Targeting Anterior Commissure Involvement with Hyperfractionated Radiotherapy for T1-T2 Squamous Cell Carcinoma of the Glottic Larynx.

Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1-T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation.

FDG-PET findings of Ameloblastoma: a case report.

INTRODUCTION: Ameloblastoma is a benign odontogenic neoplasm of the jaw, rarely presenting as a malignant tumor. Although it is very important to discriminate ameloblastoma from ameloblastic carcinoma in order to decide the appropriate operative procedure, this is difficult using conventional CT and MRI. CASE DESCRIPTIONS: We report a case of maxillar ameloblastoma in a 78-year-old man where FDG-PET/CT was useful for making this discrimination. CT demonstrated a 31 × 43 × 46-mm mass in the left posterior maxillary sinus with destruction of its posterior and lateral wall and alveolar bone. MRI demonstrated a hypo- to isointense heterogeneous pattern on T1WI, heterogeneous hyperintensity with a prominent high-signal spot on T2WI, high signal intensity on DWI reflecting restricted diffusion, and strong heterogeneous enhancement. Because FDG-PET/CT showed mild FDG uptake (SUVmax 2.40) by the mass, ameloblastoma, rather than ameloblastic carcinoma, was considered to be the correct diagnosis. DISCUSSION AND EVALUATION: It appears that ameloblastic carcinoma shows intense FDG uptake, whereas ameloblastoma shows mild or moderate FDG uptake, and only rarely intense FDG uptake. Our experience suggests that FDG-PET/CT may be effective for discriminating ameloblastoma from ameloblastic carcinoma. Especially, in cases showing mild FDG uptake, benign ameloblastoma would seem the most likely diagnosis. CONCLUSIONS: FDG-PET/CT may be useful as an adjunctive modality for diagnosis, treatment planning and surveillance of ameloblastoma and ameloblastic carcinoma.

Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa.

Although type 2 immune responses to environmental Ags are thought to play pivotal roles in asthma and allergic airway diseases, the immunological mechanisms that initiate the responses are largely unknown. Many allergens have biologic activities, including enzymatic activities and abilities to engage innate pattern-recognition receptors such as TLR4. In this article, we report that IL-33 and thymic stromal lymphopoietin were produced quickly in the lungs of naive mice exposed to cysteine proteases, such as bromelain and papain, as a model for allergens. IL-33 and thymic stromal lymphopoietin sensitized naive animals to an innocuous airway Ag OVA, which resulted in production of type 2 cytokines and IgE Ab, and eosinophilic airway inflammation when mice were challenged with the same Ag. Importantly, upon exposure to proteases, uric acid (UA) was rapidly released into the airway lumen, and removal of this endogenous UA by uricase prevented type 2 immune responses. UA promoted secretion of IL-33 by airway epithelial cells in vitro, and administration of UA into the airways of naive animals induced extracellular release of IL-33, followed by both innate and adaptive type 2 immune responses in vivo. Finally, a potent UA synthesis inhibitor, febuxostat, mitigated asthma phenotypes that were caused by repeated exposure to natural airborne allergens. These findings provide mechanistic insights into the development of type 2 immunity to airborne allergens and recognize airway UA as a key player that regulates the process in respiratory mucosa.

Pro-resolution mediator lipoxin A4 and its receptor in upper airway inflammation.

