Independent exercise for glottal incompetence to improve vocal problems and prevent aspiration pneumonia in the elderly: a randomized controlled trial.

OBJECTIVES: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. DESIGN: Parallel-arm, individual randomized controlled trial. METHODS: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. RESULTS: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). CONCLUSION: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. CLINICAL TRIAL: gov Identifier-UMIN000015567.

Intraoperative photodynamic detection of normal parathyroid glands using 5-aminolevulinic acid.

OBJECTIVE: It is important to identify and save the normal parathyroid glands during head and neck surgery because of their role in regulating the blood calcium level, yet it is often difficult to localize normal parathyroid glands during surgery. Fluorescence-guided parathyroidectomy in patients with hyperparathyroidism has already proved useful. However, there are few reports of fluorescence-guided localization of normal parathyroid glands in humans. We investigated the utility of fluorescence-guided localization of normal parathyroid glands during thyroidectomy and completed a spectral fluorescence analysis of the accumulation of 5-aminolevulinic acid metabolites in the parathyroid glands. METHODS: Eight patients with benign thyroid disease and five with malignant thyroid tumors were given 20 mg/kg body weight of 5-aminolevulinic acid orally 5 hours before surgery. After the posterior surface of the thyroid gland was exposed and the recurrent laryngeal nerve was identified, we illuminated the area with a violet-blue light of 405 nm. Tissues showing red fluorescence were biopsied to analyze the spectral fluorescence. RESULTS: Under the violet-blue light, normal parathyroid glands showed red fluorescence, while the surrounding structures such as the thyroid gland, muscles, and fat remained nonfluorescent. The spectral peak was observed at 635 nm indicating 5-aminolevulinic acid metabolites. Histopathologically, the biopsied tissue corresponded to normal parathyroid glands. CONCLUSIONS: 5-Aminolevulinic acid is useful to localize the normal parathyroid glands during thyroid surgery in humans.

Diagnosis and therapy for an extracranial carotid aneurysm.

OBJECTIVE: To describe the diagnostic means and therapy employed in three cases of extracranial carotid aneurysms. METHODS: Retrospective analysis of three cases. RESULTS: For the diagnosis we obtained real-time pictures of each aneurysm by color Doppler ultrasonography before the angiography. Based on the result of cerebral collateral flow evaluation, ligation of both ends of the aneurysm was performed in one case, embolization of the artery in another, and resection of the aneurysm in the other; vascular reconstruction was not necessary. Although a carotid artery balloon occlusion test must be done before the operation, color Doppler ultrasonography and/or a transcranial color Doppler-guided Matas' test were performed instead, because these patients needed immediate management. CONCLUSION: The diagnostic procedures were very useful to decide what action to take in such urgent cases.

Malignant lymphoma arising from heterotopic Warthin's tumor in the neck: case report and review of the literature.

Warthin's tumor (WT), so-called adenolymphoma, is a benign salivary gland tumor with both epithelial and lymphoid histological characteristics, so the histogenesis remains unclear. Treatment consists primarily of tumor removal or conservative follow up. Here we present a rare case of malignant lymphoma arising from heterotopic (ectopic) WT. A 102-year-old man presented with a mass in the left side of the neck which was painless but gradually enlarged over 1 month. The mass was 2-3 cm in diameter, and freely moveable below the angle of the mandible. The mass was totally removed. The histological diagnosis was malignant lymphoma, diffuse large B-cell type, arising from heterotopic WT. Postoperative staging examination including chest radiography, bone scan, and computed tomography of the abdomen and pelvis revealed no evidence of dissemination of malignant lymphoma. Malignant transformation within WT is rarer in the lymphoid component than in the epithelial component. Only 16 cases of malignant transformation arising from WT have been reported, including only three cases of non-Hodgkin lymphoma apparently arising from heterotopic WT. Tumor removal or careful follow up is recommended in patients with WT because of the potential risk posed by such malignant transformation.

WISP-2 expression in human salivary gland tumors.

This study was designed to disclose detailed genetic mechanisms in salivary gland tumors (SGTs) for development of novel independent marker. We constructed an in-house cDNA microarray carrying 2,201 cDNA clones derived from SGT and oral squamous cell carcinoma cDNA libraries. Four cell lines that originated from the SGT-derived cell lines were analyzed using this microarray system. The genes identified by our microarray system were further analyzed at the mRNA or protein expression level in other types of human cancer cell lines and clinical samples (ten normal salivary glands [NSGs], eleven pleomorphic adenomas, ten adenoid cystic carcinomas and three adenocarcinomas). Two up-regulated genes and six down-regulated genes were identified in common when compared with the control RNA. Of the up-regulated genes, WISP-2, which plays an important role in breast carcinogenesis, was selected for further analyses. We found a higher expression of the WISP-2 gene in the SGT-derived cell lines compared with other types of human cancer cell lines. Furthermore, WISP-2 mRNA and protein expression levels in NSGs were significantly higher than those in SGTs. These results suggest that WISP-2 could be a reliable independent marker and that down-regulation or loss of the WISP-2 gene may be associated with the development of SGTs.

