Sinusitis is a common disease in the horse. In human medicine it is described, that obstruction of the sinonasal communication plays a major role in the development of sinusitis. To get spatial sense of the equine specific communication ways between the nasal cavity and the paranasal sinuses, heads of 19 horses, aged 2 to 26 years, were analyzed using three-dimensional (3D) reformatted renderings of CT-datasets. Three-dimensional models were generated following manual and semi-automated segmentation. Before segmentation, the two-dimensional (2D) CT-images were verified against corresponding frozen sections of cadaveric heads.
Three-dimensional analysis of the paranasal sinuses showed the bilateral existence of seven sinus compartments: rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, frontal sinus, sphenopalatine sinus and middle conchal sinus. The maxillary septum divides these seven compartments into two sinus systems: a rostral paranasal sinus system composed of the rostral maxillary sinus and the ventral conchal sinus and a caudal paranasal sinus system which comprises all other sinuses. The generated 3D models revealed a typically configuration of the sinonasal communication ways. The sinonasal communication started within the middle nasal meatus at the nasomaxillary aperture (Apertura nasomaxillaris), which opens in a common sinonasal channel (Canalis sinunasalis communis). This common sinonasal channel ramifies into a rostral sinonasal channel (Canalis sinunasalis rostralis) and a caudo-lateral sinonasal channel (Canalis sinunasalis caudalis). The rostral sinonasal channel ventilated the rostral paranasal sinus system, the caudo-lateral sinonasal channel opened into the caudal paranasal sinus system. The rostral sinonasal channel was connected to the rostral paranasal sinuses in various ways. Whereas, the caudal channel showed less anatomical variations and was in all cases connected to the caudal maxillary sinus. Volumetric measurements of the sinonasal channels showed no statistically significant differences (P <0.05) between the right and left side of the head.
Under physiologic conditions both paranasal sinus systems are connected to the nasal cavity by equine specific sinonasal channels. To resolve sinus disease it is aimed to maintain or even reconstruct the normal anatomy of the sinonasal communication by surgical intervention. Therefore, the presented 3D analyses may provide a useful basis.
Horse; Computed tomography; Nasomaxillary aperture; Apertura nasomaxillaris; Upper airway; Sinonasal channel system; Paranasal sinuses
To determine whether variations in gene expression exist at multiple subsites along the sinonasal tract in patients with chronic sinusitis with polyps and in healthy controls.
Prospective, controlled study.
Academic medical center.
Subjects and Methods
Tissue expression levels of 5 genes, previously found to be characteristic of ethmoid polyps, were measured using real-time quantitative polymerase chain reaction in 100 sinonasal tissue samples. Specimens harvested from 5 regions—the ethmoid sinus, septum, inferior turbinate, middle turbinate, and lateral nasal wall—in 10 patients with chronic sinusitis and ethmoid polyps were compared to tissue from similar regions in 10 control patients without sinusitis. Western blot analysis was performed to validate differential gene expression at the protein level.
Gene expression levels of ethmoid polyps differed significantly from those of healthy ethmoid mucosa, as well as tissue from 4 surrounding anatomical sites in both patients with chronic sinusitis and controls. Alterations specific to the polyp tissue included downregulated genes, prolactin-induced protein (fold change 377.2 ± 169.0, P < .0001), and zinc α2-glycoprotein (fold change 72.1 ± 26.5, P < .0001), as well as upregulated genes, met proto-oncogene (fold change 2.5 ± 0.7, P = .029), and periostin (fold change 7.5 ± 3.4, P = .003). No significant differences in gene expression was found for neurabin 2 (fold change 1.0, P = .99).
The transcriptional pattern of ethmoid polyps appears to be unique compared with other subsites in the sinonasal cavity of patients with chronic sinusitis. Care must be taken when collecting specimens for molecular studies of the sinonasal tract to differentiate polyp from nonpolyp tissue in chronic sinusitis.
sinonasal polyposis; nasal polyp; chronic rhinosinusitis; sinusitis; periostin; met proto-oncogene; prolactin-inducible protein; zinc α2-glycoprotein; protein phosphatase 1
Facial plastic surgeons may primarily focus on esthetic improvement of the nasal shape in patients seeking rhinoplasty (RP). However, medical conditions inside the nasal cavity should not be neglected because they may lead to unresolved sinonasal problems and, hence, dissatisfaction after esthetic RP. This observational study investigated the prevalence of sinonasal symptoms and endonasal pathology in patients requesting esthetic RP.
Patients seeking RP (n = 269) were given a questionnaire evaluating nasal obstruction and sinonasal symptoms using visual analog scales and the 22-item Sino-Nasal Outcome Test. In addition, patients underwent nasal endoscopy to evaluate anatomic and/or mucosal disease and skin-prick testing in case of clinical suspicion of allergy. Two control groups consisted of patients with an otological or general ear/nose/throat problem (n = 65) and patients who planned for endoscopic sinus surgery (ESS; n = 90).
The general appraisal of nasal breathing on a scale from 0–10 in patients seeking RP was as low as 4.3 ± 3.1. Structural pathology was found in 62% of RP patients, with septal deviation being the most frequent problem encountered (54%), followed by internal nasal valve dysfunction (14%). Mucosal disease was present in 28% of RP patients. The mean SNOT-22 score of RP patients (31.8 ± 23.3) was significantly higher than the control group (11.6 ± 7.9; p < 0.001), but lower than the ESS patients (48.5 ± 22.0; p < 0.001).
The prevalence of endonasal structural or mucosal pathology in patients seeking RP is high and should not be overlooked at the time of planning surgery.
