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Purpose: To evaluate the robustness of the latest periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technology from each vendor against head movements and to investigate their characteristics for effective clinical use., Methods: Using a phantom simulating the T2-weighted image of the human brain, images were acquired with devices from CANON MEDICAL SYSTEMS (Tochigi, Japan; hereinafter "Canon"), GE HealthCare (Chicago, IL, USA; hereinafter "GE"), Philips (Amsterdam, Netherlands), and Siemens Healthineers (Forchheim, Germany; hereinafter "SIEMENS"). The head motion patterns were divided into rotation angle dependency (single rotation and multiple rotations) and rotation frequency dependency and evaluated using structural similarity (SSIM)., Results: For rotation angle dependency, Canon was robust against small rotation angles and fine movements. Despite the rotation angle, GE was robust against movements, with deep learning reconstruction (DLR) improving correction functionality. Philips could be used with compressed sensitivity encoding (CS), and robustness varied with blade width. SIEMENS was robust against large movements. For rotation frequency dependency, results were similar across the 4 vendors., Conclusion: The rotation angle and rotation frequency dependencies of the PROPELLER technology from the 4 vendors were quantitatively evaluated. Understanding the characteristics of PROPELLER allows for the possibility of providing diagnostic-quality images even for patients who move during head MRI exams by appropriately using PROPELLER.

Downhill varices are usually caused by superior vena cava (SVC) obstruction due to bronchogenic carcinoma or mediastinal tumors. These structures exhibit retrograde blood flow and are located in the proximal esophagus. Varices in the hypopharynx resulting from mediastinal thyroid tumor are extremely rare. A 70-year-old man with a 35-year history of a growing thyroid tumor on the right side of his neck visited a local hospital. Fine-needle aspiration cytology of the tumor revealed benign goiter. Contrast-enhanced computed tomography showed a huge tumor (13 × 10 × 5 cm) in the right to left lobe of the thyroid that extended into the mediastinum. A well-enhanced mass mimicking hypopharyngeal cancer was identified in the hypopharynx. Endoscopic examination showed varices in the postcricoid region, so biopsy was contraindicated. The preoperative diagnosis was adenomatous goiter and hypopharyngeal varices caused by obstruction of the internal jugular and brachiocephalic vein by the goiter. Total thyroidectomy was performed and the hypopharyngeal varices had disappeared by the next day. The histopathological diagnosis of the thyroid tumor was poorly differentiated carcinoma. Mediastinal thyroid tumor rarely causes downhill varices due to SVC obstruction. However, signs of SVC obstruction were absent in this case, and varices were present in the hypopharynx, not in the upper esophagus. Obstructed venous flow from the thyroid plexus might circulate via the superior laryngeal vein and cause varices in the postcricoid region. When a patient with a large mediastinal tumor has a tumor-like lesion in the hypopharynx, downhill varices should be considered before scheduling a biopsy.

Objective: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC., Materials and Methods: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available ( n  = 2) and for discrepant central pathological judgements ( n  = 6). The remaining 39 patients were processed for data analysis., Results: As pretreatment examinations, computed tomography (CT) was performed for the brain ( n  = 8), neck ( n  = 39), and chest ( n  = 32), magnetic resonance imaging (MRI) for the brain ( n  = 4) and neck ( n  = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity ( n  = 1), nasal cavity/paranasal sinuses ( n  = 16), nasopharynx ( n  = 2), oropharynx ( n  = 4), hypopharynx ( n  = 2), larynx ( n  = 6), salivary gland ( n  = 3), thyroid ( n  = 2), and others ( n  = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group ( n  = 27), non-CRT group ( n  = 8), and best supportive care group ( n  = 4). The CRT group included concurrent CRT (CCRT) ( n  = 17), chemotherapy (Chemo) followed by radiotherapy (RT) ( n  = 5), and surgery (Surg) followed by CCRT ( n  = 5). The non-CRT group included Surg followed by RT ( n  = 2), Surg followed by Chemo ( n  = 1), RT alone ( n  = 2), and Chemo alone ( n  = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group ( n  = 22) and the Chemo without concurrent RT group ( n  = 9)., Conclusion: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Matsuyama, Ueki, Okamoto, Nagao, Honda, Yamazaki, Okabe, Togashi, Shodo, Ota, Takahashi, Omata, Yokoyama, Saijo, Tanaka, Tsukahara, Kitahara, Uemura, Yoshimoto, Matsumoto, Okami, Sakai, Takano, Kondo, Inohara, Eguchi, Oridate, Tanabe, Nakamizo, Yokoshima, Miura, Kitani and Horii.)

