Risk factors and outcomes in hematological patients who acquire invasive fungal sinusitis (IFS) are infrequently reported in the modern medical era.
A retrospective study of hospitalized patients with hematological disease was conducted at National Taiwan University Hospital between January 1995 and December 2009.
Clinical characteristics and outcomes with their associated radiographic and microbiological findings were analyzed. Forty-six patients with IFS and 64 patients with chronic non-invasive sinusitis were enrolled as comparsion. IFS developed more commonly in patients with acute myeloid leukemia (AML) and with prolonged neutropenia (absolute neutrophil count less than 500/mm3 for more than 10 days) (p < 0.001). Aspergillus flavus was the most common pathogen isolated (44%). Serum Aspergillus galactomannan antigen was elevated in seven of eleven patients (64%) with IFS caused by aspergillosis but negative for all three patients with mucormycosis. Bony erosion and extra-sinus infiltration was found in 15 of 46 (33%) patients on imaging. Overall, 19 of 46 patients (41.3%) died within 6 weeks. Patients with disease subtype of AML (p = 0.044; Odds Ratio [OR], 5.84; 95% confidence interval [95% CI], 1.02-30.56) and refractory leukemia status (p = 0.05; OR, 4.27; 95% CI, 1.003-18.15) had worse prognosis. Multivariate analysis identified surgical debridement as an independent good prognostic factor (p = 0.047) in patients with IFS.
Patients of AML with prolonged neutropenia (> 10 days) had significantly higher risk of IFS. Early introduction of anti-fungal agent and aggressive surgical debridement potentially decrease morbidity and mortality in high risk patients with IFS.
Invasive fungal sinusitis (IFS) ; hematological disease; Aspergillus galactomanan
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
Breast cancer can very rarely result in late metastases to the paranasal sinuses.
Methods and results:
We present a 75-year-old woman who developed sinonasal symptoms mimicking sinusitis 20 years after receiving a breast cancer diagnosis. Rigid nasendoscopy was unremarkable, but due to persistent unilateral nasal symptoms and suspicious radiological findings, the patient underwent endoscopic biopsies of macroscopically normal sinuses which confirmed metastatic breast cancer.
High suspicion index, a thorough history, and examination are of paramount importance as metastases to the sinuses from breast cancer can occur even 20 years after diagnosis.
breast cancer; metastasis; paranasal sinuses; sphenoid; ethmoid
Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers.
To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.
Among the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type.
Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.
Inverted papilloma (IP) is a benign but locally aggressive sinonasal tumour. Aggressive surgical treatment has thus been traditionally recommended because of the risk of transformation in squamous carcinoma. CT and MRI are used to evaluate bone destruction and soft-tissue extension before surgery but may be ineffective to differentiate an inverted papilloma from squamous cell carcinoma. In recent years, F-18 Fluorodeoxyglucose positron emission tomography (18FDG-PET) is widely used as diffuse imaging procedure for diagnosis and followup of malignancy affecting the head and neck district. To evaluate the utility of 18FDG-PET/CT in the diagnosis of patients with suspicious lesions for IP, twelve patients with suspicious sinonasal inverted papilloma were selected for this study. 18FDG-PET/CT imaging was performed, and standard uptake value (SUV) was calculated for each patient. SUVmax was considered as the maximum value measured in the visualized lesions. Seven of the twelve cases exhibited uptake of 18FFDG with an SUVmax ranging from 1 to 8.1. Histopathologic diagnosis after surgery confirmed the diagnosis of IP in five cases; all these cases had an SUVmax > 3. The five cases, which exhibited absence of 18FDG uptake, had a histological diagnosis of absence of IP.
Intranasal agents play a critical role in the management of sinonasal disorders. There are ongoing efforts to develop new intranasal medications to combat sinonasal disease. Some intranasal agents, however, can have cytotoxic effects on human sinonasal tissue. In order to facilitate safe drug discovery, we developed a simple and reliable in vitro screening assay using human sinonasal explants to measure the cytotoxic profiles of intranasal agents.