ESS; esthetic; facial; functional; mucosal disease; nasal breathing; nasal valve; revision; rhinoplasty; sinonasal
Primary sinonasal tract mucoepidermoid carcinomas (MEC) are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. The design of this study is retrospective. Nineteen cases of MEC included 10 females and 9 males, aged 15–75 years (mean, 52.7 years); males, on average were younger by a decade than females (47.2 vs. 57.7 years). Patients presented most frequently with a mass, obstructive symptoms, pain, and/or epistaxis present for a mean of 12.6 months. The majority of tumors involved the nasal cavity alone (n = 10), maxillary sinus alone (n = 6), or a combination of the nasal cavity and paranasal sinuses (n = 3) with a mean size of 2.4 cm. Most patients presented at a low clinical stage (n = 15, Stage I & II), with only 4 patients presenting with Stage III disease. Histologically, the tumors were often invasive (bone or perineural invasion), with invasion into minor mucoserous glands. Surface involvement was common. The neoplastic cells were composed of a combination of squamoid cells, intermediate cells, and mucocytes. Cystic spaces were occasionally large, but the majoritywere focal to small. Pleomorphism was generally low grade. Necrosis (n = 5) and atypical mitotic figures (n = 6) were seen infrequently. Over half of the tumors were classified as low grade (n = 11), with intermediate (n = 4) and high grade (n = 4) comprising the remainder. Mucicarmine was positive in all cases tested. Immunohistochemical studies showed positive reactions for keratin, CK5/6, p63, CK7, EMA, and CEA in all cases tested, while bcl-2 and CD117 were rarely positive. GFAP, MSA, TTF-1, and S100 protein were non-reactive. p53 and Ki-67 were reactive to a variable degree. MEC need to be considered in the differential diagnosis of a number of sinonasal lesions, particularly adenocarcinoma and necrotizing sialometaplasia. The patients were separated into stage I (n = 9), stage II (n = 6), and stage III (n = 4), without any patients in stage IV at presentation. Surgery occasionally accompanied by radiation therapy (n = 2) was generally employed. Six patients developed a recurrence, with 5 patients dying with disease (mean, 2.4 years), while 14 patients are either alive (n = 9) or had died (n = 5) of unrelated causes (mean, 14.6 years). MEC probably arises from the minor mucoserous glands of the upper aerodigestive tract, usually presenting in patients in middle age with a mass. Most patients present with low stage disease (stage I and II), although invasive growth is common. Recurrences develop in about a third of patients, who experience a shorter survival (mean, 6.5 years). The following parameters, when present, suggest an increased incidence of recurrence or dying with disease: size ≥4.0 cm (P = 0.034), high mitotic count (P = 0.041), atypical mitoses (P = 0.007), mixed anatomic site (P = 0.032), development of recurrence (P = 0.041), high tumor grade (P = 0.007), and higher stage disease (P = 0.027).
Sinonasal tract; Mucoepidermoid carcinoma; Nasal cavity; Maxillary sinus, ethmoid sinus; Frontal sinus; Review; Meta-analysis; Immunohistochemistry; Prognosis; Outcome; Staging; Differential diagnosis; Carcinoma
Sinonasal inverted papillomas (SNIPs) are derived from the benign tumors of the epithelial cells and have the potential to recur and exhibit malignant characteristics. The aim of the present study was to investigate the clinicopathological features and prognosis of patients with malignant transformation of SNIP. A total of 32 consecutive cases, who were patients at the Department of Otorhinolaryngology Head and Neck Surgery, Tianjin Huanhu Hospital from January 1991 to January 2008, were retrospectively reviewed. Survival rates and prognostic factors were calculated using the Kaplan-Meier method and multivariate Cox model survival analysis. The malignancy accounted for 8.99% of all types of SNIP. There were 25 males and seven females, and the median age of onset was 56.5 years. The sites of tumor included 22 in the nasal cavity and ethmoid sinuses, and 10 in the maxillary sinus. The tumors included 21 high-grade tumors, eight intermediate-grade tumors and three low-grade tumors. The number of patients with T1, T2, T3 and T4 stage disease was three, 10, 16 and three, respectively, according to the American Joint Committee on Cancer staging method. Based on the percentage of malignant cells in the entire tumor tissue, five patients had grade I tumors, five had grade II, eight had grade III and14 had grade IV. Among the 32 patients, three cases exhibited distant metastasis, and 19 patients underwent surgery plus postoperative radiotherapy, 10 underwent surgery alone and three underwent radiotherapy alone. The 5-year survival rate was 72.5% and the median overall survival time was 62.2 months. Kaplan-Meier univariate survival analysis indicated that the clinical stage and treatment method were prognostic factors, and multivariate Cox model survival analysis confirmed that the clinical stage and treatment method were independent factors for overall survival (relative risk: 4.211 and 0.312, respectively; P<0.05 for both). T3 and T4 staging and mono-treatment were associated with poor patient survival. Overall, the present study identified that the morbidity of SNIP-associated malignancy was low, the clinicopathological features were not specific, and the prognosis was improved compared with other types of sinonasal squamous cell carcinoma. The clinical stage and treatment method were found to affect the prognosis, and surgery plus postoperative radiotherapy was the predominant form of treatment. The present study may improve the understanding of the prognosis for patients with malignant SNIP in the future.
sinonasal tumor; inverted papilloma; malignancy; squamous cell carcinoma
Chronic rhinosinusitis (CRS) occurs at high frequency in patients with cystic fibrosis, suggesting that the cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl) ion channel might be involved in the development of chronic sinusitis in the general population. CFTR Cl ion transport controls the hydration of mucosal surfaces and promotes effective mucociliary clearance. Altered ion transport, and hence disrupted mucociliary function, could play a role in the pathogenesis of sinus disease. L-ascorbate is a metabolically active component of the nasal and tracheobronchial airway lining fluids and appears to serve as an important biological effector of CFTR-mediated chloride secretion. The purpose of this study was to determine the effects of L-ascorbate on Cl ion transport in freshly excised sinonasal epithelia from normal controls and patients with CRS.
Four different types of sinonasal tissue (normal sinus mucosa, sinus mucosa from CRS, normal nasal mucosa, nasal mucosa from CRS) were obtained during endoscopic sinus surgery and mounted on sliders with open areas of 0.03 to 0.71cm2 between Ussing hemichambers. Short-circuit current (Isc) was continuously recorded, and a serosa-to-mucosa-directed Cl gradient was applied to increase the electrochemical driving force.