Background: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date., Methods: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality., Results: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m 2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m 2 ; 17 patients)., Conclusions: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m 2 ., (© 2020 American Cancer Society.)

One triterpene and five triterpene glycosides, including four new compounds, have been identified in the underground parts of Glycyrrhiza bucharica, which was shown to be closely related to Glycyrrhizin-producing Glycyrrhiza species, G. uralensis, G. glabra and G. inflata, based on their chloroplast rbcL sequences. Two known compounds were identified squasapogenol and macedonoside C. The structures of four new compounds, bucharosides A, B, C, and D, were determined to be 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucuronopyranosyl-(1→2)-β-D-glucuronopyranosyl-22-O-α-L-rhamnopyranosyl squasapogenol, 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucuronopyranosyl-(1→2)-β-D-glucuronopyranosyl-macedonic acid, 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucuronopyranosyl-(1→2)-β-D-glucuronopyranosyl-squasapogenol, and 22-O-α-L-rhamnopyranosyl squasapogenol, respectively. Contents of these triterpene glycosides were less than 0.5% of dry weight, and no main saponin, like glycyrrhizin or macedonoside C found in other Glycyrrhiza species, was found in the underground parts of G. bucharica.

Phlegmonous gastritis is a rapidly progressive bacterial infection of the stomach wall. It has a high mortality rate and aggressive treatment, either with antibiotics or surgical resection, is required. Here, we report an extremely rare case of phlegmonous gastritis associated with advanced esophageal cancer. A 65-year-old Japanese man was urgently admitted to the hospital due to pyrexia and gastrointestinal symptoms. Abdominal computed tomography revealed widespread diffuse thickening of the gastric wall. On endoscopic examination, an ulcerative mass was detected at the lower thoracic esophagus, and a markedly elevated submucosal lesion was present in the middle of the stomach body. Biopsy specimens taken endoscopically from the esophageal tumor confirmed a diagnosis of squamous cell carcinoma. Gastric biopsy cultures were positive for Streptococcus viridans, leading to a diagnosis of phlegmonous gastritis associated with esophageal cancer. After the patient's condition improved with preoperative antibiotic administration, we performed a thoracoscopic esophagectomy, a total gastrectomy and a reconstruction of the gastrointestinal tract using a pedicled right colon. Histological examination of the resected specimen confirmed that the gastric mass was compatible with a phlegmon.

Background: Patients with head and neck or esophageal cancer who undergo resection and reconstructive surgery sometimes develop fistulae that exhibit delayed wound healing. We developed a novel negative pressure wound therapy (NPWT) that employs a Penrose drain. This case series report describes its effect on the wound healing and treatment duration of cancer patients with postoperative fistulae., Methods: This consecutive case series consisted of all patients from February 2014 to February 2017 who underwent resection and reconstruction for head and neck or esophageal cancer and who then developed a fistula that was treated with either NPWT or a second flap that did not resolve the fistula or led to fistula recurrence and was then treated with NPWT. A Penrose drainage tube was inserted into the fistula, and a NPWT device was applied., Results: Eleven patients (10 males, 1 female; mean age, 67.4 years) underwent NPWT for fistulae that arose after tumor resection and reconstruction (n = 6) or after fistula reconstruction (n = 5). The resection was for esophageal (n = 4), laryngeal (n = 3), oral (n = 2), and hypopharyngeal (n = 2) cancer. In 9 cases, 1 week of NPWT led to rapid and complete wound healing. In 2 cases, complete healing occurred after 3-4 weeks of NPWT., Conclusions: Our NPWT applies continuous negative pressure inside the fistula only and dramatically promoted fistula healing. This approach may work by cleaning the fistula and promoting mucosal surface adhesion. It is particularly effective when the tissue surrounding the fistula is soft due to fresh tissue transfer.

