not indicated. The effect of botulinum toxin lasts for 3 to 4 months. Injection of botulinum toxin is useful for patients with temporary dysphasia after cerebral infarction and soon improves swallowing with the assistance of rehabilitation.

Results of multimodality therapy for squamous cell carcinoma of maxillary sinus.

BACKGROUND: A wide variety of modalities, including surgery, radiation therapy, and chemotherapy, alone or in combination, have been used for the treatment of squamous cell carcinoma (SCC) of the maxillary sinus to obtain better local control and maintain functions. However, there is still much controversy with regard to the optimum treatment. METHODS: From 1987 to 1999, 33 patients with SCC of maxillary sinus were treated at the Department of Otolaryngology-Head and Neck Surgery, University of Tokyo Hospital. The treatment consisted of 30-40 grays (Gy) of preoperative radiotherapy with concomitant intraarterial infusion of 5-fluorouracil and cisplatin followed by surgery and 30-40 Gy of postoperative radiotherapy, for tumors without skull base invasion. For tumors invading the skull base, preoperative systemic chemotherapy with or without radiotherapy was performed, instead of intraarterial chemotherapy, then followed by skull base surgery. The surgical procedures varied according to the extent of tumor. Results were compared with those of the 108 patients treated in our hospital from 1976 to 1982. RESULTS: Partial maxillectomy was performed in 2 T2 patients and 12 T3 patients. Total maxillectomy was performed in 1 T2 patient, 3 T2 patients, and 7 T4 patients. Skull base surgery was performed in eight T4 patients. Orbital content and hard palate were preserved in 22 patients and 18 patients, respectively. The overall 5-year survival rates were 86% in T 3 patients and 67 % in T4 patients, respectively. CONCLUSIONS: Our multimodal treatment has provided favorable local control and survival outcome with good functional results.