Protein expression profiling identifies maspin and stathmin as potential biomarkers of adenoid cystic carcinoma of the salivary glands.

Adenoid cystic carcinoma (ACC) is one of the most common malignant tumors of the salivary glands. It tends to grow slowly but is associated with a poor prognosis compared to other malignant salivary gland tumors. To identify specific markers of ACC, we examined protein expression profiling in ACC xenograft and normal salivary glands (NSG) using fluorescent 2-dimensional differential in-gel electrophoresis (2-D-DIGE), an emerging technique for comparative proteomics, that improves the reproducibility and reliability of differential protein expression analysis between the samples. To identify the proteins, matrix-assisted laser desorption/ionization time-of-flight peptide mass fingerprinting was carried out. Using these strategies, we detected 4 upregulated proteins and 5 downregulated proteins in ACC xenograft. Maspin and stathmin were selected for further analyses. Western blotting and immunohistochemical staining showed a higher expression of these proteins in ACC xenograft and clinical ACC tissue compared to NSG. Furthermore, Expression of these proteins was correlated with the histologic grading of ACC (n = 10). Therefore, our data indicate that maspin and stathmin may be not only useful biomarkers of ACC but also markers of biologic behavior in this tumor.

Identification of candidate genes associated with salivary adenoid cystic carcinomas using combined comparative genomic hybridization and oligonucleotide microarray analyses.

Adenoid cystic carcinoma (ACC) of the salivary gland often has a variable clinical course with a poor prognosis. To investigate DNA copy number aberrations associated with ACCs, we compared comparative genome hybridization data from ACCs (n = 6) with other types of salivary gland tumors such as adenocarcinomas (n = 3) and pleomorphic adenomas (n = 6). While 15 gain loci (1q32, 6p25, 6q21-q24, 7q11.2, 7q31, 10q11.2, 11p12-q12, 12q13, 12q14, 13q24, 16p13.3-13.2, 18p11.3, 18q23, 19q13.4, and Xq28) were detected, no DNA loss locus was evident. To examine the expression status of genes on the ACC-associated loci, transcriptional measurements of approximately 38000 human genes then were monitored using Affymetrix U133 Plus 2.0 GeneChips. A total of 4431 genes were found differentially expressed by at least two-fold between ACCs and normal salivary glands. Of them, 3162 genes were up-regulated and 1269 genes were down-regulated in ACCs. After obtaining locus information about the RNA transcripts from the Affymetrix database, we found 262 ACC-associated genes with increased expression on ACC-associated loci. To investigate functional network and gene ontology, the 262 genes were analyzed using Ingenuity Pathway Analysis Tool. The function with the highest P value was a cancer-related function (P = 2.52e-4 to 4.71e-2). In addition, we identified pituitary tumor-transforming gene 1 and transformation related protein 63 genes that were up-regulated by increasing DNA copy number and modulated expression of oncogenes. These results suggested that the combination of copy number and gene expression profiling provides an improved strategy for gene identification in salivary gland ACCs.

Thyroid cancer with massive invasion into the neck and mediastinal great veins.

Papillary thyroid carcinoma with massive invasion into the great veins of the neck and mediastinum has rarely been reported and is thought to have a poor prognosis. Here we report successful management of a case of papillary thyroid carcinoma with extensive invasion into the left internal jugular vein, left brachiocephalic vein, and superior vena cava, followed by reconstruction of the superior vena cava using an artificial graft. The operation was conducted to prevent sudden death due to complete obstruction of venous flow, improve the patient's quality of life, and prolong survival. The patient has survived for more than two years after surgery, with good general condition.

[Malignant mixed tumor].