Carcinosarcoma (CS) is a rare tumor, consisting of both carcinomatous and sarcomatous components. In this paper, we present a case of CS arising from a pleomorphic adenoma (PA) of the submandibular gland. A 64-year-old Japanese man presented with a left submandibular mass that had developed for 20 years with complaints of pain for the last 3 months. Magnetic resonance imaging showed a lesion involving the left submandibular gland. The patient underwent total dissection of the left submandibular gland and left cervical lymph nodes. Upon gross examination, the mass appeared completely covered by fibroadipose tissue measuring 46×42×45 mm; sectioning revealed a solid-white nodule with central bleeding and necrosis, invading into the surrounding adipose tissue. Microscopically, the presence of carcinomatous and sarcomatous components in the fibro-myxomatous stroma was detected, suggestive of pre-existing PA. The carcinoma component was diagnostic of salivary adenocarcinoma, not otherwise specified, whereas the sarcomatous component exhibited features of osteosarcoma characterized by formation of osteoid. As the border between the carcinomatous and sarcomatous components was not evident, CS may have occurred via transformation of the carcinoma into sarcoma. Tumor metastasis was detected in the cervical lymph nodes. Immunohistochemically, AE1/AE3 expression was noted in the carcinomatous component, but not in the osteosarcoma component. Both components were diffusely positive for vimentin. Four months after the operation, the patient developed a metastatic CS lesion in the lung, suggesting tumor aggression.

The elderly population has been increasing, in Japan. With this increase, the incidence of elderly patients with head and neck cancer is likely to increase concomitantly. Therefore, a strategy for addressing this problem must be defined. In this study, a questionnaire for head and neck cancer specialists, certified by the Japanese Society of Head and Neck Surgery, is analyzed. The survey was conducted in 225 head and neck cancer specialists, and 122 answers were complete and bare analyzed in this study. Comorbidity was found to be the most important factor in decision making for head and neck cancer, even though it is subclinical. Especially important was the cognitive state, the dysfunction of which might decrease the feeling of struggle against the disease. These results indicate that we must choose the appropriate treatment based on the evaluation of the physical and emotional condition of the patients and their families, not only on their age. However, this suggestion includes some problems, such as the fact that the criteria are not definite and the choice of the treatment might be at risk of being judged by only one doctor.

Background: Successful vascular anastomosis is essential for the survival of transferred free tissue. Arterial anastomosis is typically uncomplicated because the lumen is easily maintained and the vessel walls have elasticity. Venous anastomosis, however, is more time consuming because the vessel walls are thin and extensible. This article describes, reviews, and compares 3 currently used venous anastomosis techniques., Methods: From April 2012 through January 2014, free tissue transfer and supercharging pedicled tissue transfer were performed in 107 and 10 patients, respectively, at our hospital. According to the anastomotic technique used, patients (83 men and 34 women; mean age, 60.6 years) were divided into interrupted suture, continuous suture, and microvascular anastomotic coupling device (MACD) groups. Medical records were reviewed, and postoperative results were analyzed., Results: The diameter of anastomosed veins did not differ significantly among the groups. However, among the interrupted suture, continuous suture, and MACD groups, there were significant differences in vascular anastomosis time (51, 43.9, and 29.5 minutes, respectively) and transferred tissue ischemic time (151.9, 139.1, and 117.5 minutes, respectively). Surgical site infection occurred in 9 patients, and flap necrosis occurred in 2 patients. However, complication rates did not differ significantly among the 3 groups., Conclusions: The venous anastomosis technique does not affect the complication rate but does affect anastomosis time and flap ischemia time. On the basis of these results, we believe that the continuous suture and MACD techniques are easier and safer for venous anastomosis than is the traditional interrupted suture technique.