OBJECTIVES: The resolution of inflammation is an active process controlled by several anti-inflammatory and pro-resolution mediators. Lipoxin A4, an endogenous lipid mediator, is a potential pro-resolution mediator that could attenuate inflammation. This study was conducted to elucidate the role of lipoxin A4 in upper airway inflammation. METHODS: Nasal secretions were collected from patients with chronic rhinosinusitis with nasal polyposis, patients with allergic rhinitis, and control subjects. The concentration of lipoxin A4 was measured by enzyme-linked immunosorbent assay. Nasal tissues were obtained from nasal polyps and inferior turbinates during endonasal surgery. The mRNA expressions of lipoxygenases (LOXs), lipoxin receptor (formyl peptide receptor-like 1; FPRL-1), and cysteinyl leukotriene type 1 receptor (CysLT1R) in nasal tissues were examined by reverse-transcription polymerase chain reaction. Tissue localization of FPRL-1 was determined by immunohistochemical staining. The in vitro effect of lipoxin A4 on airway epithelial cells was also examined. RESULTS: A significant concentration of lipoxin A4 was found in nasal secretions, and the concentration was increased in patients with allergic rhinitis. The mRNA expressions of 5-LOX, 15-LOX-1, FPRL-1, and CysLT1R were significantly greater in nasal polyps than in inferior turbinates. FPRL-1 was localized in nasal epithelial cells. Lipoxin A4 inhibited tumor necrosis factor alpha-induced interleukin 8 release from airway epithelial cells via its receptor FPRL-1. CONCLUSIONS: These results indicate that lipoxin A4 may play a role in the resolution of upper airway inflammation. A low concentration of lipoxin A4 may be involved in chronic inflammation of the upper airways.

Expression and localization of aquaporin 1, 2, 3, 4, and 5 in human nasal mucosa.

BACKGROUND: Aquaporins (AQPs) are water-specific membrane channel proteins that regulate water homeostasis for cells and organisms. The purpose of this study was to elucidate the role of AQPs 1, 2, 3, 4, and 5 in normal and diseased human nasal mucosa. METHODS: Nasal polyps were obtained from eight patients with chronic rhinosinusitis (CRS). Inferior turbinate tissue was obtained from five patients with allergic rhinitis (AR) and from six patients with septal deviation (controls). Expression of AQP1-5 mRNA was examined using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting, and tissue localization of AQP1-5 was studied by immunohistochemistry. Semiquantitative RT-PCR was used to investigate disease-specific changes in the expression in AQP1, -3, and -5 mRNA. RESULTS: Expression of AQP1, -3, -4, and -5 mRNA and AQP1-5 protein were confirmed in normal human nasal mucosa. Immunohistochemical studies revealed that AQP1 was localized in fibroblasts (especially in the subepithelial area) and endothelial cells of blood vessels, AQP2 was localized in the cytoplasm of epithelial cells and acinar cells, AQP3 was localized in the basolateral sites of epithelial cells and acinar cells, AQP4 was localized in the basolateral sites of acinar cells, and AQP5 was localized in the apical sites of epithelial cells and acinar cells. Semiquantitative RT-PCR revealed that there were no significant differences in the mRNA expression of AQP1, AQP3, and AQP5 among control, AR, and CRS patients. CONCLUSION: AQP1, -2, -3, -4, and -5 were present in normal human nasal mucosa. mRNA expression of AQP1, -3, and -5 did not change among control, AR, and CRS patients.

Role of platelet-derived growth factor in airway remodeling in rhinosinusitis.

BACKGROUND: The purpose of this study was to elucidate the role of platelet-derived growth factor (PDGF) in the pathogenesis of rhinosinusitis. METHODS: Nasal mucosa and polyps were obtained during surgery in patients with allergic rhinitis, chronic rhinosinusitis (CRS) without asthma, and CRS with asthma. PDGF concentrations in nasal discharge were measured, and the histological distribution and expression levels of mRNA for PDGF and PDGF receptors were examined. PDGF-producing cells were determined by double-staining for PDGF and CD68 or major basic protein. RESULTS: The concentration of PDGF was significantly higher in CRS with asthma. An immunohistochemical study showed that PDGF was localized in epithelial cells, gland cells, vascular endothelial cells, and inflammatory cells. Expression of PDGF increased in epithelial cells in all three diseases, in macrophages in CRS without asthma, and eosinophils in CRS with asthma, and PDGF receptors were detected in epithelial cells and submucosal fibroblasts. Increased expression of PDGF mRNA was found in CRS with asthma. CONCLUSION: The results indicate that PDGF is produced by macrophages, eosinophils, and epithelial cells in rhinosinusitis and that it acts on receptors in epithelial cells and fibroblasts. PGDF may be an important cytokine in the pathogenesis of rhinosinusitis by promoting tissue fibrosis and formation of nasal polyps.

