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.

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.

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.

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.

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.

The effect of Japanese cedar-specific immunotherapy on cytokine production in peripheral blood mononuclear cells.

The most common cause of seasonal allergic rhinitis in Japan is the Japanese cedar (JC). Recently, a pullulan-conjugated antigen (CS-560) has been developed to reduce adverse effects and to enhance the effect of JC-specific immunotherapy (IT). If the mechanism of IT can be fully elucidated and the treatment can be used safely and with specificity, IT should be reconsidered as a superior treatment for JC pollinosis. Thirteen patients with JC pollinosis who received IT were compared to 10 patients who did not receive IT. All patients were followed through two pollen seasons by means of allergy diaries. Peripheral blood mononuclear cells (PBMC) were collected before IT and just before each pollen season, and these were stimulated with pollen extract. The concentrations of IL-4, IL-5, IL-13 and IFN-gamma in the culture supernatants were determined using an ELISA. Furthermore, messenger (m)RNA expressions of IL-4 and IL-5 from cultured PBMC were also studied. As a result of the allergy diaries, we confirmed the clinical efficacy of CS-560. The symptom-medication scores were significantly decreased by IT. The levels of IL-4, IL-5 and IL-13 declined only in the IT group. However, the level of IFN-gamma did not change in either group. IL-4 and IL-5 mRNA expressions were inhibited in the IT group compared to that in the non-IT group. In conclusion, specific IT for JC pollinosis using CS-560 clearly modified cytokine expression by PBMC.

[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.

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.

Two types of direction-changing positional nystagmus with neutral points.

OBJECTIVES: We encountered patients who had static direction-changing positional nystagmus (DCPN) canceled at about 20-30° yaw head rotation from the supine position. This nystagmus was also canceled when the head was rotated 180° from this position. We termed these head positions neutral points. The positional nystagmus observed (except at the neutral points) was thought to occur due to a "heavy cupula" or "light cupula". The purpose of this study was to examine DCPN with neutral points as well as the pathomechanism of this condition. METHODS: Retrospective case review of patients attending two hospitals. Sixteen patients who exhibited DCPN with neutral points were examined using an infrared camera (installed in goggles). Using this system, the vestibulo-ocular reflex (VOR) was recorded, and VOR gain was obtained. Vestibular function and the affected side were determined. In addition, the angle between the supine position and neutral point was measured in each patient. We also examined other positional nystagmus occurring at other times. RESULTS: In the heavy cupula type group, we noted positional nystagmus for which repositioning maneuvers were successful, whereas, in the light cupula type group, repositioning maneuvers were not effective. The angle between supine position and neutral point was 26.5 ± 11.6°. CONCLUSIONS: Heavy cupula type may occur as a result of otoconia while light cupula type may be due to the specific gravity of the endolymph. The VOR gain and side of the benign paroxysmal positional vertigo (BPPV) observed suggested that the affected side was that to which the neutral point was deviated.

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.

Aberrant internal carotid artery in the middle ear with a deficiency in the origin of the anterior cerebral artery: a case report.

An aberrant internal carotid artery (ICA) in the middle ear is rare and difficult to diagnose, and may lead to severe complications. We present here a case of aberrant ICA with a deficiency in the origin of the anterior cerebral artery. The only symptom was aural fullness, and a nonpulsatile and white tympanic mass in the anteroinferior area was noted. Computed tomography (CT) and magnetic resonance angiography (MRA) are useful tools that provide excellent visualization of the temporal bone for the diagnosis of aberrant ICA by the following features: intratympanic mass, enlarged inferior tympanic canaliculus, absence of the vertical segment of the ICA canal, and absence of bone covering the tympanic portion of the ICA. In addition, in this case, a deficiency in the origin of the anterior cerebral artery on the same side was identified by MRA, and cerebral arteriography and a carotid occlusion test were performed. Because of the deficiency in the origin of the anterior cerebral artery, the ICA compression revealed that there was almost no cross flow from the other ICA. Our experience illustrates that after confirmation of the diagnosis of aberrant ICA, localized treatment and/or surgical procedures should be considered carefully.

Neuroaspergillosis in an immunocompetent patient successfully treated with voriconazole and a corticosteroid.