Background: Descending necrotizing mediastinitis (DNM), a severe infection with a high fatality rate, develops in mediastinal spaces due mainly to deep cervical abscesses. The majority of causative microbes of DNM are Streptococci and oral anaerobes. DNM associated with Lactobacillus-infection is rather rare., Case Presentation: A 69-year-old male with an unremarkable past medical history was referred to our hospital for surgical resection of advanced laryngeal cancer. Full examination revealed a neck abscess and DNM with a background of untreated diabetes mellitus. Initially, he was treated with meropenem. However, Lactobacillus plantarum was isolated from surgical drainage of a mediastinal abscess. Despite using antibiotics capable of eradicating all isolates with susceptibilities not differing significantly from those of the neck and mediastinal abscesses, we attributed DNM to the L. plantarum detected only in the mediastinal abscess. After DNM treatment, he underwent total pharyngolaryngectomy with bilateral neck dissection followed by reconstruction using free jejunum. He was discharged fully recovered., Conclusion: We concluded that L. plantarum as the sole cause of the mediastinal abscess in the present case cannot be ruled out. As the number of immunocompromised patients increases, we should be cautious regarding this "familiar" microbe.

We describe 3 cases of metachronous hypopharyngeal cancer developing after laryngeal cancer had been treated with both radiotherapy and total laryngectomy. All 3 patients were men, 2 were 89 years old, and 1 was 65 years old. All patients had undergone total laryngectomy and radiotherapy for cancer for the glottis more than 20 years earlier. All patients underwent total hypopharyngectomy with jejunal free flap reconstruction. Surgery was complicated by scars from previous cancer treatment, and highly sophisticated surgical skills are needed, especially for preparing the recipient vessels. The postoperative period was largely uneventful and without fatal complications, however, 2 of the 3 patients died of distant metastasis 22 months and 31 months after surgery.

Neoplasm of follicular dendritic cells (FDC), follicular dendritic cell sarcoma (FDCS), is a rare tumor of intermediate to high-grade malignancy in lymph nodes and visceral organs. Reported herein is a case of FDCS arising from cervical lymph nodes in a 16-year-old Japanese boy, who died of the disease 3 years after diagnosis. The tumor cells were pale eosinophilic and elongated with euchromatic nuclei and were positive for CD21, clusterin, and CNA-42 on immunohistochemistry, as well as desmosome-like junctions on electron microscopy. The presence of microtubuloreticular structures (MTRS) in the tumor cells and associated lymphocytes characterized this case, suggesting some viral infection, although qualitative polymerase chain reaction of genomic and complementary DNA obtained from the tumor failed to demonstrate any viral infection at the laboratory level. The stimulation of dispersed tumor cells and peripheral blood mononuclear cells with mAb to CD3 and interleukin-2 was attempted; and the cell line established by the authors (FDCS-Sa) was stimulated with iododeoxyuridine. Virus-like particles (VLP) were successfully induced from each cellular source. The VLP, 100 nm in diameter, showed an electron-dense thorny envelope and granular core. This is the first case of FDCS with MTRS accompanying VLP production in vitro.

Electrochemical impedance spectroscopy was conducted on a series of hydrous ruthenium oxides, RuO(2).xH(2)O, (x = 0.5, 0.3, 0) and a layered ruthenic acid hydrate (H(0.2)RuO(2.1).nH(2)O) in order to evaluate their protonic and electronic conduction. The capacitor response frequency was observed at lower frequency for RuO(2).xH(2)O with higher water content, which was suggested to be due to electrolyte exhaustion within the film and/or utilization of hydrated interparticle micropores that have high ionic resistance. Analysis of the impedance data indicated that the charge-transfer resistance through the film is not significantly affected by the water content in RuO(2).xH(2)O, and the capacitor frequency response is dominated by the protonic conduction. The capacitor response frequency of layered H(0.2)RuO(2.1).nH(2)O was comparable to RuO(2).0.5H(2)O. The high specific capacitance at low frequency for layered H(0.2)RuO(2.1).nH(2)O is attributed to the utilization of the expandable hydrous interlayer, which accounts for the ionic conduction. The present results demonstrate the importance of hydrous regions (either interparticle or interlayer) to allow appreciable protonic conduction for high energy and high power electrochemical capacitors.