L-ascorbate (500µM) stimulated Cl currents (ΔICl, µA/cm2) across sinonasal epithelia from normal and CRS patients. The Cl secretory response to L-ascorbate was effectively blocked by the Cl ion transport inhibitors glibenclamide and bumetanide. A maximal dose of L-ascorbate (at 1 mM) stimulated 53–70% of Cl currents elicited by the cAMP agonist forskolin. CRS sinonasal tissue was characterized by impaired Cl secretory responses to L-ascorbate that were reduced by 33% in sinus epithelial tissue and by 70% in nasal epithelial tissue when compared to normal subjects. In nasal epithelial tissue from normal subjects, Cl secretion was approximately 2-fold increased when compared to sinus epithelial tissue. In contrast, nasal versus sinus epithelial tissue from CRS patients showed no differences.
Topical administration of L-ascorbate to freshly excised sinus and nasal mucosa enhances chloride secretion. Given that decreased CFTR-mediated Cl secretion may contribute to the development of CRS, L-ascorbate may offer potential as a therapeutic agent for the improvement of mucociliary clearance.
ascorbate; vitamin C; chloride channel; CFTR; ion transport; chronic rhinosinusitis; Ussing chamber; epithelium
Diseases of the pediatric nose and nasal sinuses as well as neighboring anatomical structures encompass a variety of pathologies, especially of inflammatory nature. Congenital disease, such as malformations and structural deviations of the nasal septum, as well as systemic metabolic pathologies affecting the nose and sinuses, rarely require medical therapy from an Otolaryngologist.
The immunological function of the mucosa and genetic factors play a role in the development of disease in the pediatric upper airway tract, especially due to the constantly changing anatomy in this growth phase. Disease description of the nose and nasal sinuses due to mid-facial growth must also take developmental age differences (infant, toddler, preschool, and school age) into account. Epidemiological examinations and evidence based studies are often lacking in the pediatric population.
The wide range of inflammatory diseases of the nose and paranasal sinuses, such as the acute and chronic rhinosinusitis, the allergic rhinitis, and adenoid disease, play a role in the susceptibility of a child to infection. The susceptibility to infection depends on the pediatric age structure (infant, young child) and has yet to be well defined. The acute rhinosinusitis in children develops after a viral infection of the upper airways, also referred to as the “common cold” in the literature. It usually spontaneously heals within ten days without any medical therapy. Antibiotic therapy is prudent in complicated episodes of ARS. The antibiotic therapy is reserved for children with complications or associated disease, such as bronchial asthma and/or chronic bronchitis. A chronic rhinosinusitis is defined as the inflammatory change in the nasal mucosa and nasal sinus mucosa, in which the corresponding symptoms persist for over 12 weeks. The indication for CT-imaging of the nasal sinuses is reserved for cases of chronic rhinosinusitis that have been successfully treated with medication. A staged therapeutic concept is followed in CRS based on conservative and surgical methods. Nasal sinus surgery is considered nowadays as effective and safe in children. Based on the assumption that adenoids are a reservoir for bacteria, from which recurrent infections of the nose and nasal sinus originate, the adenoidectomy is still defined as a cleansing procedure in rhinosinusitis. 69.3% of the children had benefit from adenoidectomy.
Comorbidities, such as pediatric bronchial asthma, presently play an even more important role in the therapy of rhinosinusitis; therefore, it is often wise to have the support of pediatricians. In western European countries 40% of children presently suffer from allergic rhinitis, in which pronounced nasal obstruction can cause disturbed growth in facial bones. An early therapy with SIT may prevent the development of bronchial asthma and secondary sensitization to other allergens. Therefore, SIT is recommended in treatment of allergic rhinitis whenever, if possible. The assessment of diagnostic tools is for the examiner not often possible due to the lack of evidence. Rhinosurgical approaches are often described in study reports; however, they lack the standard prospective randomized long-term study design required nowadays and can only be evaluated with caution in the literature.
nose; paranasal sinuses; childhood; diseases; rhinosinusitis
The endoscopic transsphenoidal approach (eTSA) to lesions of the sellar region is typically performed jointly by neurosurgeons and otolaryngologists. Occasionally, the approach is significantly altered by sinonasal disease, anatomic variants, or previous surgery. However, there are no current guidelines that describe which physical or radiological findings should prompt a change in the plan of care. The purpose of this study was to determine the incidence of sinonasal pathology or anatomic variants noted endoscopically or by imaging that altered preoperative or intraoperative management.
A retrospective review was performed of 355 consecutive patients who underwent combined neurosurgery–otolaryngology endoscopic sella approach from August 1, 2007 to April 1, 2011. Our practice in these patients involves preoperative otolaryngology clinical evaluation and MRI review. Intraoperative image guidance is not routinely used in uncomplicated eTSA.
The most common management alteration was the addition of image guidance based on anatomic variants on MRI, which occurred in 81 patients (35.0%). Eight patients (2.9%) were preoperatively treated with antibiotics and surgery was postponed secondary to acute or chronic purulent rhinosinusitis; two (0.7%) required functional endoscopic sinus surgery for medically refractory disease before eTSA. Five patients (1.8%) required anterior septoplasty intraoperatively for severe nasal septal deviation. Two patients (0.7%) had inverted papilloma and one patient had esthesioneuroblastoma identified preoperatively during rigid nasal endoscopy.
This is one of the larger reviews of patients undergoing eTSA for sellar lesions and the only study that describes how intraoperative management may be altered by preoperative sinonasal evaluation. We found a significant incidence of sinonasal pathology and anatomic variants that altered routine operative planning; therefore, a thorough sinonasal evaluation is warranted in these cases.
Endoscopic; image-guided surgery; incidental; preoperative; sella; sinonasal; transsphenoidal
The study purpose was to detect the value of magnetic resonance imaging (MRI) compared to computed tomography (CT) and different imaging modalities as conventional radiology in evaluation of sinonasal neoplasms diagnosed by Histopathology.
Thirty patients (16 males and 14 females) were complaining of symptoms related to sinonasal tract. After thorough clinical and local examination, the patients were subjected to the following: conventional radiography, CT, MRI, and histopathological examination.