Endoscopic ligation of the sphenopalatine artery and the maxillary artery for the treatment of intractable posterior epistaxis.

BACKGROUND: Intractable posterior epistaxis sometimes requires intensive treatment, such as surgery or embolization. Maxillary artery ligation has been widely used for the treatment of intractable posterior epistaxis. It is highly effective, but significant complications may occur, including an oroantral fistula and damage to the infraorbital nerve. Embolization is less invasive and can be performed in poor surgical candidates. However, it has more serious complications, such as facial nerve paralysis and hemiplegia. This investigation evaluates the effectiveness and complications of endoscopic ligation of the sphenopalatine or maxillary artery for the treatment of intractable posterior epistaxis. METHODS: Between April 2003 and March 2007, 46 patients were hospitalized for the treatment of severe posterior epistaxis in our University Hospital. Thirty patients were successfully treated by anterior and/or posterior nasal packing, and five patients were treated by electrocoagulation. Endoscopic ligation was performed under general anesthesia in 11 patients (6 men and 5 women; age range, 50-80 years). RESULTS: Eight patients underwent endoscopic ligation of the sphenopalatine artery, and three patients underwent endoscopic ligation of the maxillary artery through the middle meatus and posterior antral wall opening. There were no complications, and the patients' postoperative courses were uneventful. Recurrent epistaxis occurred in one patient on oral anticoagulants 15 months after ligation of the sphenopalatine artery, and it was successfully treated by anterior nasal packing. CONCLUSION: Endoscopic ligation of the sphenopalatine or maxillary artery is safer than arterial embolization and is less invasive than transantral ligation of the maxillary artery. This technique appears to be a simple and highly effective surgical treatment for patients with intractable posterior epistaxis.

[Clinical effectiveness of coblation-assisted inferior turbinoplasty].

BACKGROUND: Laser-assisted inferior turbinoplasty has become accepted as a common treatment for patients displaying allergic rhinitis with severe nasal obstruction. Coblation-assisted inferior turbinoplasty has recently been reported. The aim of this study was to evaluate the effectiveness of coblation-assisted inferior turbinoplasty, compared with laser surgery. METHODS: Between November 2004 and May 2007, a total of 29 patients were treated with coblation-assisted inferior turbinoplasty. We evaluated symptom scores at 1 month, 1 year and 2 years after surgery, compared with the results of Nd: YAG laser surgery. RESULTS: At 1 month after surgery, improvement rates of symptom scores were good and similar between coblation- and laser-assisted surgery. At 1 year after surgery, improvement rates of laser surgery had significantly decreased. However, improvement rates of coblation surgery had not changed at 1 and 2 years (sneeze, 64%; nasal discharge, 71%; nasal obstruction, 79%) after surgery. CONCLUSION: Coblation-assisted inferior turbinoplasty appears effective for the treatment of patients with allergic rhinitis and nasal obstruction.

[Endoscopic ligation of maxillary and sphenopalatine artery for intractable epistaxis].

We report the endoscopic ligation of the maxillary and sphenopalatine arteries for the treatment of intractable epistaxis. From March 2003 to February 2005, 17 patients (12 men, 5 women) with epistaxis were hospitalized in our department. Patient age ranged from 25 to 83 years, with an average age of 62 years. 8 patients were successfully treated using the conventional packing method, 2 patients were treated using electrocauterization, and 1 patient with macroglobulinemia was treated using plasma exchange therapy. 6 patients underwent endoscopic ligation of the maxillary and sphenopalatine arteries while under general anesthesia. The post operative courses were uneventful, and no recurrent bleeding has been noted. Endscopic ligation of the maxillary and sphenopalatine arteries is safer than intraarterial embolization and less invasive than conventional surgical approach for the ligation of maxillary artery. This technique appears to be a safe and effective surgical treatment for patients with intractable epistaxis.

[Image-guided endoscopic sinus surgery: a comparison of two navigation systems].