Objective: Sensory disturbance due to excision of the great auricular nerve in patients who have undergone parotidectomy sometimes causes discomfort to the patients. In order to reduce the postoperative discomfort of the pinna, we tried to preserve the posterior branch of the great auricular nerve., Methods: Forty patients with parotid tumor were included in this study. Twenty-one of these patients had pleomorphic adenoma, 16 had adenolymphoma and 3 had a low grade malignant tumor. Sensations of the pinna and the quality of life (QOL) after parotidectomy were evaluated using a 0-100 Visual Analogue Scale (VAS) assessed at 2 weeks, 1 month, 2 months, 3 months and 6 months after parotidectomy., Results: The posterior branch of the great auricular nerve was preserved in 26 out of 40 patients (65%). No difference was observed in the incidence of complications except sensory disturbance of the pinna with this surgical procedure as compared to the surgical technique where the great auricular nerve was excised. The VAS score for the sensation was significantly higher in the group of patients whose great auricular nerve was preserved at 2 months (35.0+/-20.8 vs. 18.5+/-9.2), 3 months (64.4+/-18.3 vs. 26.4+/-13.8) and 6 months (66.9+/-16.2 vs. 26.6+/-11.4) after parotidectomy. The VAS score for the QOL was also significantly higher in the group of patients whose great auricular nerve was preserved at 2 months (50.3+/-21.8 vs. 35.1+/-14.5), 3 months (69.5+/-27.5 vs. 45.9+/-22.6) as well as 6 months (71.9+/-24.1 vs. 45.7+/-19.1) after parotidectomy., Conclusion: Preservation of the posterior branch of the great auricular nerve during parotidectomy is valuable in order to reduce the postoperative sensory disturbance of the pinna that follows conventional surgery. It further helps to improve the QOL of these patients after parotidectomy.

Objective: In order to clarify the factors affecting the survival of flaps, we performed a retrospective study on free flaps (187) used for reconstruction in head and neck surgery in 182 patients., Methods: Free jejunum flaps were used on 68 occasions, rectus abdominus myocutaneous flaps on 67, radial forearm flaps on 49, scapular osteocutaneous flaps on 2 and latissimus dorsi myocutaneous flap on ones occasion, during the period from May 1996 to April 2003. Post-operative circulatory complications at the recipient site were analyzed mainly in relation to a history of previous surgery, radiotherapy and chemotherapy., Results: Circulatory crisis was observed in seven cases and circulation was restored in two of them after emergency exploration, whereas the other five flaps failed to survive. The overall failure rate of free flaps was 2.7%. Wound infection at the recipient site was frequent in patients with a history of previous local cervical surgery. Flap failure was significantly more frequent in patients with a history of previous surgery and infection, except for 2 patients in whose case the microsurgical technique was inadequate. Flap failure was not observed in those patients whose irradiation field could be analyzed, or in the patients who received chemotherapy. Although the incidence of circulatory crisis as a consequence of inadequate microsurgical technique was observed in the early period of this retrospective study, their frequency has diminished in the last 2 years., Conclusion: The survival of flaps was affected by a history of previous surgery following wound infection, although a history of irradiation and chemotherapy would have no effects on flap failure. The appropriate choice of vessels and surgical skill are crucial for the success of free flaps from our experience. Emergency exploration was also crucial for the survival of the flap in the case of circulatory crisis.