The nasal cavity was the most commonly involved site with sinonasal malignancies followed by the maxillary sinuses. The least commonly affected site was the frontal sinuses. Benign sinonasal tumors were present in 14 cases. The most common benign lesion was juvenile nasopharyngeal angiofibroma (6 cases), followed by inverted papilloma (3 cases). While malignant sinonasal tumors were present in 16 cases, squamous cell carcinoma was present in 5 cases, and undifferentiated carcinoma, in 3 cases. Lymphoepithelioma and non-Hodgkin lymphomas were present in 2 cases each, while adenocarcinoma, chondrosarcoma, adenoid cystic carcinoma, and rhabdomyosarcoma were present in 1 case each.
MRI with its superior soft tissue contrast and multiplanar capability is superior to CT in pretreatment evaluation of primary malignant tumors of sinonasal cavity.
magnetic resonance imaging; computed tomography; sinonasal tumor
Primary sinonasal tract and nasopharyngeal adenoid cystic carcinomas (STACC) are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. Eighty-six cases of STACC included 45 females and 41 males, aged 12–91 years (mean 54.4 years). Patients presented most frequently with obstructive symptoms (n = 54), followed by epistaxis (n = 23), auditory symptoms (n = 12), nerve symptoms (n = 11), nasal discharge (n = 11), and/or visual symptoms (n = 10), present for a mean of 18.2 months. The tumors involved the nasal cavity alone (n = 25), nasopharynx alone (n = 13), maxillary sinus alone (n = 4), or a combination of the nasal cavity and paranasal sinuses (n = 44), with a mean size of 3.7 cm. Patients presented equally between low and high stage disease: stage I and II (n = 42) or stage III and IV (n = 44) disease. Histologically, the tumors were invasive (bone: n = 66; neural: n = 47; lymphovascular: n = 33), composed of a variety of growth patterns, including cribriform (n = 33), tubular (n = 16), and solid (n = 9), although frequently a combination of these patterns was seen within a single tumor. Pleomorphism was mild with an intermediate N:C ratio in cells containing hyperchromatic nuclei. Reduplicated basement membrane and glycosaminoglycan material was commonly seen. Necrosis (n = 16) and atypical mitotic figures (n = 11) were infrequently present. Pleomorphic adenoma was present in 9 cases; de-differentiation was seen in two patients. Immunohistochemical studies showed positive reactions for pan-cytokeratin, CK7, CK5/6, CAM5.2, and EMA, with myoepithelial reactivity with SMA, p63, calponin, S100 protein and SMMHC. CD117, CEA, GFAP and p16 were variably present. CK20 and HR HPV were negative. STACC needs to be considered in the differential diagnosis of most sinonasal malignancies, particularly poorly differentiated carcinoma, olfactory neuroblastoma and pleomorphic adenoma. Surgery (n = 82), often accompanied by radiation therapy (n = 36), was generally employed. A majority of patients developed a recurrence (n = 52) 2–144 months after initial presentation. Overall mean follow-up was 19.4 years (range 0.4–37.5 years): 46 patients died with disease (mean 6.4 years); 5 were alive with disease (mean 5.4 years), and 35 patients were either alive or had died of unrelated causes (mean 16.3 years). ACC of the SNT is uncommon. Recurrences are common. The following parameters, when present, suggest an increased incidence of either recurrence or dying with disease: mixed site of involvement, high stage disease (stage IV), skull base involvement, tumor recurrence, a solid histology, perineural invasion, bone invasion, and lymphovascular invasion.
Adenoid cystic carcinoma; Paranasal sinuses; Nasal cavity; Staging; Prognosis; Histology; Immunohistochemistry
Data from a population based case control study in western Washington were analysed to determine whether the use of nasal sprays and drops was associated with an increased risk of sinonasal cancer. Telephone interviews were conducted with incident cases (n = 53) diagnosed between 1979 and 1983 or their next-of-kin, and with controls (n = 552) regarding their past use of nasal preparations, history of rhinologic problems, smoking history, alcohol consumption, and a number of other known or suspected risk factors. Both cigarette smoking and alcohol consumption were associated with an increased risk of sinonasal cancer; the strongest associations were found with squamous cell tumours. Subjects who reported a history of nasal preparation use were 3.5 times (95% confidence interval = 1.7-7.0) more likely than non-users to develop sinonasal cancer. The risk of sinonasal cancer increased with increasing duration of use of nasal preparations. These findings suggest the need for a more detailed investigation of the possible adverse consequences of long-term use of nasal preparations.
In general, the etiologic factors of chronic paranasal sinusitis are systemic conditions such as nutrition, predisposition, allergy, and local factors such as nasal anatomic conditions. Among these factors, the development of unilateral sinusitis is a model case verifying the influence of local factors. In my study of 640 cases over a certain period of time, a comparison was made between 161 cases of unilateral sinusitis and 479 cases of bilateral sinusitis in order to verify the effects of local factors in the development of this disease. Patients with a history of previous sinus surgery or tumors were eliminated from the cases. 1. The male-female incidence rate, and the age distribution of the patients at the initial visit showed no prominent differences between unilateral and bilateral cases. 2. It was found that a larger number of cases of unilateral sinusitis had a duration of less than one year as compared to bilateral sinusitis which were longer than and year. Therefore it can be said that the duration of unilateral sinusitis is usually shorter than that of bilateral sinusitis. 3. In unilateral cases the patients with moderate to severe nasal septal deviation, one number of patients with septal deviation towards the diseased side was twice as high as that on the non-affected side. 4. The incidence rate of polyps occurring in the middle meatus was shown to be about twice as high in bilateral cases as in unilateral cases.(ABSTRACT TRUNCATED AT 250 WORDS)
The Ewing’s family of tumors (EFT) are malignant neoplasms affecting children and young adults. Most cases arise in the long bones or the pelvis. Primary EFT of head and neck is uncommon and primary sinonasal EFT is even rarer. Previous studies have not focused on the sinonasal region specifically, and the published literature on sinonasal EFT consists of sporadic case reports. Fourteen cases of sinonasal EFT were available and had H&Es for review and immunohistochemical stains for CD99, S100, keratins, synaptophysin and desmin. FISH or RT-PCR was performed for EWSR1 abnormalities on 8 cases. The 14 identified patients included 5 males and 9 females, ranging from 7–70 years of age (mean 32.4 years). Tumors involved nasal cavity (5), sinuses (5) or both (4). Five patients had dural, orbital or brain involvement. The majority involved bone radiologically and/or microscopically. All cases were composed of small cells with variable cytoplasmic clearing. Focal or prominent nesting was noted in most cases. All cases were positive for CD99. Keratins (AE1/3 and/or CAM5.2), S100 and synaptophysin were positive in 4, 3 and 5 cases, respectively. All cases were negative for desmin. The 8 cases tested by FISH or RT-PCR were positive for EWSR1 abnormalities. Follow-up in 8 patients ranged from 1–168 months (average 11.3 m) showing 1 death due to metastatic disease, 1 death due to local disease, 1 patient alive with metastases and 5 patients disease-free at last follow-up. Interestingly, however, an analysis of the literature suggests a better prognosis for sinonasal EFT than EFT overall.