We evaluated the effectiveness of two navigation systems with optical tracking in endoscopic sinus surgery (ESS). The Signa SP/i Intraoperative navigation system (General Electric Co., Intraoperative NS) is advantageous in acquiring both real time and high-resolution images during surgery, compared to conventional image-guided navigation (Stealth Station TREON, Medtronic Inc., IGNS) that rely entirely on preoperative three-dimensional images. We studied the following in 14 patients treated with intraoperative NS and 19 treated with IGNS: 1) additional time for navigation system implementation, 2) available instrumentations in ESS, and 3) navigation system accuracy. Navigation systems required additional time to prepare ESS. The time lapse from admittance to the operating room to ESS onset was measured in patients under both systems and controls undergoing ESS without any image guidance. Preparation of the intraoperative NS required an additional 52 min and IGNS required 17 min compared to the control group. Based on operative instruments, the intraoperative NS has some limitations arising from the application of a high magnetic field. Surgical instruments must not be attracted by the magnetic field in the operating room. So those used in our study were thoroughly examined and some remanufactured using MR safe materials. All instruments in ESS could be used in surgical guidance during surgery in the IGNS. Anatomic landmarks were accurately visualized using intraoperative NS and IGNS. Intraoperative NS renews the image during surgery, so surgeons could confirm the surgical outcome during ESS. Since the average distant error in both systems was between 1 mm and 2.5 mm, we confirmed that accuracy obtained with both navigation system was suitable for ESS completion. The intraoperative NS renewed the image during navigation. In conclusion, both navigation systems are sufficient for accurate image navigation in ESS, but navigation systems must be selected based on the individual case.

[Endoscopic resection of benign and malignant tumors in the nasal cavity and paranasal sinus].

Endoscopic resection of nasal and paranasal sinus tumors is more aesthetic and less invasive than conventional resection, such as Luc's operation and lateral rhinotomy. We clarified the effect of radical endoscopic tumor excision and the control of local bleeding hazardous in endoscopic surgery. Subjects were patients with benign lesions in the nasal cavity, medial wall of the maxillary sinus, ethmoid sinus, and/or sphenoid sinus without concurrent malignant lesions. Although patients selection for malignant tumor excision was based on (1) possible en bloc resection, (2) low-grade malignant tumors, and (3) tumors in the nasal cavity and adjoining paranasal sinus, the final decision was made individual. Subjects were 23 patients with benign tumor (10 inverted papilloma, 9 hemangioma, 2 juvenile angiofibroma, and 2 other tumors) and 4 with malignant tumor (olfactory neuroblastoma, acinic cell carcinoma, squamous cell carcinoma, and chondroid chordoma) in the nasal and paranasal sinus. The tumor was resected en bloc except for patients with inverted papilloma (2 cases) and chondroid chordoma. Recurrence in benign tumors was zero during a mean observation of 21 months. One with chondroid chordoma, however, suffered a recurrent lesion 7 months after the initial operation. The lesion was successfully salvaged by a similar endoscopic procedure and subsequently treated with electron beam irradiation. Preoperative arterial embolization, laser coagulation, and ligation of the sphenopalatine artery were very useful in reducing blood loss during surgery and maintaining a clear endoscopic view. In intraoperative bleeding volume, less than 100 ml of bleeding occurred during surgery in 23 of 27 patients. The endoscopic excision of benign lesions in the nasal and paranasal sinus is thus as effective as conventional radical surgery. Endoscopic removal of malignant lesions remains controversial because of the small number of patients and short postoperative observation.

Malignant external otitis: treatment with prolonged usage of antibiotics and Burow's solution.

Malignant external otitis is a severe infection of the external auditory canal, generally caused by Pseudomonas aeruginosa in elderly diabetics patients. We describe a case of malignant external otitis in a 63-year-old man with severe otalgia, purulent otorrhea and polypoid granulation of the external auditory canal. Local debridement, insulin treatment and 6-week intravenous antibiotic therapy with carbapemens were very effective and the granulation tissue disappeared completely. However, the patient readmitted for recurrent disease 3 weeks later, despite the oral and ear drop administration with new quinolone. No recurrence has been noted after 4-week additional treatment with intravenous carbapenems followed by 3-week treatment with Burow's solution as ear drops.

[Epidemic study of pet allergy in Wakayama Prefecture].