This is the first case report of malignant fibrous histiocytoma of the hypopharynx in a young adult with preservation of the larynx. Although the initial histopathological diagnosis of the biopsy was benign fibrous histiocytoma, subsequent histopathological evaluation of the surgical specimen was malignant fibrous histiocytoma. Thereafter, re-excision of the histiocytoma with a wide margin was performed coupled with reconstruction of the hypopharynx while preserving the larynx. We also report the good long-term survival of this case of low-grade type of malignant fibrous histiocytoma.

We reviewed 79 patients with squamous cell carcinoma of the lateral wall of the oropharynx who received treatment at the Cancer Institute Hospital. Tokyo, between 1971 and 1990. There were 67 men and 12 women, aged 31 to 81 years (average 59.2 years). The tumors could be staged by TNM classification (UICC 1987) as follows: Stage 10 Stage II 12, Stage III 27, Stage IV 40. It must be noted that more than 50% of the tumors were classified as stage IV. As the initial treatment, 50 patients underwent radical radiotherapy, and the remaining 29 were treated mainly by surgery after pre-operative radiation. Some patients underwent adjuvant chemotherapy, but the role of chemotherapy was not considered in this study. The purpose of the present study was to determine the prognostic factors and to determine the survival rate after each treatment modality. The results were as follows: i) Patients with either T4, over N2b or a stage IV tumor had a significantly poor prognosis. ii) Cox multivariate analysis revealed that age, local extension (base of tongue, anterior pillar, soft palate and mid-line), pathological findings (poorly, moderately or well differentiated), tumor type (exophytic or endophytic) were not useful prognostic factors. iii) Radiosensitivity was not reflected in the survival rate judging from the high recurrence rate (44%) after radical radiotherapy. On the other hand, local recurrence after radical resection was seen in 18% of the patients. iv) Analysis of the data supported the recommendation of surgery after preoperative radiation as the treatment for stage III patients. It seems difficult to find the best treatment modality for stage IV patients in order to improve the survival rate, and this is an issue that still remains to be resolved. v) From the study of the surgical specimens, we are unable to demonstrate a significant survival advantage of the patients with a high grade radiation effect, or patients with no vessel involvement.

Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reaction, However, the mechanism of accumulation of these cells has not yet been well clarified. We hypothesized that cytokines generated from the nasal epithelial cells contributed to the accumulation of these cells in the nasal epithelial layer. Recently tumor necrosis factor (TNF) was shown to promote polymorphonuclear neutrophils and eosinophils migration. And also TNF increased eosinophil binding to vascular endothelial cells. In this in vitro study we examined whether or not nasal epithelial cells can produce TNF-alpha and also whether or not glucocorticosteroid fluticasone propionate (FP) can modulate TNF-alpha production from nasal epithelial cells. Nasal epithelial cells constitutively produce TNF-alpha in accordance with the nasal epithelial cells' number and this was substantially increased in the state of nasal epithelial cell's proliferating. FP significantly reduced the level of TNF-alpha in the supernatant of cultured nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days caused significant reduction of TNF-alpha level in the supernatant of cultured nasal epithelial cells during a further period of 6 days without FP. These data support the concept that structural cells play an active role in the control of allergic and related inflammatory processes.

We previously found that an increased number of mucosal mast cells accumulated in the tumor site of nasal inverted papilloma as well as in the epithelial layer of the allergic nasal mucosa. However, the mechanism of accumulation of mucosal mast cells has not yet been clarified. The purpose of this study was to evaluate the cytokines produced by inverted papilloma cells, which would be important for the accumulation of mucosal mast cells. We found that the supernatant of the monolayer of cultured inverted papilloma cells contained GM-CSF, IL-6 and IL-8. IL-2, IL-3, IL-4 and IL-5 were not detected. Contrary to the quantities of cytokines detected in the supernatant of cultured allergic nasal epithelial cells, the quantities of IL-6 and IL-8 were greater in the supernatant of cultured inverted papilloma, whereas that of GM-CSF was less. Immunohistochemical study revealed the distribution of cytokines: GM-CSF was detected near the basement membrane of the tumor site, while IL-6 and IL-8 were detected in the superficial layer of nasal inverted papilloma. Interestingly, the tumor site near the basement membrane is also the site of accumulation of mucosal mast cells, suggesting that GM-CSF produced by nasal inverted papilloma cells may be one of the most important factors in the accumulation of mucosal mast cells.