Ewing’s family of tumors; Sinonasal; Maxillary bone; Olfactory neuroblastoma
Decreased epithelial expression of mRNA for S100A7 (Psoriasin) and S100A8/A9 (Calprotectin) have been reported in chronic rhinosinusitis (CRS).
To assess whether the expression of S100 proteins is also altered in the sinonasal cavity of patients with CRS.
We determined levels of S100 proteins in nasal lavage and sinonasal tissue extracts from CRS patients using ELISA and immunohistochemical analysis of nasal polyp tissue from CRSwNP patients and uncinate tissue from all three groups.
Expression levels of S100 proteins were decreased compared to control subjects in nasal lavage fluids from both CRS groups (p < 0.05). Similarly, tissue expression of these proteins assessed by immunohistochemistry demonstrated clear reductions primarily in the epithelial lining. Interestingly, levels of Calprotectin were increased in nasal polyp tissue despite lower levels in lavage fluid. Levels of Calprotectin in nasal tissues were correlated with levels of neutrophils as assessed by quantification of neutrophil elastase.
Several S100 proteins are in the epidermal differentiation complex of genes and have been demonstrated to play a role in maintenance of barrier function and formation of an antimicrobial shield. We demonstrate significantly decreased levels of expression of S100 proteins in epithelium of CRS patients, which may lead to diminished innate immune response and barrier function. Increased levels of Calprotectin in nasal polyp tissue may reflect neutrophil recruitment and a compensatory mechanism. Future studies will be important to determine whether reduced levels of S100 proteins lead to decreased antimicrobial responses in the upper airways and sinuses and whether this reduction plays an etiologic role in CRS pathogenesis and susceptibility to infectious disease.
Chronic Rhinosinusitis; S100A7; S100A8/A9; Psoriasin; Calprotectin; Epithelium; Barrier; Epidermal Differentiation Complex
In cystic fibrosis (CF), the paranasal sinuses are sites of first and persistent colonization by pathogens such as Pseudomonas aeruginosa. Pathogens subsequently descend to the lower airways, with P. aeruginosa remaining the primary cause of premature death in patients with the inherited disease. Unlike conventional aerosols, vibrating aerosols applied with the PARI Sinus™ nebulizer deposit drugs into the paranasal sinuses. This trial assessed the effects of vibrating sinonasal inhalation of the antibiotic tobramycin in CF patients positive for P. aeruginosa in nasal lavage.
To evaluate the effects of sinonasal inhalation of tobramycin on P. aeruginosa quantification in nasal lavage; and on patient quality of life, measured with the Sino-Nasal Outcome Test (SNOT-20), and otologic and renal safety and tolerability.
Patients were randomized to inhalation of tobramycin (80 mg/2 mL) or placebo (2 mL isotonic saline) once daily (4 minutes/nostril) with the PARI Sinus™ nebulizer over 28 days, with all patients eligible for a subsequent course of open-label inhalation of tobramycin for 28 days. Nasal lavage was obtained before starting and 2 days after the end of each treatment period by rinsing each nostril with 10 mL of isotonic saline.
Nine patients participated, six initially receiving tobramycin and three placebo. Sinonasal inhalation was well tolerated, with serum tobramycin <0.5 mg/L and stable creatinine. P. aeruginosa quantity decreased in four of six (67%) patients given tobramycin, compared with zero of three given placebo (non-significant). SNOT-20 scores were significantly lower in the tobramycin than in the placebo group (P=0.033).
Sinonasal inhalation of vibrating antibiotic aerosols appears promising for reducing pathogen colonization of paranasal sinuses and for control of symptoms in patients with CF.
PARI Sinus; nasal lavage; SNOT-20; cystic fibrosis; Pseudomonas aeruginosa; sinonasal; upper airways
Sinonasal epithelial cells participate in host defense by initiating innate immune mechanisms against potential pathogens. Antimicrobial innate mechanisms have been shown to involve Th1-like inflammatory responses. Although epithelial cells can also be induced by Th2 cytokines to express proeosinophilic mediators, no environmental agents have been identified that promote this effect.
Human sinonasal epithelial cells from patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls were harvested and grown in primary culture. Cell cultures were exposed to a range of concentrations of chitin for 24 hours, and mRNA for acidic mammalian chitinase (AMCase), eotaxin-3, and thymic stromal-derived lymphopoietin (TSLP) were assessed. Other cultures were exposed to interleukin 4 (IL- 4) alone and in combination with dust-mite antigen (DMA) for 36 hours. Extracted mRNA and cell culture supernatant were analyzed for expression of AMCase and eotaxin-3.
Chitin induced a dose-dependent expression of AMCase and eotaxin-3 mRNA but not TSLP. Patients with recalcitrant CRSwNPs showed lower baseline expression of AMCase when compared with treatment-responsive CRSwNP and less induction of AMCase expression by chitin. DMA did not directly induce expression of AMCase or eotaxin-3. Expression of eotaxin-3 was stimulated by IL-4 and further enhanced with the addition of DMA. Levels of AMCase were not significantly affected by either IL-4 or DMA exposure. In some cases, the combination of IL-4 and DMA was able to induce AMCase expression in cell cultures not producing AMCase at baseline.
