Adenocarcinomas of the nasal cavity and paranasal sinuses: a clinicopathological and immunohistochemical study of 14 cases

Aims : To evaluate the clinicopathological profile of 14 cases of nasal and paranasal sinusal adenocarcinoma, and to assess the usefulness of immunohistochemistry in the differential diagnosis of primary and metastatic intestinal-type adenocarcinoma.
Methods and results : Fourteen cases of nasal and paranasal adenocarcinoma, treated at IPOFG, Lisbon, between 1976 and 2002, were studied. Clinical records were reviewed and expression of cytokeratin (CK)7 and CK20 and of neuroendocrine markers was evaluated. The male : female ratio was 3 : 1, and the mean age of the patients was 65.3 years. Ten cases occurred in the paranasal sinuses. There was a history of professional exposure to dust in three patients. Twelve cases were high-grade intestinal type adenocarcinomas (ITAC) and two were low-grade. CK7 was present in 2/9 ITAC cases and CK20 in 8/9 ITAC and in cases of mixed and mucinous histology. All high-grade cases showed neuroendocrine differentiation. Seven of the 12 patients with high-grade adenocarcinoma died of the disease, with a mean follow-up of 47.4 months.
Conclusions : Nasal and paranasal adenocarcinoma mostly occurs in men in the 7th decade. ITAC is the most frequent histological type. The pattern of CK7/CK20 was not useful in the distinction between primary and metastatic intestinal adenocarcinoma. However, in the former, neuroendocrine differentiation proved to be a valuable tool in that distinction.     

In vitro diagnosis of chronic nasal inflammation

BACKGROUND: Differential diagnosis of chronic nasal inflammation is insufficient when based solely on clinical examination and radiography of paranasal sinuses. Patients complain about more or less similar symptoms. Activation of mast cells and eosinophils is pivotal in nasal inflammation. OBJECTIVE: To compare tryptase and eosinophilic cationic protein (ECP) in nasal secretions in different forms of chronic nasal inflammation and to establish norm values. METHODS: The study included 1710 patients presenting with nasal complaints. Nasal secretions were gained by the cotton wool method and analysed for tryptase, as a marker of mast cell activation, and for ECP, as a marker of tissue eosinophilia and activation. Patients were grouped according to their diagnosis: chronic, non-allergic rhinosinusitis (sinusitis, n=194), non-allergic nasal polyposis (polyposis, n=138), non-allergic rhinitis with eosinophilia syndrome (NARES, n=198), isolated perennial allergic rhinitis (AR) (n=126), isolated seasonal AR (n=132), and patients allergic to both, seasonal and perennial allergens (n=193). Seven hundred and twenty-nine patients with nasal complaints due to a deviated septum and without any nasal inflammation served as controls. RESULTS: Nasal tryptase was highly significantly (P<0.001) elevated in polyposis, NARES, and in AR. ECP was highly significantly (P<0.001) elevated in all groups of patients suffering from chronic nasal inflammation. Based on our data and method we established norm values (95% confidence interval of mean value) for nasal tryptase in healthy adults, ranging from 12.0 to 18.7 ng/mL and for ECP ranging from 84.4 to 102.6 ng/mL. CONCLUSION: Mast cells and eosinophils are involved in non-allergic and allergic forms of chronic nasal inflammation. We established an in vitro assay for tryptase and ECP in nasal secretions and defined norm values based on our data and method. In vitro measurement of biological markers in nasal secretions provides important information for differential diagnosis and therapeutic strategies of chronic nasal inflammation.     

Effects on inflammation parameters of a double-blind,placebo controlled one-year course of SLIT in children monosensitized to mites

BACKGROUND: Clinical documentation about effects on local markers of inflammation of sublingual immunotherapy (SLIT) in children is still poor. METHODS: Twenty-four children (age range 4-16 years, average 8.5 years) monosensitized to house dust mites (HDMs) were randomized to receive active or placebo SLIT for this allergen according to a double-blind, placebo-controlled design. Before treatment and 10-12 months later the following parameters were checked: ECP and tryptase in sputum and nasal secretion, serum and nasal mite-specific IgE (sIgE), allergen-specific nasal challenge test (sNCT), nasal symptoms and tryptase after sNCT. RESULTS: Nasal tryptase and nasal IgE in basal conditions were unchanged in treated children but significantly increased in untreated children (P = 0.0156 and P = 0.0313, respectively). The threshold for sNCT was unchanged in both groups of children, but the symptom score after sNCT was unchanged in the placebo group and significantly decreased in the active group (P = 0.0084). The nasal tryptase after sNCT was unchanged in the active group and significantly increased in the placebo group (P = 0.0218). Intergroup comparison showed a significant difference in oral tryptase and nasal tryptase after sNCT in favour of the active group. CONCLUSIONS: These interim results after only 1 year of treatment show that SLIT in children monosensitized to HDMs is able to avoid the spontaneous increase in both nasal sIgE antibodies and in local allergic inflammation in basal conditions. These outcomes are confirmed and supported by the decrease of symptoms in the active group combined with the increase of nasal tryptase only in the control group in both cases after sNCT.     