We previously found that an increased number of mast cells and eosinophils accumulated in nasal inverted papilloma and in the nasal mucosa of allergic subjects. Two subtypes of mast cells, i.e., mucosal mast cells and connective tissue mast cells are known to be present in the allergic nasal mucosa. Eosinophils in the allergic nasal mucosa are also heterogeneous. In addition, we demonstrated accumulation of formalin-sensitive mast cells at the tumor site of nasal inverted papilloma. The morphological characteristics and function of mast cells and eosinophils, however, have not yet been identified. The purpose of this study was to determine the ultrastructural characteristics of mast cells and eosinophils in relation to their function in tumor tissue. The results revealed two subtypes of mast cells in nasal inverted papilloma, one distributed mainly in the tumor site, the other mainly in the stromal site. These two subtypes of mast cells had different ultrastructural characteristics. In contrast to stromal mast cells, mast cells in the tumor site were characterized by a smaller cell diameter, fewer specific granules and a higher rate of degranulation. This suggested that they may have played some role in the pathogenesis of the tumor, however, their precise function is still unknown. In comparison with the mast cells in the allergic nasal mucosa, previously reported by Okuda et al, the mast cells in the tumor site were similar to those in the epithelial layer of the allergic nasal mucosa (MMCs), while mast cells in the stromal site resembled those in the lamina propria (CTMCs). There were no marked morphological differences between eosinophils in the tumor site and the stromal site.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to clarify the existence and the role of endothelin in the respiratory tract, we investigated the distribution of endothelin in the respiratory mucosa by immunohistochemistry. The endothelin release from cultured nasal epithelial cells of allergic mucosa and polyp mucosa was also studied by RIA. Endothelin was distributed in the epithelium, endothelium of vessels, and submucosal glands in both nasal and bronchial mucosa. Moreover, in bronchial mucosa smooth muscles of bronchus had also positive staining of endothelin. On the other hand, 1.8 x 10(-11) pg of endothelin was released to culture medium from single cultured epithelial cell of allergic nasal mucosa, and 2.8 x 10(-11) pg of endothelin was released to culture medium from that of nasal polyp. These increase of endothelin was correlated with an increase of cultured epithelial cells from both nasal allergy mucosa and nasal polyp, of which the cell number was increased depend on the concentration of FCS. These results indicate that endothelin in the respiratory mucosa acts on not only control of blood flow and air flow, but also has some reaction which was related on the mucosal epithelium such as epithelial cilially movement. Endothelin has some role in inflammation because endothelin was increased more in nasal polyp culture medium than in allergic mucosa culture medium.