We obtained sinonasal tissues from several regions of the nasal cavity from 12 patients undergoing endoscopic sinonasal surgery. These tissues were cultured on polytetrafluoroethane membrane in serum free growth medium. We determined the biochemical properties of these explants by measuring extracellular lactate dehydrogenase (LDH) levels and performing histological analyses over a period of 1–2 weeks. We then examined the cytotoxic profiles of 13 intranasal agents by measuring extracellular LDH levels using the human sinonasal explant system.
Sinonasal explants exhibited a rapid reduction in extracellular LDH levels indicating stabilization in the culture environment within 2 days. Histological analysis showed maintenance of good cellular architecture for up to 2 weeks. The explants displayed intact epithelium and expressed βIII-tubulin and Ki-67. Of the 13 tested intranasal agents, 1% zinc sulfate, 5% zinc sulfate and Zicam application were cytotoxic.
Based on the unique biochemical properties of the human nasal explant culture system, we developed a simple and reliable in vitro screening assay to determine the cytotoxic profiles of various intranasal agents by examining extracellular LDH levels and histopathology.
human sinonasal explants; drug discovery; organotypic tissue culture; intranasal agents; cytotoxicity
Survival in aplastic anemia has markedly improved in recent decades. In multivariate analysis, the introduction of newer antifungal agents and a decrease in fungal infections were independent predictors for survival in the months following immunosuppression among patients with persistent neutropenia.
Background. Persistent neutropenia associated with severe aplastic anemia (SAA) is an important risk factor for development of life-threatening infections. Earlier studies underscored the high mortality associated with invasive fungal infections (IFIs) in SAA. However, little is known about the current patterns of infections and the impact of advances in anti-infective therapy on survival in SAA.
Methods. We reviewed the records of 174 patients with SAA admitted to the Hematology Branch at NHLBI from 1989 to 2008 who were unresponsive to initial immunosuppressive therapy (IST) at 6 months. Three patient groups determined by IST protocol and time interval were compared: group 1 (43 patients; December 1989–October 1996), group 2 (51 patients; November 1996–October 2002), and group 3 (80 patients; November 2002–April 2008). Outcome variables included infections, patterns of resistance, survival, and infection-related mortality.
Results. During the past 2 decades, infection-related mortality decreased from 37% in group 1 to 11% in group 3 (P<.001), and the frequency of IFIs decreased from 49% in group 1 to 8% in group 3 (P<.001). Overall 5-year survival for all patients (n = 420) increased from 64% in group 1 to 79% in group 3 (P<.001). Among non-responders (n = 174), it increased from 23% in group 1 to 57% in group 3 (P<.001). In multivariate analysis, younger age, absolute neutrophil count >200 cells/μL before IST, absence of IFIs, and use of voriconazole were independently predictive of survival.
Conclusion. During the past 2 decades, there has been a significant decrease in IFIs, infection-related mortality, and overall mortality in patients with SAA unresponsive to initial IST.
Chronic rhinosinusitis (CRS) is a common disorder characterized by mucosal inflammation of the nose and paranasal sinuses with sinonasal symptoms persisting for greater than 12 weeks. The etiology of CRS is incompletely understood. Current understanding supports inflammation, rather than infection, as the dominant etiologic factor. CRS significantly impacts patients’ quality of life and health care expenditure. There is no standard management of CRS. Treatment strategies differ based on divergent etiologies of the various CRS subclasses. Both systemic and topical agents are used. These interventions differ in CRS with nasal polyposis (CRSwNP), CRS without nasal polyposis (CRSsNP) and specific situations such as allergic fungal rhinosinusitis or aspirin-exacerbated respiratory disease. Antibiotics are the most commonly prescribed medication for CRS, but their role in management is not strongly supported by high-level studies. This paper provides a succinct review of the evidence supporting or refuting common therapeutic agents in the management of CRS. Novel and emerging strategies will also be discussed.