Aspergillosis of the central nervous system (CNS) is an uncommon infection, mainly occurring in immunocompromised patients. We report a case of nasocerebral aspergillosis in an immunocompetent patient successfully treated with voriconazole and a corticosteroid. Magnetic resonance imaging (MRI) showed contrast enhancement surrounding the brainstem and cerebellum with intramedullary pontine and cerebellar T2-hyperintense lesions. The patient's symptoms and MRI abnormalities improved after voriconazole and corticosteroid treatment; however, discontinuation of the corticosteroid caused a worsening of the T2-hyperintense lesions, whereas resuming it resulted in its improvement. This suggested that these T2-hyperintense lesions may be due to secondary inflammation caused by aspergillosis and not the aspergillosis itself. We conclude that treatment with a combination of voriconazole and a corticosteroid appears to be effective for the treatment of some patients with CNS aspergillosis.

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.

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.

Positional nystagmus showing neutral points.

We encountered patients who had their static direction-changing positional nystagmus canceled at about 20-30 degrees yaw head rotation from the supine position. This nystagmus was also canceled when the head was rotated 180 degrees from this position. We call these head positions neutral points. At the neutral points, the cupula of the horizontal semicircular canal of the affected ear is positioned vertical to the gravitational plane and no deflection of the cupula occurs. The positional nystagmus observed (except the neutral points) was thought to occur due to a "heavy cupula" or "light cupula", which may be determined by the specific gravity of its endolymph.

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.

Combined effects of nitrous oxide and propofol on the dynamic cerebrovascular response to step changes in end-tidal PCO2 in humans.

BACKGROUND: Nitrous oxide (N2O) and propofol exhibit directionally opposite effects on the cerebral circulation, vasodilation and vasoconstriction, respectively. The authors investigated an interaction between the two anesthetic agents on the dynamic cerebrovascular response to step changes in end-tidal pressure of carbon dioxide (PetCO2) in humans. METHODS: Participants with no systemic diseases were allocated into two groups, each of which was anesthetized sequentially with two protocols. Patients in group 1 were anesthetized with 30% O2 + 70% N2O. A continuous intravenous infusion of propofol (7-10 mg x kg(-1) x h(-1)) was then added to the N2O. Patients in group 2 were anesthetized first with continuous infusion of propofol (10 mg x kg(-1) h(-1)), and then 30% O2 + 70% N2O was added to the propofol anesthesia. Using transcranial Doppler ultrasonography, blood flow velocity at the middle cerebral artery (FV(MCA)) was measured during a step increase (on-response) followed by a step decrease (off-response) in PetCO2, with PetCO2 ranging between approximately 28 and 50 mmHg. The dynamic FV(MCA)-PetCO2 relationship was analyzed using a mathematical model that was characterized with a pure time delay, and a time constant and a gain each for the on- or off-response. RESULTS: The addition of propofol to the N2O anesthesia increased the on-response time constant (P < 0.01), whereas the addition of N2O to the propofol anesthesia increased the time constants for on- (P < 0.01) and off-responses (P < 0.05). However, the addition of either anesthetic did not affect the gains. CONCLUSIONS: Propofol and N2O, when one is added to the other, produce similar dynamic FV(MCA) responses to sudden changes in PetCO2. Addition of each anesthetic slows the dynamic response and produces the response whose magnitude is proportional to the baseline FV(MCA).

Analysis of natural history of Japanese cedar pollinosis.

BACKGROUND: The marked increase in the incidence of Japanese cedar (Cryptomeria japonica; JC) pollinosis is a social problem in Japan. Elucidation of its natural history is, therefore, essential. METHODS: Cross-sectional and vertical-sectional studies were performed regarding the effects of aging on sensitization to Japanese cedar pollen (JCP) and development of JC pollinosis by measuring serum IgE titers to JCP and by oral examination of residents of the Maruyama Town, Chiba, Japan from 1995 to 2001. We also studied the incidence of its spontaneous remission and the background factors. RESULTS: In a vertical-sectional study, the serum IgE titer to JCP was strongly influenced by the amounts of pollen scattered. An increase in age by 6 years did not reduce the IgE titer to JCP in subjects in their 40s. However, in subjects aged 60 or more, annual differences in the JCP count did not affect serum IgE titer to JCP, which remained low even after a season with a high pollen count. In subjects with JC pollinosis aged over 40 showing a CAP RAST score of more than 2 to JCP in 1995, spontaneous remission of JC pollinosis was observed in 16.1% over a period of 6 years. Factors affecting spontaneous remission include sex, age at the time, serum IgE titer to JCP and age at first onset of JC pollinosis. CONCLUSIONS: The CAP RAST score was strongly associated with spontaneous remission in the multivariable model.