The term "malignant mixed tumor" is usually synonymous with "carcinoma in pleomorphic adenoma," a secondary carcinoma developing in pre-existing pleomorphic adenoma. However, it sometimes indicates a group of tumors consisting of carcinoma in pleomorphic adenoma, carcinosarcoma (true malignant mixed tumor) and metastasizing benign mixed tumor, the latter 2 being the most infrequent. According to the data of the Japanese committee on TNM classification for salivary gland carcinomas, carcinoma in pleomorphic adenoma accounted for about 10% of all salivary gland carcinomas, both in the parotid and submandibular glands. The main type of carcinomas arising in pleomorphic adenoma were undifferentiated carcinoma, adenocarcinoma and squamous cell carcinoma. Crude 5- and 10-year survival rates were 54.7% and 42.7%, respectively. Invasive carcinomas and carcinomas of high grade malignancy carried worse prognoses. The treatment of choice for carcinoma in pleomorphic adenoma has consisted of en-bloc excision with wide margin. Invasive growth, facial nerve involvement, lymph node metastasis or high-grade malignant tumor are grounds for postoperative radiation therapy. The role of chemotherapy has not yet been well established.

Preoperative radiation therapy for carcinoma of the oropharynx: prognostic factors for locoregional control and survival.

BACKGROUND: To assess the role of preoperative irradiation and surgery in patients with oropharyneal cancer. MATERIALS AND METHODS: Seventy-five patients were treated with radiotherapy alone or followed by surgery. The stage distribution was stage II in 15 patients, stage III in 16 patients, stage IVA in 38 patients and stage IVB in 6 patients. RESULTS: Thirty-five patients were treated with radiotherapy alone and the remaining 40 underwent definitive surgery after radiation therapy. In the multivariate analysis, both good Karnofsky Performance Status (KPS) and complete response (CR) after radiation therapy had positive impact on locoregional control and survival. Overall survival at 5 years was 65% and 20% for KPS > or = 90% and KPS < 90%, respectively (p < 0.0001). Corresponding values for CR and non-CR were 80% and 35%, respectively (p = 0.0001). CONCLUSION: The results indicated that the KPS and complete response after radiation therapy were very sensitive surrogates for locoregional control and survival for cancer of the oropharynx.

Ipsilateral full-thickness forearm skin graft for covering the radial forearm flap donor site.

OBJECTIVES/HYPOTHESIS: The technique of the ipsilateral full-thickness forearm skin graft for covering the defect of radial forearm free flap (RFFF) improves aesthetic impairment at the recipient and donor sites by split-thickness skin graft repair and omits the need to make an extraoperative site for harvesting the skin graft. However, in this technique, the RFFF is limited in size. In the present study, we considered a model of the forearm and calculated the possible size of the RFFF for using this technique. METHODS: The calculation was conducted under assumptions that the isosceles-triangle skin graft is elevated as its height is twice the RFFF length in the direction of the forearm axis and that the forearm skin defect can be primarily closed with a width shorter than one-fourth of the wrist circumference. The calculation revealed that this technique is feasible when the RFFF width, that is, the length vertical to the forearm axis, is shorter than half of the wrist circumference. We repaired the RFFF defect using this technique in 15 patients with head and neck cancer in whom the RFFF size conformed to the above-mentioned condition. RESULTS: When the RFFF width was shorter than half of the wrist circumference and the isosceles-triangle skin graft was elevated as its height was twice the RFFF length, the RFFF defect could be repaired using this technique in all 15 patients. CONCLUSION: The above-mentioned condition (that the RFFF width is shorter than half of the wrist circumference) is useful for determining whether or not the technique of ipsilateral full-thickness forearm skin graft can be used for covering the RFFF defect.

State of mastication affects quality of life in patients with maxillary sinus cancer.

OBJECTIVES/HYPOTHESIS: The quality of life of head and neck cancer patients after treatment is poor compared with a typical population sample. However, little is known about patients with maxillary sinus cancer. The identification of symptoms that are most troublesome for these patients and the development of strategies to minimize these negative sequelae should be matters of high priority. STUDY DESIGN: A restrospective study of patients with maxillary sinus cancer who underwent maxillary bone resection. METHODS: Thirty patients with maxillary sinus squamous cell carcinoma participated in the study. The relationships among the degree of masticatory ability, the extent of the surgically resected area, and quality of life after combined treatment of maxillary cancer were evaluated. RESULTS: Scores of all physical and mental factors as assessed by the Short Form-36 questionnaire decreased as the masticatory ability of patients worsened. In edentulous cases, the masticatory ability was higher in the reduced operation group than in the extensive operation group. CONCLUSION: Maintaining adaptability to a denture is essential to preserve quality of life, particularly in patients with anodontia.

Usefulness of diagnostic imaging in primary hyperparathyroidism.