Intranasal and inhaled fluticasone propionate for pollen-induced rhinitis and asthma

BACKGROUND: Studies suggest that nasal treatment might influence lower airway symptoms and function in patients with comorbid rhinitis and asthma. We investigated the effect of intranasal, inhaled corticosteroid or the combination of both in patients with both pollen-induced rhinitis and asthma. METHODS: A total of 262 patients were randomized to 6 weeks' treatment with intranasal fluticasone propionate (INFP) 200 microg o.d., inhaled fluticasone propionate (IHFP) 250 microg b.i.d., their combination, or intranasal or inhaled placebo, in a multicentre, double-blind, parallel-group study. Treatment was started 2 weeks prior to the pollen season and patients recorded their nasal and bronchial symptoms twice daily. Before and after 4 and 6 weeks' treatment, the patients were assessed for lung function, methacholine responsiveness, and induced sputum cell counts. RESULTS: Intranasal fluticasone propionate significantly increased the percentages of patients reporting no nasal blockage, sneezing, or rhinorrhoea during the pollen season, compared with IHFP or intranasal or inhaled placebo. In contrast, only IHFP significantly improved morning peak-flow, forced expiratory volume in 1 second (FEV1) and methacholine PD20, and the seasonal increase in the sputum eosinophils and methacholine responsiveness. CONCLUSIONS: In patients with pollen-induced rhinitis and asthma, the combination of intranasal and IHFP is needed to control the seasonal increase in nasal and asthmatic symptoms.     

经鼻内窥镜选择性鼻中隔粘膜下切除术

目的：探讨经鼻内窥镜选择性鼻中隔粘膜下切除术的意义及手术方法。方法：根据不同的手术目的对204例需要行鼻中隔手术的病人，经鼻内窥镜实施选择性鼻中隔粘膜下切除术。结果：采用该技术对单纯性鼻中隔偏曲患者手术临床治愈率100％，其手术有效治愈头痛、鼻阻及鼻出血等鼻中隔偏曲临床症状，达到临床治疗目的。未出现鼻腔粘连、鼻中隔穿孔等并发症。有2例形成鼻中隔血肿，经放置引流管处理后治愈。对于解除高位鼻中隔偏曲解剖异常引发的鼻窦炎，手术后效果良好。取鼻中隔软骨做为修补材料手术效果满意。结论：经鼻内镜选择性鼻中隔粘膜下切除术目的性强、方法灵活、创伤小、并发症少、手术效果确切。     

Eosinophil cationic protein and myeloperoxidase in nasal secretion as markers of inflammation in allergic rhinitis

The inflammatory component of allergic rhinitis was studied by measuring the concentration and content of eosinophil cationic protein (ECP, specific for eosinophils) and myeloperoxidase (MPO, specific for neutrophils) in samples of nasal secretion from 20 pollen-allergic subjects. All secretion samples contained measurable concentrations of both proteins. The mean ECP concentrations on two occasions without pollen exposure were 950 and 1170 micrograms/l. The ECP concentration during the pollen season without any therapy (mean 1160 micrograms/l) did not differ significantly from the baseline values, but intranasal corticosteroid therapy resulted in a significant decrease (mean 530 micrograms/l). The concentration of MPO was about 10 times higher than that of ECP, but the changes in MPO were nonsignificant throughout the observation period. An inverse correlation was found between the threshold dose in histamine challenges and the ECP level expressed either as concentration or as content. Furthermore, the ECP concentration and content 1 day after a positive allergen challenge were both significantly correlated with the strength of the challenge reaction. Measurements of ECP in nasal secretions are useful for studying the presence and activity of eosinophils in the nasal mucosa, and may prove of value in clinical investigations on patients with allergic rhinitis.     

Macrophage mannose receptor in chronic sinus disease

BACKGROUND: The role of infectious agents in the onset and maintenance of chronic sinus disease is still not fully understood. Macrophage mannose receptor (MMR), an innate pattern recognizing receptor, capable of phagocytosis of invaders and signal transduction for proinflammatory mechanisms, might be of importance in immune interactions in chronic sinus disease. OBJECTIVE: We examined the MMR in sinonasal airway mucosa to evaluate its possible role in chronic rhinosinusitis (CS) and nasal polyposis (NPs). METHODS: Surgical samples from patients with sinonasal disease were investigated with real-time RT-PCR for quantification of MMR mRNA expression, and the presence and location of MMR-positive cells was analysed by immunohistochemistry. RESULTS: Quantification of MMR mRNA showed a statistically significant higher expression in NPs compared to CS without NP and controls. Immunohistochemistry revealed expression of MMR in all tissue samples; however, in NP we found an enhanced positive cellular staining including cell aggregates. CONCLUSIONS: We could demonstrate for the first time that the expression of MMR is significantly upregulated in NP compared to patients with CS without NP or turbinate tissue of controls. Macrophages expressing MMR, accumulated in cell aggregates in NPs, play a possible key role in pathogen-macrophage interaction in NP disease.     