In Japan, the number of households who have pets has gradually increased, together with the number of people who have pet allergies. Many reports exist on pollen and mite allergy, but few on pet allergy. We conducted an epidemic study in 531 first-year junior high school students in Wakayama prefecture in 1999. Questionnaires covered allergy and measurement of total IgE antibody using CAP system (Pharmacia Co. Ltd.) and specific IgE antibody using MAST26 system (Hitachi chemical Co. Ltd.). Of 306 students having pets, 11 were allergic to dogs, 11 to cats, 8 to both, and 1 to rabbits. Clinical symptoms were various. No differences in symptoms were observed among allergens. Serum total IgE tended to increase in students who suffered from pet allergies. Positive rates of specific IgE antibodies were high in mites and Japanese cedar pollen (36.7% for mites and 37.0% for Japanese cedar pollen), and also in dogs and cats (15.4% for dogs and 18.2% for cats). Specific dog and cat IgE antibodies increased significantly (p = 0.033 for dog and for p < 0.0001 cat), but no significant correlation was found between the positive specific IgE antibody and history of pet keeping.

[Combined MTX.5-FU.CDGP for the treatment of head and neck cancer].

Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP) with methotrexate (MTX) and leucovorin (LV) was administered for modulation in patients with head and neck cancer. We treated 19 patients with MTX.5-FU.CDGP consisting of 150 mg/body of MTX on day 1 followed by a 3-day continuous infusion of 5-FU at 3,500 mg/m2 and 17 injections of LV at 15 mg and infusion of CDGP at 100 mg/m2. Six patients had recurrent head and neck cancer, and 13 had newly diagnosed disease. Eleven of the new patients were concurrently treated with radiation therapy. Treatment-associated toxicity was significant, including mucositis and myelosuppression, but acceptable. Sixteen patients were eligible for evaluation of response. The overall complete response rate was 75.0% (12/16). Patients treated with radiotherapy had a 90.0% (9/10) overall complete response rate.

[2001 survey of pollen in Wakayama City with a real-time pollen counter].

Self-care is gradually being recognized as important in the treatment of pollinosis, based up to now on data on airborne pollen. To determine the real-time numbers of airborne pollen would be more useful in self-care, however, so we studied the usefulness of the real-time pollen counter. Between Feb. 2, 2001, and Apr. 26, 2001, 4 types of airborne pollen i.e., Japanese cedar, Japanese cypress, black alder, and beech observed in Wakayama City were counted with a Durham pollen counter and a real-time pollen counter (Yamato Manufacturing Co. Ltd.). Correlation between the 2 pollen counters was r = 0.69 for Japanese cedar in March and r = 0.89 for Japanese cypress in April. A high correlation was observed between outcomes of the 2 pollen counters. The amount of pollen from black alder and beech was less than that from Japanese cedar and cypress. Unexpected peaks were observed not related to the pollen number is apparently due to snow. We have taken measure against snow, so we concluded that the real-time pollen counter was useful in counting the amount of airborne pollen over time.

[Outcome of neonatal screening for hearing loss in neonatal intensive care unit and well-born nursery infants].

A newborn hearing screening was conducted on 319 neonatal intensive care unit (NICU) and 1200 well-born nursery (WBN) infants. Mean NICU birth weight was 1997 g and mean gestational age 34 weeks. Auditory brainstem response was studied in screening in NICU infants. Otoacoustic emission (OAE) or automated auditory brainstem response (AABR) was used in primary WBN screening. All infants not bilaterally passing hearing screening before discharge were recalled for outpatient retesting. If the outcome was still failure, ABR screening was conducted. The prevalence of infants diagnosed with hearing loss was 1.1% (16 of 1519). Of these 16, 75% were from the NICU and 75% were at risk for hearing loss. Mean age at hearing loss identification was 12.9 weeks in the WBN and mean age at hearing aid fitting was 16.1 weeks. Mean age at hearing aid fitting was lower for WBN than for NICU infants. Hearing loss identification and hearing aid fitting are thus feasible in NICU and WBN infants in universal newborn hearing screening.