BACKGROUND: In patients with primary hyperparathyroidism, prevention of urinary stone recurrence can be achieved by surgical removal of the enlarged parathyroid gland. To ensure the efficacy of surgery for primary hyperparathyroidism, preoperative localization of the enlarged gland is important. In the present study, usefulness of diagnostic imaging for localization of the enlarged gland was investigated in primary hyperparathyroidism. METHODS: We retrospectively examined the findings of imaging studies and clinical records in 79 patients (97 glands) who underwent surgical treatment for primary hyperparathyroidism at Chiba University Hospital between 1976 and 2000. The detection rates of accurate localization were investigated for imaging techniques, such as ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), thallium-201 and technetium-99m pertechnetate (Tl-Tc) subtraction scintigraphy and 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy, and analysed in relation to the size and weight of the gland and pathological diagnosis. RESULTS: The detection rates by US, CT, MRI, Tl-Tc subtraction scintigraphy and MIBI scintigraphy were 70%, 67%, 73%, 38% and 78%, respectively. The overall detection rate changed from 50% to 88% before and after 1987. The detection rate of MIBI scintigraphy was superior to Tl-Tc subtraction scintigraphy. CONCLUSION: In primary hyperparathyroidism, improvement of accurate localization of an enlarged parathyroid gland was demonstrated along with recent advances in imaging techniques including MIBI scintigraphy.

Interleukin-13 induces thymus and activation-regulated chemokine (CCL17) in human peripheral blood mononuclear cells.

BACKGROUND: In allergic inflammation involving allergic rhinitis, the predominance of Th(2) lymphocytes is one of the primary causal agents in promotion of the allergic condition. Thymus and activation-regulated chemokine (TARC/CCL17) is a recently identified chemokine that induces the development of Th(2) lymphocytes. One of the sources of TARC has been reported to be peripheral blood mononuclear cells (PBMCs). OBJECTIVE: We investigated TARC production from PBMCs by the stimulation of specific antigens and Th(2) type cytokines. METHOD: PBMCs were isolated from both allergic rhinitis patients and healthy volunteers. PBMCs were incubated with cytokine. TARC mRNA expression was examined by real time PCR methods and the amount of TARC production was examined by ELISA. RESULTS: IL-13 was found to be the most potent inducer for TARC mRNA expression and protein production in PBMCs. Furthermore, tumour necrosis factor alpha and IL-13 synergistically induce TARC. The amount of TARC from allergic rhinitis patients was significantly larger than that from healthy volunteers. Moreover, TARC was induced by a specific antigen, and was 35% inhibited by an anti-IL-13 neutralizing antibody. CONCLUSION: These results indicate that IL-13 is important in TARC mediated Th(2) lymphocytes infiltration in the nasal mucosa.

Hemodynamic changes of the hand after radial forearm flap harvesting.

After radial forearm flap harvesting, there is some risk for hand circulatory disorders. To reveal the changes in circulatory dynamics in the hand after harvesting this flap, the authors compared blood pressure and flow by color Doppler ultrasonography in the donor and nondonor hands, and evaluated the long-term changes in these factors in 40 patients undergoing this operation. Blood pressure and flow of the index finger in the donor hands were lower than those in the nondonor hands during the first 2 months postoperatively, but they virtually returned to the level of those in the nondonor hands within 1 year of the operation. These results suggest that after harvesting the radial artery, collateral circulation in the hand developed during a short postoperative period. Therefore, the authors can predict the long-term safety of forearm flap harvesting by evaluating the hemodynamic changes of the digits caused by acute occlusion of the radial artery preoperatively, which would reflect the hemodynamics at an early postoperative stage.

Usefulness of color Doppler sonography for assessing hemodynamics of free flaps for head and neck reconstruction.

This report focuses on the monitoring of intraoperative and postoperative hemodynamics of free flaps for repair of head and neck defects by color Doppler sonography (CDS). The study group included 20 patients with head and neck cancer who underwent resection and reconstruction with free flaps. The hemodynamics in the feeding arteries of the flaps were measured during the following six stages: before surgery, immediately after microvascular anastomosis, and on postoperative days 1, 3, 5, and 7. The pulsatility index (PI) was used as the index for measuring changes in hemodynamics over time. Grafts showed the maximal PI immediately after vascular anastomosis. PI decreased over 3 to 7 days. Of the 20 patients, 1 patient in whom the hypopharynx was reconstructed with the radial forearm flap developed venous occlusion. This was diagnosed during the early stage using CDS, allowing the flap to be saved. CDS proved to be very useful for real-time observation of the hemodynamics in free flaps.