An increased number of mast cells and eosinophils can be recognized in the epithelial layer of nasal mucosa from allergic subjects; these cells are known to play an important role in the manifestation of nasal allergy. Eosinophils accumulate under the effect of eosinophil chemotactic factor released by mast cells. However, the mechanism of accumulation of mast cells has not yet been clarified. Our previous studies have shown that colony stimulating activity of the basophil/eosinophil lineage is enhanced under proliferative conditions for nasal epithelial cells. We therefore studied the distribution of mast cells and eosinophils in inverted papilloma of the nose, in which we can identify proliferation of nasal epithelial cells. Nasal inverted papilloma from 5 patients were examined for mast cell and eosinophil distributions. Serial staining of nasal inverted papilloma showed that the number of mast cells and the percentage of formalin sensitive mast cells within 50 microns of the tumor site and 50 microns above the basement membrane were 16576 +/- 5729/mm3 (90.8%) and 4697 +/- 304/mm3 (76.1%), respectively. However, in comparison with the tumor site, significant differences in the distribution and number of mast cells were seen in the stromal area. The number of mast cells and the percentage of formalin sensitive mast cells within 50 microns and 50 microns above the basement membrane were 2880 +/- 238/mm3 (0%) and 3096 +/- 152/mm3 (0%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to examine fluticasone propionate's mechanism of inhibiting nasal allergic symptoms, topical dosing of FP to patients with Japanese cedar pollinosis was started before the pollen scattering season, and the kinetics of basophilic cells and eosinophils which infiltrated into the surface of nasal mucous membrane were observed. Patients with Japanese cedar pollinosis were divided into two groups. Before and in the early period of the pollen scattering season, one group received FP and the other group a placebo, topically into the nostrils. In the mid and late season, both groups were treated with FP topical dosing. The study was carried out in the double blind manner. In the pre-, early and late season, specimens were scraped from the nasal mucosal surface, basophilic cell and eosinophil counts in the specimens were measured, and histamine and ECP contents in the specimens were also determined. Topical use of FP starting pre-season significantly inhibited symptoms of Japanese cedar pollinosis, as well as accumulation of basophilic cells and eosinophils in the nasal mucosal surface. Histamine and ECP contents in the nasal specimens tended to decrease with the topical use of FP.

An increased number of histochemically distinct mast cells and eosinophils can be observed in the tumor mass of nasal inverted papilloma. In order to elucidate the mechanism of this accumulation of mast cells and eosinophils in a local site, we examined the activity of conditioned medium (CM) in inducing differentiation and proliferation of basophilic cells and eosinophils from hematopoietic progenitors of peripheral blood mononuclear cells of the patients with allergic diseases. CM was obtained by the culture of nasal inverted papilloma cells (NIPC) and its activity was measured by determining colony proliferation in methylcellulose assay for 14 days. In the 14 day methylcellulose assay, the number of Eo-type colonies in the presence of 1, 5, 10 and 20% CM was significantly higher than the baseline number of Eo-type colonies (0%). Cytochemical analysis confirmed that the number of colonies of cells with metachromatic granules and histamine positive colonies in Eo-type colonies in the presence of 5, 10 and 20% NIPC-CM was significantly higher than that in the control. The number of ECP positive colonies in Eo-type colonies in the presence of 5% and 10% CM was also significantly higher than in the presence of 0.5% CM. Furthermore both histamine and ECP positive colonies were observed in Eo-type colonies. These results are consistent with the hypothesis that basophilic cells and eosinophils accumulate at nasal inverted papilloma sites at least in part by the recruitment of progenitors from the circulation and subsequent differentiation in situ in response to cytokines. Eosinophils and basophilic cells also commonly originate from committed granulocyte progenitors.

A simplified and accurate method for determination of naturally occurring vitamin D3 in bovine milk was established by high-performance liquid chromatography (HPLC) using successively reversed-phase and straight-phase columns. Exactly 25.0 ml of a sample of bovine milk was taken and the lipid was extracted with a solvent mixture of petroleum ether and ethyl ether (1:1) with small amounts of ethanol and Triton X-100, present. The extracted lipid was subjected to the first preparative HPLC using a Nucleosil 5C18 column (reversed-phase type) with acetonitrile-methanol (1:1) as the mobile phase, and a fraction containing vitamin D3 was isolated. The fraction was subsequently subjected to the second analytical HPLC using a Zorbax SIL column (straight-phase type) with 0.4% isopropanol in n-hexane as the mobile phase. Vitamin D3 was assayed by estimating the peak height on the chromatogram. The overall recovery and CV values were 92.1 +/- 8.7% and 9.4%, respectively, which were satisfactory. The proposed method was applied to several kinds of colostrum, early and later bovine milk in pairs. The assayed values in the colostrum of the group with large amounts of vitamin D3 administered before delivery to prevent parturient paresis were higher than those in the group with no administration. However, the values of the former group generally decreased in the respective early and later milk in step and there were few differences among those in the later milk of the two groups. The assayed values in later milk were 30-80 IU/liter.