The abundant biopolymer chitin appears to be recognized by a yet uncharacterized receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase and eotaxin-3, two pro-Th2 effector proteins. This finding suggests the existence of a novel innate immune pathway for local defense against chitin-containing organisms in the sinonasal tract. Dysregulation of this function could precipitate or exacerbate Th2 inflammation, potentially acting as an underlying factor in recalcitrant CRSwNP.
Acidic mammalian chitinase; cell culture; chitin; eosinophils; epithelial cell; rhinitis; rhinosinusitis; sinonasal; Th2
The aim of this study is to investigate the role of platelet-derived growth factor (PDGF) in the pathogenesis of sinonasal polyps.
Study group (groups 1-3) consisted of nasal polyp samples of patients with sinonasal polyps and the control group consisted of inferior turbinate samples of patients without nasal polyp. In group 1, 14 specimens from ethmoid sinus; in group 2, 10 specimens from nasal cavity; in group 3, 10 specimens from maxillary sinus; and in group 4 (control), 9 specimens from inferior turbinate were included. By immunohistochemical staining technique, the PDGF positivity index (PI) in mucosal layers and in the inflammatory cells were assessed at the epithelium (EP), subepithelial layer of lamina propria (SE), and deep paraglandular layer of the mucosa (D).
Polymorphonuclear cell (PMNC)-percentage (%) values of ethmoid and maxillary sinus, and the PDGF PI from all cells of ethmoid sinus and nasal cavity were significantly higher than those of the control group. As mononuclear cell-% (MNC-%) increased, the PDGF_EP_basal PI, PDGF_SE_endothelial PI, and PDGF_D_endothelial PI decreased. As PMNC-PDGF PI increased, the PDGF_D_perivascular PI decreased and PDGF_D_endothelial PI increased. As PDGF-MNC PI increased, the PDGF_EP_apical PI, PDGF_SE_endothelial PI, and PDGF_D_endothelial PI decreased. As PDGF-all cells (PMNCs, MNCs, and fibroblasts) PI increased, the PDGF_EP_basal PI and PDGF_D_endothelial PI decreased, and the PDGF_D_perivascular PI increased.
We concluded that the PDGF systems play important roles in polyp pathogenesis. Fibroblast-derived PDGF may be more important than MNC-derived PDGF in polyp developing process. Increased perivascular-PDGF-PI in deep layers of the mucosa may result in sinonasal polyp formation by causing an increase in vascular permeability and extracellular edema, and thus promoting migration of inflammatory cells to extracellular area. Tissue oxygenization may be important for the initiation of PDGF release system. Because of this reason, nasal obstruction should be medically treated earlier, and, if necessary, by surgical approaches.
Sinonasal polyp; Pathogenesis; Platelet-derived growth factor; Perivascular; Endothelial
Mucosal leishmaniasis (ML) is a progressive disease that affects cartilage and bone structures of the nose and other upper respiratory tract structures. Complications associated with ML have been described, but there is a lack of studies that evaluate the structural changes of the nose and paranasal sinuses in ML using radiological methods. In this study, we aimed to assess the opacification of the paranasal sinuses in patients with treated ML and any anatomical changes in the face associated with ML using multidetector computed tomography scans (MDCT) of the sinuses. We compared the findings with a control group.
We evaluated 54 patients with treated ML who underwent CT scans of the sinuses and compared them with a control group of 40 patients who underwent orbital CT scans. The degree of sinus disease was assessed according to the Lund-Mackay criteria. Forty of the 54 patients with a history of ML (74.1%) had a tomographic score compatible with chronic sinusitis (Lund-Mackay ≥4). CT scans in the leishmaniasis and control groups demonstrated significant differences in terms of facial structure alterations. Patients from the ML group showed more severe levels of partial opacification and pansinus mucosal thickening (42.6%) and a greater severity of total opacification. Patients from the ML group with a Lund-Mackay score ≥4 presented longer durations of disease before treatment and more severe presentations of the disease at diagnosis.
CT scans of the sinuses of patients with ML presented several structural alterations, revealing a prominent destructive feature of the disease. The higher prevalence in this study of chronic rhinosinusitis observed in CT scans of patients with treated ML than in those of the control group suggests that ML can be considered a risk factor for chronic rhinosinusitis in this population (p<0.05).
Mucosal leishmaniasis (ML) is mainly caused by the agent Leishmania (V.) brasiliensis and usually occurs months or years after symptomatic or asymptomatic skin infection. Approximately 5% of patients with untreated cutaneous leishmaniasis will develop ML, a presentation that causes significant morbidity in patients. This important but often neglected anthropozoonosis also presents direct health care costs and several indirect losses in terms of impaired daily functioning. In this study, we aimed to assess the degree of opacification of the paranasal sinuses in patients with treated ML and any anatomical changes in the face associated with ML using multidetector computed tomography scans (MDCT) of the sinuses. We compared the findings in this population with those from a control group. We evaluated 54 patients with treated ML who were subjected to MDCT of the sinuses and compared them with a control group of 40 patients who underwent MDCT of the orbit. CT scans of the sinus of patients with ML presented several structural alterations, revealing a prominent destructive feature of the disease. The higher prevalence of chronic rhinosinusitis observed in CT scans of patients with treated ML in this study also suggests that ML can be considered a risk factor for chronic rhinosinusitis in this population.
Background: Chronic rhino sinusitis (CRS) is the most common disease for which consultation of otorhinolaryngologist is sought. The approach to patients with chronic rhino sinusitis is endoscopic surgery which aims at removing the obstruction of the main drainage pathway. The osteomeatal complex based essentially on the concept that such obstruction perpetuates the sinus disease. This in turn requires the surgeons to have detailed knowledge of the anatomy of the lateral nasal wall, paranasal sinuses and surrounding vital structures and of the large number of anatomical variants in the region.