review; evidence-based; sinusitis
Solitary fibrous tumors (SFTs) are uncommon neoplasms of mesenchymal origin that were first described as primary spindle-cell tumors of the pleura in 1931. Since then, infrequent case reports of extrapleural SFTs have been described including various subsites within the head and neck. Based on a review of the literature and a description of the endoscopic treatment of three patients with SFTs of the nasal cavity and ethmoid sinuses, the challenges associated with the management of sinonasal SFTs are discussed. Successful endoscopic resection was performed at a tertiary referral rhinology practice within a university center in three cases of sinonasal SFTs with no evidence of recurrence at 26, 35, and 49 months following resection. Summarized are the common presenting symptoms, appropriate diagnostic workup, and indicative computed tomography and magnetic resonance imaging appearance of SFTs. Further discussed are the challenge associated with accurate histological and immunohistochemical diagnosis, the difficulty in assessing the aggressiveness and malignant potential of these lesions, and the appropriate treatment and follow-up duration that these neoplasms require.
Solitary fibrous tumor; endoscopic resection; sinus
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
Sinonasal inverted papilloma (IP) is a primary benign lesion with a tendency for local recurrence. Malignant transformation may develop in up to 15% of cases. Fascin (Fascin 1) is an actin cross-link binding protein required for the formation of actin-based cell-surface protrusions and cell motility. Fascin up-regulation in lung, gastric, breast and hepatobiliary carcinomas correlates with aggressiveness and decreased survival. Here we evaluate immunohistochemical expression of fascin in 47 sinonasal IPs from 34 patients. Fascin over-expression is significantly more common in sinonasal IP with high-grade dysplasia than in those with no dysplastic or low-grade dysplastic epithelium (P = 0.0001). No significant change in fascin expression is seen with recurrence. Over expression of fascin in high-grade dysplastic epithelium in IP may be associated with tumor progression and malignant transformation.
Fascin; Sinonasal inverted papilloma; Dysplasia; Malignant transformation; Immunohistochemistry
Sinonasal undifferentiated carcinoma (SNUC) is an uncommon and highly aggressive neoplasm of the paranasal sinuses and nasal cavity. Its undifferentiated histologic appearance often requires immunohistochemical studies to distinguish it from other high-grade neoplasms. Due to the rarity of SNUC, its immunohistochemical staining profile has been incompletely characterized, and little work has been done on its expression of the markers for human papillomavirus (HPV). Our objective is to expand our knowledge of its immunophenotype and its association with HPV in order to define markers with mechanistic potential in the disease process, or of possible therapeutic importance. A total of five patients (one woman and four men) with SNUC, ranging in age from 26 to 75 years (mean 56.8 years) were compared to five patients (five men) with poorly differentiated squamous cell carcinoma (PDSCC), ranging in age from 53 to 75 years (mean 62.2 years). PDSCC was chosen as a control, given its well-reported immunohistochemical profile and negativity for HPV markers. The immunohistochemical panel included: CK7, CK19, EMA, NSE, chromogranin, p53, CK5/6, p63, CK14, S100, HMB-45, desmin, muscle specific actin, and CD45. Additionally, tests for p16, EBV, and HPV (subtypes 6, 11 16, 18) were performed. The diagnosis of SNUC was confirmed in all cases by histology and immunohistochemical stains. An interesting finding of strong diffuse positivity for p16 was noted in all SNUC cases, compared to only two of five PDSCC that were positive for p16. HPV DNA was not detected in any SNUC cases or any cases of PDSCC. All SNUC cases demonstrated over expression of p16 in the absence of HPV DNA expression. This may represent residual epithelial p16 staining, which is normally present in the sinonasal tract. Due to the rarity of SNUC, more cases will need to be evaluated to confirm the absence of HPV DNA.