Histamine concentrations in nasal secretion and secretory activity in allergic rhinitis

The prerequisites for using the assayed histamine concentration in nasal secretion as an objective measure of disease activity in allergic rhinitis were investigated. It was demonstrated that in histamine determination procedures the presence of quenching substances in the nasal secretion could lead to underestimation of the histamine concentration. This bias was eliminated in a modified spectrofluorometric assay. Only an insignificant fraction of the histamine in samples collected by nasal spray washing was bound to unfiltrable particles or cells. The mean histamine concentration in nasal secretions from 15 healthy subjects was 11.2 micrograms/ml and in a group of nine patients with allergic rhinitis out of season 3.36 micrograms/ml. The histamine concentration in the latter group decreased during the pollen season and after positive allergen challenge. It is suggested that this decrease is caused by the increase in volume of the secretion during the allergic response. The use of lithium as an exogenous marker permitted quantitation of the increase in the relative amount of nasal secretion recovered by washing in the symptomatic subjects.     

Relationships between allergic inflammation and nasal airflow in children with persistent allergic rhinitis due to mite sensitization

BACKGROUND: Allergic rhinitis is associated with Th2-dependent inflammation. Nasal obstruction is the most typical symptom in children with mite allergy. OBJECTIVES: The aim of this study was to evaluate the possible relationships among nasal symptoms, allergic inflammation, including inflammatory cells and cytokine pattern, and nasal airflow in children with persistent allergic rhinitis because of mite sensitization. METHODS: Twenty children (13 males and seven females, mean age 13.4 +/- 1.6 years) with persistent rhinitis because of mite allergy were evaluated. All of them had moderate-severe grade of nasal obstruction. Total symptom score (TSS), rhinomanometry, nasal lavage, and nasal scraping were obtained in all subjects. Inflammatory cells were counted by conventional staining; interleukin (IL)-5, and IL-8 were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Eosinophils were significantly associated with TSS (R = 74.4%, P = 0.0002), with IL-5 (R = 90.6%, P < 0.0001) and with nasal flow (R = -69%, P = 0.0007), but not with IL-8 (R = 0.1%, P = 0.995). Eosinophil levels were shown to independently predict nasal flow (P < 0.001), with flow decreasing linearly for increasing eosinophils, together with a significant effect of neutrophils (P = 0.016, linear increase in flow) and a borderline effect of IL-8 (P = 0.063, linear increase in flow). CONCLUSIONS: This study demonstrates the close association between IL-5 concentration and eosinophil infiltration. In addition, there is clear evidence concerning the relationship between eosinophil infiltration and nasal airflow. Thus, nasal eosinophils can be regarded as the most important predictor of upper airway function. These findings constitute first evidence of the relationship between nasal airflow impairment and Th2-related eosinophilic inflammation in children with persistent allergic rhinitis because of mite sensitization.     

Nasal nitric oxide is increased in allergic rhinitis

Background Nitric oxide (NO) plays a major role in the regulation of vascular tone and in non-specific host defence. The epithelium in the paranasal sinuses was recently identified as the major site of NO production in the upper airways. Objective To investigate NO status in allergic rhinitis, we compared the NO concentration in the nasal cavities of control subjects (n= 19) and in patients with allergic rhinitis (n= 36) with symptoms (WS, n= 17) or without symptoms (WOS, n= 19) on the day of the test. Methods NO concentration was measured using a chemiluminescent analyser aspiring from each nasal cavity at a sampling flow rate of 0.7L/min, before and 10min after administration of a nasal vasoconstrictor. Results The mean NO concentration (± se) in the control was 235 ± 11 ppb and 225 ± 9 ppb in the right and left nostrils respectively, and was decreased by 14% and 12% by the nasal vasoconstrictor (P < 0.001). The NO concentration in patients with allergic rhinitis was significantly higher in the right and left nostrils (382 × 20 ppb and 396 ± 28 respectively, P < 0.0001 versus control). All WOS patients demonstrated normal or increased NO concentrations in both nostrils, whereas two WS patients showed decreased NO concentrations in the left nostril. Inhalation of a nasal vasoconstrictor increased NO concentration by 6% and 27% in the right and left nostrils respectively in WS patients. Conclusion Nasal NO concentration is increased in patients with allergic rhinitis. Interestingly, patients without symptoms on the day of the test also showed a clear-cut increase in nasal NO production, which could reflect a permanent inflammation of the sinus mucosa.