Aim: To study anatomical variations of osteomeatal complex in chronic sinusitis patients.
Materials and Methods: Descriptive cross-sectional study design in which 54 consecutive cases of chronic rhino sinusitis patients attending the ENT outpatient department, who had chronic sinusitis for more than three months duration not responding to the medical line of treatment and who were willing to undergo Functional Endoscopic Sinus Surgery satisfying the inclusion criteria were studied. The results were expressed in percentage and proportions.
Results: In our study it was observed that 53.7% of the chronic sinusitis cases had two or more anatomical variations and 33.3% of the cases had single anatomical variation. Deviated nasal septum was found to be the most common amongst the anatomical variations in chronic sinusitis cases in the present study which was followed by unilateral concha bullosa and paradoxically bent middle turbinate. Agger nasi cell and Haller cell were seen in one case each.
Conclusion: Prevalence of multiple anatomical variations was more in our study in comparison to single anatomical variation. Deviated nasal septum was the most common anatomical variation encountered in our study followed by concha bullosa.
Chronic rhino sinusitis; FESS; Osteomeatal complex; Paranasal sinuses
1). To be able to recognize allergic fungal sinusitis (AFS), a common and underdiagnosed condition.
A 28 years old man presented with yet another flare up of chronic sinusitis (he also had a history of allergic rhinitis), complaining of impaired taste and smell, itching in ears, and minimal epistaxis—mainly on the right side—after blowing his nose. The physical exam revealed a hyperemic nasal mucosa smeared with bright red blood and covered with yellowish crusts. The right inferior turbinate was pink and swollen. Investigations: skin prick test for Curvularia lunata was positive, white blood cell count was 7.700, with 9% eosinophils (with an absolute eosinophil count of 704), radio-allergo-sorbent test for Curvularia lunata was positive, total serum immunoglobulin E was 1926 IU/ml, serum eosinophilic cationic protein was 80 micrograms/l. A CT scan of the sinuses revealed pansinusitis and a soft tissue process (with multiple areas of calcification) in the right maxillary sinus eroding through the supero-medial wall into the right orbit. The patient was treated surgically. Analysis of debrided tissue revealed on histology large amounts of eosinophil-rich mucoid material, necrosis and bone remodeling. The bacterial smears and tissue cultures were negative. The silver impregnation stain revealed fungal short hyphal elements. Tissue fungal cultures grew Curvularia lunata.
Although responsible for many cases of chronic rhino-sinusitis, AFS is heavily underdiagnosed. We present a case with some unusual features. Our patient had AFS, which tends to affect patients with significant immune deficiencies (our patient was immunocompetent).
The invasion into orbit (usually a disastrous complication) was discovered only as accidental finding on a CT scan.
Positive radioallergosorbent test (RAST) results, skin test results, or presence of serum precipitins for fungal allergens, in combination with fungal culture results that match that particular fungal species, are crucial in making a diagnosis of allergic fungal sinusitis.
Some believe that allergic fungal sinusitis may be a trigger of chronic rhinosinusitis in up to 93% of cases. Taking into consideration the lack of specificity of nasal eosinophilia, and the ubiquicity of fungal colonization of the nose, it has been proposed to apply the term AFS only to those patients with chronic rhinosinusitis that fulfill the above criteria. Therapy is surgical.
CFTR is a dynamically regulated anion channel. Intracellular WNK1-SPAK activation causes CFTR to change permeability and conductance characteristics from a chloride-preferring to bicarbonate-preferring channel through unknown mechanisms. Two severe CFTR mutations (CFTRsev) cause complete loss of CFTR function and result in cystic fibrosis (CF), a severe genetic disorder affecting sweat glands, nasal sinuses, lungs, pancreas, liver, intestines, and male reproductive system. We hypothesize that those CFTR mutations that disrupt the WNK1-SPAK activation mechanisms cause a selective, bicarbonate defect in channel function (CFTRBD) affecting organs that utilize CFTR for bicarbonate secretion (e.g. the pancreas, nasal sinus, vas deferens) but do not cause typical CF. To understand the structural and functional requirements of the CFTR bicarbonate-preferring channel, we (a) screened 984 well-phenotyped pancreatitis cases for candidate CFTRBD mutations from among 81 previously described CFTR variants; (b) conducted electrophysiology studies on clones of variants found in pancreatitis but not CF; (c) computationally constructed a new, complete structural model of CFTR for molecular dynamics simulation of wild-type and mutant variants; and (d) tested the newly defined CFTRBD variants for disease in non-pancreas organs utilizing CFTR for bicarbonate secretion. Nine variants (CFTR R74Q, R75Q, R117H, R170H, L967S, L997F, D1152H, S1235R, and D1270N) not associated with typical CF were associated with pancreatitis (OR 1.5, p = 0.002). Clones expressed in HEK 293T cells had normal chloride but not bicarbonate permeability and conductance with WNK1-SPAK activation. Molecular dynamics simulations suggest physical restriction of the CFTR channel and altered dynamic channel regulation. Comparing pancreatitis patients and controls, CFTRBD increased risk for rhinosinusitis (OR 2.3, p<0.005) and male infertility (OR 395, p<<0.0001). WNK1-SPAK pathway-activated increases in CFTR bicarbonate permeability are altered by CFTRBD variants through multiple mechanisms. CFTRBD variants are associated with clinically significant disorders of the pancreas, sinuses, and male reproductive system.
Genetic disorders of ion channels can affect the body's ability to function properly in many ways. CFTR, an ion channel regulating movement of chloride and bicarbonate across cell membranes, is important for absorbing and secreting fluids. If the gene responsible for the CFTR channel is mutated severely, the result is cystic fibrosis, a hereditary disorder in which the patient develops thick mucus, especially in the lungs, as well as scarring (fibrosis) in the pancreas. Cystic fibrosis also affects the sweat glands, nasal sinuses, intestines, liver, and male reproductive system. Mutations to the CFTR gene that do not cause cystic fibrosis have been considered benign. However, we discovered 9 CFTR mutations that do not cause cystic fibrosis but do cause inflammation and scarring of the pancreas (chronic pancreatitis). These mutant CFTR channels secrete chloride, which is important in the sweat glands, lungs, and intestines, but not bicarbonate, which is important in the pancreas, sinuses, and male reproductive tract. We found patients with any of these 9 mutations had chronic pancreatitis, and often sinus infections, and male infertility, but not other symptoms of cystic fibrosis. Our computer models and data will help researchers develop better drugs and help physicians treating patients with chronic pancreatitis.