Human papillomavirus (HPV); Sinonasal undifferentiated carcinoma (SNUC); Epstein Barr virus (EBV); Sinonasal carcinoma; Poorly differentiated squamous cell carcinoma
Significant number of patients diagnosed with chronic rhino sinusitis often tend to have a final diagnosis of fungal sinusitis. We wanted to find out (a) The incidence of patients with fungal sinusitis in those patients who were initially diagnosed as chronic rhinosinusitis. (b) The presentation of fungal sinusitis patients who were initially diagnosed as CRS. Retrospective chart review of 242 patients diagnosed as CRS from May 2006 to April 2009. The various symptoms and signs of those diagnosed initially as CRS, who were then diagnosed as fungal sinusitis were tabulated. Radiological and serological investigations were then analyzed. The microbiology of various species that were cultured in those identified as fungal sinusitis were also presented. Out of 242 patients diagnosed with CRS, 67 patients had clinical and radiological evidence of fungal sinusitis but only 24 of these patients had fungal organisms identified. Majority of them were Aspergillus fumigatus. Clinical suspicion of fungal sinusitis should be made in those patients presenting with CRS with the following signs and symptoms of nasal obstruction, discharge and polyps. Most of those fungus were Aspergillus fumigatus and responded well to treatment.
Allergic fungal rhino sinusitis; Aspergillus fumigatus
The impact of tumor differentiation on the behavior and response of sinonasal neuroendocrine carcinoma is unknown.
We performed a retrospective review of the patients treated for neuroendocrine carcinoma (NEC) of the nasal cavity or paranasal sinuses from 1992 to 2008 at MDACC.
The results of our study suggest that pathologic differentiation may not be a critical factor in the clinical management of patients with NEC of the sinonasal tract. This is in contrast to laryngeal and lung NEC for which pathological differentiation has traditionally guided clinical management.
Mutlimodality approach should be the cornerstone of treating sinonasal NEC regardless of their differentiation. Specifically, RT may provide durable local control for patients with moderately differentiated NEC if resection is not feasible or desirable, while surgical resection can benefit patients with chemo-resistant or radio-resistant disease.
Neuroendocrine carcinoma; carcinoid tumor; poorly differentiated carcinoma; sinonasal tumor
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
We sought to determine the risk of tumor incisional recurrence in patients receiving surgery and postoperative radiation therapy for locally advanced sinonasal malignancies. Medical records for 70 patients newly diagnosed with nonmetastatic American Joint Committee on Cancer stage II to stage IV sinonasal malignancies between 1991 and 2003 were retrospectively reviewed. Patient demographics and tumor variables were recorded. All patients underwent upfront surgical resection with postoperative three-dimensional conformal proton beam radiotherapy. Recurrence and survival-related outcomes were recorded. Two patients with squamous cell carcinoma had pathologically confirmed tumor recurrence at the incision site. The actuarial risk of incisional recurrence for the entire group at 1 year was 3%. One of the two patients had a maxillary sinus tumor and developed isolated skin recurrence along the transfacial incision. The other patient with an ethmoid sinus tumor developed isolated dural recurrence along the craniotomy incision. Both patients underwent multiple courses of salvage surgery and radiation therapy. One was successfully salvaged locally but developed distant metastases and the other died of local recurrence. Tumor seeding following transfacial and craniotomy surgery can occur, especially for squamous cell carcinoma. Sound oncological surgical technique, even when utilizing these difficult surgical approaches, is important to minimize incisional recurrence.
Incisional recurrence; wound metastasis; tumor implantation; anterior skull base surgery; transfacial surgery
Sinonasal mucosal melanoma is a rare and aggressive disease. The aim of this study was to analyze the clinical features of patients with sinonasal mucosal melanoma and to determine the role of Ki67 antigen as a predictor of prognosis in sinonasal mucosal melanoma.
This was a retrospective case-series study at a single institution, an academic tertiary referral center. From 1995 to 2007, 27 patients with sinonasal mucosal melanoma were reviewed retrospectively, and the expression of Ki67 antigen was assessed by immunohistochemistry.
The overall 5-yr survival rate was 33.9%. No significant differences were observed in 5-yr survival according to age, sex, stage, or the presence of melanin. The rates of local failure, regional failure, and distant failure were 37.0%, 14.8%, and 11.1%, respectively. Patients with spindle or mixed cell types had better prognoses than those with other cell types. At a cut-off value of 35%, patients with lower Ki67 scores showed better survival than those with higher Ki67 scores.
The presence of spindle or mixed cell types may indicate a better prognosis than other cell types. Ki67 immunostaining may be a useful predictor of prognosis in patients with mucosal malignant melanoma of the sinonasal tract.
Ki67 antigen; Melanoma; Nasal cavity; Paranasal sinuses
An immunocompetent 59-year-old man developed sinusitis over a 6- to 8-month period after cutting down a rotted maple tree (Acer sp.). A polypoid obstruction with a bloody drainage was evident in his right nasal cavity. A computed tomographic scan showed an opacification of the maxillary sinus. Surgery was performed to remove a fungus ball that had extended into the patient's medial sinus cavity. Sections of the sinonasal mucosa revealed marked acute and chronic sinusitis with inflammation, congestion, and hemorrhage. Sections from the pasty brown to black debrided material revealed a fungus ball consisting of an extensive network of brown-pigmented, septate, profusely branched hyphae. When grown on oat agar, the phaeoid fungus produced pycnidia and was identified as Pleurophomopsis lignicola. The genus Pleurophomopsis includes seven species, which are all known from plant material. This report documents for the first time a coelomycetous fungus, P. lignicola, causing sinusitis in an immunocompetent patient.
The diagnosis and treatment of rhinitis, sinusitis, and epistaxis during pregnancy present unique challenges to the otolaryngologist. Poorly controlled sinonasal disease may have significant adverse effects on the mother's quality of life and pregnancy outcomes and the lack of adequately controlled safety data limits the clinician's ability to make informed decisions about management. At the conclusion of this discussion, the reader should be familiar with the available literature and evidence-based guidelines regarding the safety and indications for radiographic imaging, clinical testing, medical intervention, and surgical treatment of sinonasal disease in pregnant patients. A review was performed of pertinent guidelines regarding the management of gestational rhinitis, sinusitis, and epistaxis, including the diagnostic and therapeutic limitations and physiological changes specific to pregnancy. A study population of four patients was analyzed to highlight the steps of management by reviewing the patient charts including pertinent history, physical examination, clinical course, and operative reports. Two patients with epistaxis and two patients with rhinosinusitis ranging from 27 to 38 years of age and between 16 and 35 weeks gestation were analyzed. The treatment of sinonasal disease during pregnancy is challenging and a thorough knowledge of the available medical evidence and treatment guidelines is necessary to optimize pregnancy outcomes. When the severity of disease precludes the possibility of delaying treatment, the clinician should provide a limited intervention that optimizes the mother's health without placing the fetus at significant risk.
Advair; albuterol; allergic rhinitis; amoxicillin; anaphylaxis; Augmentin; azithromycin; budesonide; epistaxis; fluticasone; gestational rhinitis; montelukast; prednisone; pyogenic granuloma; rads; rhinitis medicamentosa; rhinitis of pregnancy; sinusitis
Invasive fungal infections (IFIs) have become high prevalence in patients with hematologic malignancies. Drug-based strategies for IFIs include various approaches such as prophylactic, empiric, preemptive, and directed treatment. Prophylaxis is an attractive strategy in high-risk patients, given the lack of reliable diagnostics and the high mortality rate associated with IFIs. Prophylaxis includes the use of antifungal drugs in all patients at risk. An ideal antifungal compound for prophylaxis should have a potent and broad activity, be available both orally and intravenously, and have a low toxicity profile. Voriconazole fulfills all these criteria. The clinical efficacy of voriconazole against the majority of fungal pathogens makes it potentially very useful for the prevention of IFIs in patients with hematologic malignancies. Voriconazole appears to be very effective for the primary and secondary prevention of IFIs in these patients and recipients of allogeneic hematopoietic stem-cell transplantation. Randomized controlled trials evaluating voriconazole as primary antifungal prophylaxis in patients with neutropenia treated for a variety of hematologic malignancies have been performed, confirming its value as a prophylactic agent. Voriconazole is generally safe and well tolerated; however, its use is also associated with a number of concerns. In most patients with hematologic malignancies there is the potential for pharmacokinetic drug–drug interactions given that voriconazole is metabolized through the P450 cytochrome system.
antifungal; invasive fungal infection; prophylaxis; voriconazole
BACKGROUND AND OBJECTIVES:
Endoscopic sinus surgery (ESS), markedly improved with the introduction of new preoperative imaging techniques, intraoperative visualization tools, and the use of surgical navigation systems. In this retrospective study we evaluated the usefulness of CT-guided endscopic sinus surgery and studied its advantages over conventional endscopic sinus surgery.
We retrospectively reviewed the records of 60 randomly chosen patients with chronic rhinosinusitis (CRS) and moderate-to-severe sinonasal polyposis, undergoing endoscopic sinus surgery with surgical navigation (n=30) and without navigation (n=30). Data on the operative note, time of surgery, complications, and recurrence rate were collected and analyzed.
Of the 60 patients, 40 (66.7%) were diagnosed with CRS and 20 (33.3%) had allergic fungal sinusitis. Primary surgery was performed in 37 (61.7%) and revision surgery was performed in 23 (38.3%) cases. The computer-aided surgery (CAS) group included 28 (93.3%) patients with extensive disease and 12 (40%) with bone erosions, with intraorbital or extradural extension, while the non-CAS group included 24 (80%) patients with extensive disease and seven (23.3%) with bone erosions, with intraorbital or extradural extension. The average operative time was approximately 13 minutes greater in the navigation group, with significant improvement in the recurrence rate (n=11, 36.7% in the non-CAS group; n=5, 16.7% in the CAS group), and intraoperative complications were fewer in the CAS group (two exposures of orbital fat in the non-CAS group; no complications in the CAS group).
Computer navigational systems appear to serve as a valuable adjunct in preoperative planning and safe intraoperative dissection.
It is estimated that about 10% of the population have IgE antibodies to common inhalant molds. Exposure to fungal allergens could be linked to the presence and persistence of asthma, rhinitis and atopic dermatitis. Mold sensitization is a risk factor for development and deterioration of upper airway allergy, especially chronic rhinosinusitis. We addressed the incidence of mold allergy measured as specific IgE to molds and skin prick tests in chronic sinusitis patients. We assessed prevalence of allergic reactions to mould among surgery treated chronic sinusitis patients.
A group of 28 chronic sinusitis patients after surgery were included into the study. Routine medical examination, skin prick tests with common inhaled allergens and extended mold panel (Alternaria alternate, Cladosporium herbarium, Aspergilus fumigatus, Candida albicans, Mucor mucedo, Botrytis cinerea, Rhisopus nigricans, Penicilliumi notatum, Fusarum moniliforme Pullularia pullulans (Allergopharma, Germany), tIgE, asIgE measurement were performed (Phadia, Sweden). All investigated patients were consulted by laryngologist and mycological examination was performed.
We found that sensitization to at least one allergen was present in 43.8(14/32) of sinusitis patients. The most prevalent was sensitization to house dust mite Dermatophagoides pt., found in 21.8 % (7/32) patients. Positive results of skin prick tests with Candida albicans we observed in 18.8% (6/32), with Alternaria alternate in 15,6% (5/32), Cladosporium herbarium in 6,3% (2/32), Aspergilus fumigatus in 3,13 % (1/32). None of investigated patients presented sensitization to other mold allergens. Microbiological methods demonstrated fungal infection only in 2 patients.
Almost half of chronic sinusitis patients presented sensitization to at least one allergen. Fungal allergy is relatively rare in chronic sinusitis patients.
The surgical treatment of sinonasal malignancies is in continuous evolution. In selected patients, endoscopic resection has become a sound alternative to traditional external approaches. Further improvements are necessary to enhance the possibilities of endoscopic transnasal resection of sinonasal malignancies. We present a case of intestinal-type adenocarcinoma of the left nasal fossa eroding the skull base that affected a 56-year-old male. The patient was surgically-treated by means of a four-hand binarial endoscopic transnasal resection using a 3D endoscopic system and neuronavigation. Surgery was completed in 5 hours without significant complications. Surgeons were able to recognize and manage anatomical structures, and to control bleeding easily thanks to the bimanual technique and 3D visualization. The new 3D scopes and the bimanual technique under the guidance of a navigation system represent an interesting solution that can overcome the traditional limits of the traditional set up currently used.
Endoscopy; Skull base; Three-dimensional; Sinonasal cancer
Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust in EU. In previous small studies of this cancer, ras mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations.
We examined 174 cases of sinonasal cancer diagnosed in Denmark in the period from 1991 to 2001. To ensure uniformity, all histological diagnoses were carefully reviewed pathologically before inclusion. Paraffin embedded tumour samples from 58 adenocarcinomas, 109 squamous cell carcinomas and 7 other carcinomas were analysed for K-ras codon 12, 13 and 61 point mutations by restriction fragment length polymorphisms and direct sequencing. Information on occupational exposure to wood dust and to potential confounders was obtained from telephone interviews and from registry data.
Among the patients in this study, exposure to wood dust was associated with a 21-fold increased risk of having an adenocarcinoma than a squamous cell carcinoma compared to unexposed [OR = 21.0, CI = 8.0–55.0]. K-ras was mutated in 13% of the adenocarcinomas (seven patients) and in 1% of squamous cell carcinomas (one patient). Of these eight mutations, five mutations were located in the codon 12. The exact sequence change of remaining three could not be identified unambiguously. Among the five identified mutations, the G→A transition was the most common, and it was present in tumour tissue from two wood dust exposed adenocarcinoma patients and one patient with unknown exposure. Previously published studies of sinonasal cancer also identify the GGT → GAT transition as the most common and often related to wood dust exposure.
Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-ras mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer the found K-ras mutations, were almost exclusively G → A transitions. In conclusion, our study, based on a large representative collection of human SNC tumours, indicates that K-ras mutations are relatively infrequent, and most commonly occur in adenocarcinomas. Wood dust exposure alone was not found to be explanatory for the G→A mutations, but combination of exposure to tobacco, wood dust, and possibly other occupational agents may be a more likely explanation. Overall, the study suggests a limited role for K-ras mutations in development of sinonasal cancer.
Basaloid squamous cell carcinoma (BSCC) is a distinctive variant of squamous cell carcinoma (SCC) with more aggressive behavior. It occurs preferentially in the upper aerodigestive tract. Sinonasal tract BSCC is uncommon, and only limited studies have been reported in literature. In these studies, most BSCCs arose from the nasal mucosa with or without extension to the paranasal sinuses. Rare reported cases of BSCC involved only the paranasal sinus. In this report, we present a case of a female patient with a sphenoid sinus mass. Clinically, the patient had progressively decreasing vision and headache. Magnetic resonance imaging (MRI) and computerized tomographic (CT) scan showed an infiltrating tumor mass involving the sphenoid sinus and the sella with compression of the optic nerve. Pathologic examination revealed an invasive basaloid epithelial neoplasm that was arranged in lobules, nests and cords. The tumor also showed palisading of peripheral cells, focal abrupt squamous differentiation and in situ carcinoma in the surface mucosa. In the immunohistochemical studies, this tumor revealed a strongly positive nuclear staining for p63. The morphologic and ancillary studies indicated a BSCC. To the best of our knowledge, this is the first report of sinonasal tract BSCC that mainly involved the sphenoid bone and sella. In this region, BSCC should be distinguished from benign and malignant neoplasms that more often affect sella and base of skull, such as pituitary adenoma with extensive necrosis, small cell neuroendocrine carcinoma (SCNC), olfactory neuroblastoma, malignant germ cell tumor, paranasal adenoid cystic carcinoma (ACC), and a variety of metastatic malignancies.
Basaloid squamous cell carcinoma; Sphenoid sinus; Sellar mass