Background We have described an unusual sinonasal neoplasm which is a histological mimic of renal cell carcinoma (RCC) and coined the nosological classification “sinonasal renal cell-like adenocarcinoma” (SRCLA) to describe this unusual entity. Since the original description (Zur et al. Otolaryngol Head Neck Surg 128:441–7, 2002), we have reviewed the case reported by Moh’d Hadi et al. (Rhinology 40:44–7, 2002) and have seen two new cases in consultation. Our purpose here is to describe the additional cases and to extend the reported outcome for these patients. Design Four patients were identified. Slides and immunohistochemistry results were reviewed in consultation. Updated clinical follow-up was obtained from the respective clinicians. Results This group consisted of three women, one man, 22–69 years, and mean 46. Three tumors were in the nasal cavity and one was in the nasopharynx. Histologically, these tumors were uniformly composed of clear cells, forming either solid or glandular patterns. The tumor cells were cuboidal to polyhedral; transition to short spindle cells was seen in one case. One case revealed moderate nuclear pleomorphism. No perineural or vascular invasion, or necrosis was seen. No mucin-producing or squamous elements were seen. Immunohistochemistry (IHC) revealed the following staining profile: CK7 + (4/4), CK20 + (focal 1/4), S100 + (1/4), and CD10 + (1/2). No staining was seen for vimentin (0/4), RCC (0/2), thyroglobulin (0/2), actin (0/2), or calponin (0/2). Three patients were treated primarily with surgery, two patients also received adjuvant radiotherapy (RT); the fourth patient was treated with primary RT. All patients are disease-free, based on endoscopy and/or radiography, 2, 4, 5 and 8 years after diagnosis. Renal cell carcinoma has not been identified in any patient. Conclusion Sinonasal renal cell-like adenocarcinoma is a rare and distinct entity noteworthy in its resemblance to RCC. Immunohistochemistry can easily distinguish between these two tumors. No patient developed recurrent or metastatic disease, or was found to have RCC. Greater experience will allow us to fully understand its long-term behavior and arrive at more standardized therapeutic recommendations.
Sinonasal; Renal cell carcinoma; Renal cell-like carcinoma; Vermeer
Chronic rhinosinusitis (CRS) is a major cause of concern worldwide. Nasal septal deviation (NSD) may either cause osteomeatal obstruction or may interfere with proper airflow and potentially predispose to sinusitis. Due to the lack of a universally accepted classification on NSD it has not been established whether NSD influences the development of sinusitis or not. Mladina in 1987 proposed a classification in which he classified NSD into seven different categories. The aims and objectives of this study are to observe the correlation between NSD and CRS and to study the relation of different grades of NSD with sinusitis as per Mladina's classification. Patients above 18 years of age presenting to ENT OPD with complaint of nasal obstruction, nasal discharge and headache were subjected to CT scan (nose and paranasal sinuses) coronal section with contiguous 5 mm thickness slice perpendicular to the hard palate in prone position. Presence of NSD and sinusitis was observed. 120 cases were studied. The mean age was 28.7 ± 9.37 years with age range 18–58 years. There were 92 (76.6 %) males and 28 (23.3 %) females with a M:F ratio of 3:1. Out of 120 cases, 114 (95 %) cases had NSD. Sinusitis was present in 63 (52.5 %) cases on CT scan. Out of 57 (50.0 %) cases with NSD and sinusitis, 13 (11.4 %) cases had sinusitis on the same side of NSD, 14 (12.28 %) cases had sinusitis on the side opposite to NSD and 30 (26.31 %) cases had sinusitis on both sides of NSD. There was no statistically significant relationship between NSD and sinusitis. As per Mladina's classification vertical deviations accounted for majority of patient’s septal deviations with 31 (27.1 %) cases of type II NSD and 24 (21.1 %) cases of type I NSD. The maximum number of cases with sinusitis had vertical deviations with type I NSD in 17 (27.0 %) cases and type II NSD in 18 (28.5 %) cases. The present study reveals that there is no correlation between NSD and sinusitis. Vertical deviations type I and type II are more prone to sinusitis as they involve the nasal valve area.
Deviated septum; Rhinosinusitis
Disorders of the nose and paranasal sinuses are among the most common chronic illnesses. Although considerable progress has been made in the medical and surgical control of these diseases, a large number of questions relating to the diagnosis, evaluation, and treatment of these conditions remain unanswered. The aim of the present study was to evaluate differences in the frequency of symptoms and disease severity in patients with nasal septal deviation (NSD) compared with chronic rhinosinusitis (CRS).
Materials and Methods:
A total of 156 patients, divided into NSD and CRS groups, were studied in relation to symptoms and disease severity. Patients were selected from those referred to the Ear, Nose, and Throat (ENT) Wards of the Imam Reza and Ghaem Hospitals, who had not responded to a variety of treatments. Depending on the type of disease, patients were candidates for either septoplasty or endoscopic sinus surgery. The Rhinosinusitis Symptom Inventory was administered to measure the severity of symptoms, with scores assigned based on the answers given by patients (Likert scale). Scores were compared between the CRS and NSD groups.
A total of 156 patients (78 with NDS and 78 with CRS) entered the study in overall sinonasal symptoms were more prevalent in CRS group. Nasal congestion, runny nose, earache, toothache, and smelling disorder were significantly more common in the CRS group (P<0.001); while there were no significant differences in symptoms such as facial pressure, fever, or headache between the two groups (P>0.05).
Patients with CRS manifested statistically significantly greater sinonasal symptom scores than patients with NSD.
Chronic rhinosinusitis; Septal deviation; Symptoms of sinonasal disease
To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects.
Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST.
Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR).
Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted.