Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma.

Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics. We performed target-capture sequencing of plasma EBV DNA and identified differences in the abundance and size profiles of EBV DNA molecules within plasma of NPC and non-NPC subjects. NPC patients had significantly higher amounts of plasma EBV DNA, which showed longer fragment lengths. Cutoff values were established from an exploratory dataset and tested in a validation sample set. Adopting an algorithm that required a sample to concurrently pass cutoffs for EBV DNA counting and size measurements, NPCs were detected at a positive predictive value (PPV) of 19.6%. This represented superior performance compared with the PPV of 11.0% in the prospective screening study, which required participants with an initially detectable plasma EBV DNA result to be retested within 4 weeks. The observed differences in the molecular nature of EBV DNA molecules in plasma of subjects with or without NPC were successfully translated into a sequencing-based test that had a high PPV for NPC screening and achievable through single time-point testing.

Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer.

BACKGROUND: Circulating cell-free Epstein-Barr virus (EBV) DNA is a biomarker for nasopharyngeal carcinoma. We conducted a prospective study to investigate whether EBV DNA in plasma samples would be useful to screen for early nasopharyngeal carcinoma in asymptomatic persons. METHODS: We analyzed EBV DNA in plasma specimens to screen participants who did not have symptoms of nasopharyngeal carcinoma. Participants with initially positive results were retested approximately 4 weeks later, and those with persistently positive EBV DNA in plasma underwent nasal endoscopic examination and magnetic resonance imaging (MRI). RESULTS: A total of 20,174 participants underwent screening. EBV DNA was detectable in plasma samples obtained from 1112 participants (5.5%), and 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently positive results on the repeated sample. Among these 309 participants, 300 underwent endoscopic examination, and 275 underwent both endoscopic examination and MRI; of these participants, 34 had nasopharyngeal carcinoma. A significantly higher proportion of participants with nasopharyngeal carcinoma that was identified by screening had stage I or II disease than in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test) and had superior 3-year progression-free survival (97% vs. 70%; hazard ratio, 0.10; 95% confidence interval, 0.05 to 0.18). Nine participants declined to undergo further testing, and 1 of them presented with advanced nasopharyngeal carcinoma 32 months after enrollment. Nasopharyngeal carcinoma developed in only 1 participant with negative EBV DNA in plasma samples within 1 year after testing. The sensitivity and specificity of EBV DNA in plasma samples in screening for nasopharyngeal carcinoma were 97.1% and 98.6%, respectively. CONCLUSIONS: Analysis of EBV DNA in plasma samples was useful in screening for early asymptomatic nasopharyngeal carcinoma. Nasopharyngeal carcinoma was detected significantly earlier and outcomes were better in participants who were identified by screening than in those in a historical cohort. (Funded by the Kadoorie Charitable Foundation and the Research Grants Council of the Hong Kong government; ClinicalTrials.gov number, NCT02063399 .).

Distinguishing early-stage nasopharyngeal carcinoma from benign hyperplasia using intravoxel incoherent motion diffusion-weighted MRI.

OBJECTIVES: MRI can detect early-stage nasopharyngeal carcinoma (NPC), but the detection is more challenging in early-stage NPCs because they must be distinguished from benign hyperplasia in the nasopharynx. This study aimed to determine whether intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) MRI could distinguish between these two entities. METHODS: Thirty-four subjects with early-stage NPC and 30 subjects with benign hyperplasia prospectively underwent IVIM DWI. The mean pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and apparent diffusion coefficient (ADC) values were calculated for all subjects and compared between the 2 groups using Student's t test. Receiver operating characteristics with the area under the curve (AUC) was used to identify the optimal threshold for all significant parameters, and the corresponding diagnostic performance was calculated. A p value of < 0.05 was considered statistically significant. RESULTS: Compared with benign hyperplasia, early-stage NPC exhibited a significantly lower D mean (0.64 ± 0.06 vs 0.87 ± 0.11 × 10-3 mm2/s), ADC0-1000 mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10-3 mm2/s), ADC300-1000 (0.63 ± 0.05 vs 0.86 ± 0.10 × 10-3 mm2/s) and a higher D* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10-3 mm2/s) (all p < 0.001). No significant difference in the f mean was observed between the two groups (p = 0.216). The D and ADC300-1000 mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10-3 mm2/s yielded the highest sensitivity, specificity and accuracy (100%, 93.3% and 96.9%, respectively) in distinguishing early-stage NPC from benign hyperplasia. CONCLUSION: DWI has potential to distinguish early-stage NPC from benign hyperplasia and D and ADC300-1000 mean were the most promising parameters. KEY POINTS: • Diffusion-weighted imaging has potential to distinguish early-stage nasopharyngeal carcinoma from benign hyperplasia in the nasopharynx. • The pure diffusion coefficient, pseudo-diffusion coefficient from intravoxel incoherent motion model and apparent diffusion coefficient from conventional diffusion-weighted imaging were significant parameters for distinguishing these two entities in the nasopharynx. • The pure diffusion coefficient, followed by apparent diffusion coefficient, may be the most promising parameters to be used in screening studies to help detect early-stage nasopharyngeal carcinoma.

Narrow band imaging endoscopy of the nasopharynx is not more useful than white light endoscopy for suspected nasopharyngeal carcinoma.

Endoscopy is often used to screen for nasopharyngeal carcinoma. A normal nasopharynx on white light endoscopy may yet harbor subclinical or occult malignancy. This study assessed whether the vascular pattern seen on narrow band imaging endoscopy could indicate this and thus be useful for detecting suspected nasopharyngeal carcinoma. The nasopharynx of 156 patients who failed serological screening for or presented with symptoms of nasopharyngeal carcinoma was graded under white light and narrow band imaging endoscopy and a biopsy taken. The accuracy of assessing the nasopharynx as being probably or definitely malignant on white light endoscopy was high (area under the curve = 0.924), as it was of being normal on narrow band imaging endoscopy (=0.799). The sensitivity and specificity of white light and narrow band imaging endoscopy for nasopharyngeal carcinoma was 93 and 22 %, and 92 and 98 %, respectively. Significantly associated with nasopharyngeal carcinoma was a high index of suspicion or definitely malignant grade on white light endoscopy (p < 0.0005, odds 58.978) and vascular tufts on narrow band imaging endoscopy (p = 0.020, odds 41.210). Narrow band imaging endoscopy of vasculature alone for suspected nasopharyngeal carcinoma is not more useful than white light endoscopy of nasopharyngeal morphology, nor does it add to or surpass the diagnostic accuracy of white light endoscopy in this regard.

Early detection of nasopharyngeal carcinoma: performance of a short contrast-free screening magnetic resonance imaging.

BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.

Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is prevalent in Southeast Asia. Over the last decade, plasma Epstein-Barr virus (EBV) DNA has been developed as a tumor marker for NPC. In this study, the authors investigated whether plasma EBV DNA analysis is useful for NPC surveillance. METHODS: In total, 1318 volunteers ages 40 to 60 years were prospectively recruited. Plasma EBV DNA and serology for viral capsid antigen immunoglobulin A (IgA) were measured. Participants who had detectable plasma EBV DNA or positive IgA serology underwent nasal endoscopic examination and a follow-up plasma EBV DNA analysis in approximately 2 weeks. All participants were followed for 2 years to record the development of NPC. RESULTS: Three individuals with NPC were identified at enrolment. All of them were positive for EBV DNA and remained positive in follow-up analysis. Only 1 of those patients was positive for EBV serology. In 1 patient who had NPC with a small tumor confined to the mucosa, the tumor was not detectable on endoscopic examination. Because of a 2-fold increase in plasma EBV DNA on the follow-up analysis, that patient underwent magnetic resonance imaging, which revealed the tumor. Among the participants who did not have NPC but had initially positive plasma EBV DNA results, approximately 66% had negative EBV DNA results after a median of 2 weeks. CONCLUSIONS: Plasma EBV DNA analysis proved useful for detecting early NPC in individuals without a clinical suspicion of NPC. Repeating the test in those who had initially positive results differentiated those with NPC from those who had false-positive results. Cancer 2013. © 2013 American Cancer Society.

Plasma Epstein-Barr Virus DNA and Risk of Future Nasopharyngeal Cancer.

BACKGROUND: We previously conducted a prospective study to show that nasopharyngeal cancer (NPC) screening with circulating Epstein­Barr virus (EBV) DNA analysis can improve survival. However, the long-term significance of positive results in individuals without cancer was unclear. METHODS: We conducted a second-round screening at a median of 43 months after the initial screening. Participants with detectable plasma EBV DNA were retested in 4 weeks, and those with persistently positive results were investigated with nasal endoscopy and magnetic resonance imaging. RESULTS: Of the 20,174 volunteers who participated in the first-round screening, 17,838 (88.6%) were rescreened. Among them, 423 (2.37%) had persistently detectable plasma EBV DNA. Twenty-four patients were identified as having NPC. A significantly higher proportion of patients had stage I/II cancer than in a historical cohort (67% vs. 20%; chi-square test, P<0.001), and they had superior 3-year progression-free survival (100% vs. 78.8%). Compared with participants with undetectable plasma EBV DNA in the first round of screening, participants with transiently and persistently positive results in the first round were more likely to have a cancer identified in the second round, with relative risks of 4.4 (95% confidence interval, 1.3 to 15.0) and 16.8 (95% confidence interval, 5.7 to 49.6), respectively. CONCLUSIONS: Individuals with detectable plasma EBV DNA but without an immediately identifiable NPC were more likely to have the cancer identified in another round of screening performed 3 to 5 years later. (Funded by Kadoorie Charitable Foundation and others; ClinicalTrials.gov number, NCT02063399.)

Recommendations for Epstein-Barr virus-based screening for nasopharyngeal cancer in high- and intermediate-risk regions.

A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.

Primary nasopharyngeal carcinoma: diagnostic accuracy of MR imaging versus that of endoscopy and endoscopic biopsy.

PURPOSE: To compare the accuracy of magnetic resonance (MR) imaging with that of the current clinical standard of endoscopy and endoscopic biopsy, to determine whether MR imaging depicts subclinical cancers missed at endoscopy and endoscopic biopsy, and to determine whether MR imaging can identify patients without nasopharyngeal carcinoma (NPC) who do not need to undergo invasive sampling biopsy. MATERIALS AND METHODS: The study protocol was approved by the institutional review board; written informed consent was obtained from all patients. Patients suspected of having NPC underwent MR imaging, endoscopy, and endoscopic biopsy. Endoscopic biopsy targeted the suspected tumor or sampled the endoscopically normal nasopharynx. The final diagnosis was based on results of the endoscopic biopsy or on results of a repeat biopsy directed at the lesion detected at MR imaging. The sensitivity and specificity of the three investigations were compared by using the Fisher exact test. RESULTS: NPC was present in 77 (31%) of 246 patients and absent in 169 (69%) patients. The combined sensitivity, specificity, and accuracy, respectively, were 100%, 93%, and 95% for MR imaging, 90%, 93%, and 92% for endoscopy, and 95%, 100%, and 98% for endoscopic biopsy. Benign disease was mistaken for NPC in 12 (7%) of 169 patients at MR imaging and in 11 (6%) patients at endoscopy. The sensitivity of MR imaging was significantly higher than that of endoscopy (P = .006) and was similar to that of endoscopic biopsy (P = .120). The specificity of MR imaging was similar to that of endoscopy (P = .120) and was significantly lower than that of endoscopic biopsy (P < .001). CONCLUSION: MR imaging is an accurate test for the diagnosis of NPC. MR imaging depicts subclinical cancers missed at endoscopy and endoscopic biopsy and helps identify the majority of patients who do not have NPC and who therefore do not need to undergo invasive sampling biopsies.

Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape.

Interplay between EBV infection and acquired genetic alterations during nasopharyngeal carcinoma (NPC) development remains vague. Here we report a comprehensive genomic analysis of 70 NPCs, combining whole-genome sequencing (WGS) of microdissected tumor cells with EBV oncogene expression to reveal multiple aspects of cellular-viral co-operation in tumorigenesis. Genomic aberrations along with EBV-encoded LMP1 expression underpin constitutive NF-κB activation in 90% of NPCs. A similar spectrum of somatic aberrations and viral gene expression undermine innate immunity in 79% of cases and adaptive immunity in 47% of cases; mechanisms by which NPC may evade immune surveillance despite its pro-inflammatory phenotype. Additionally, genomic changes impairing TGFBR2 promote oncogenesis and stabilize EBV infection in tumor cells. Fine-mapping of CDKN2A/CDKN2B deletion breakpoints reveals homozygous MTAP deletions in 32-34% of NPCs that confer marked sensitivity to MAT2A inhibition. Our work concludes that NPC is a homogeneously NF-κB-driven and immune-protected, yet potentially druggable, cancer.

Endoscopic assessment of the nasopharynx: an objective score of abnormality to predict the likelihood of malignancy.

OBJECTIVES: We developed an objective endoscopic score of abnormality of the nasopharynx to predict the likelihood of malignancy. METHODS: A score sheet with 44 variables was developed to objectively quantify the bilateral endoscopic assessment of the nasopharynx. Patients scheduled to undergo nasopharyngeal biopsies were recruited. The nasopharynx was assessed endoscopically, photographed, and scored on 44 variables. The scores were compared to the biopsy results, and predictors of malignancy were modeled with regression analysis. The sensitivity and specificity of the novel scoring system were examined. RESULTS: Seventeen patients had carcinoma, and 60 had a benign lesion or no disease. Patients with a nasopharyngeal malignancy scored significantly higher than did patients with a benign lesion or no disease. No patient with a malignant lesion had a score of less than 12. With a receiver operating characteristic curve area of 0.917, the score demonstrated an excellent ability to discriminate between nasopharynges that were likely or unlikely to contain malignant disease. Independent predictors for both malignant disease and a score greater than 12 were modeled. CONCLUSIONS: A cutoff score above 12 on the novel objective endoscopic assessment of the nasopharynx measure was highly predictive of possible malignancy.

Reversal of pale-to-dark nasopharyngeal follicle ratio on narrow-band imaging.

Normal nasopharyngeal mucosa contains varying amounts of lymphoid tissue, which in adults may be minimal or absent. Nasopharyngeal mucosa with minimal lymphoid tissue has a regular follicular pattern on narrow-band imaging; pale follicles have thin, dark borders and the ratio of the pale follicle to the dark border (pale-to-dark ratio) is roughly 90%. In some patients undergoing routine nasopharyngeal endoscopy, the pale-to-dark ratio is reversed on narrow-band imaging, with dark centres surrounded by pale borders and a pale-to-dark ratio of roughly 50%. These dark follicles may represent abnormal capillary loops, as they have the same appearance as microvascular changes seen on narrow-band imaging of the oesophageal mucosa which indicate dysplasia or malignancy. While this observed change in the follicular pattern may be an early event in the evolution of nasopharyngeal carcinoma, the significance of this finding remains to be confirmed by a larger-scale study.

Frontal inverted papillomas: A 25-year study.

OBJECTIVES/HYPOTHESIS: This study analyzes the treatment outcomes of frontal inverted papillomas (FIPs) in an attempt to provide guidelines for surgery selection. STUDY DESIGN: Retrospective case series. METHODS: The treatment results of 29 FIPs classified into five categories were retrospectively analyzed. The five categories are F1, tumor prolapsed into frontal sinus, tumor origin outside frontal sinus; F2, tumor origin inside frontal sinus, medial to the plane of lamina papyracea; F3, tumor origin inside frontal sinus, lateral to the plane of lamina papyracea; F4, bilateral; and F5, extrasinonasal. RESULTS: Of the 11 F1 cases, 73% had Draf I and 27% had Draf IIA procedures. There was one (9%) frontal recurrence and one (9%) frontal stenosis. Of the 10 F2 cases, 10% had Draf I, 40% had Draf IIA, 40% had Draf IIB, and 10% had Draf III surgery with a trephination. One patient (10%) had a frontal recurrence. Of the five F3 cases, 40% had Draf IIA surgery, 20% had external frontoethmoidectomy, and 40% had external frontal sinusotomy. The recurrence rate was 60%, and frontal stenosis rate was 60%. The two F4 cases had external frontal sinusotomies and Draf III surgery with no frontal recurrence or stenosis. The patient with the F5 had a frontal recurrence after Draf IIA surgery and external frontoethmoidectomy. CONCLUSIONS: Draf I or IIA surgery is adequate for most F1 tumors, and Draf II surgery is adequate for most F2 tumors. F3 and F4 tumors can be managed initially by Draf III surgery with external frontal sinusotomy added when required. F5 tumors probably require combined surgical approaches. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:1622-1628, 2020.

Methylation analysis of plasma DNA informs etiologies of Epstein-Barr virus-associated diseases.

Epstein-Barr virus (EBV) is associated with a number of diseases, including malignancies. Currently, it is not known whether patients with different EBV-associated diseases have different methylation profiles of circulating EBV DNA. Through whole-genome methylation analysis of plasma samples from patients with nasopharyngeal carcinoma (NPC), EBV-associated lymphoma and infectious mononucleosis, we demonstrate that EBV DNA methylation profiles exhibit a disease-associated pattern. This observation implies a significant potential for the development of methylation analysis of plasma EBV DNA for NPC diagnostics. We further analyse the plasma EBV DNA methylome of NPC and non-NPC subjects from a prospective screening cohort. Plasma EBV DNA fragments demonstrate differential methylation patterns between NPC and non-NPC subjects. Combining such differential methylation patterns with the fractional concentration (count) and size of plasma EBV DNA, population screening of NPC is performed with an improved positive predictive value of 35.1%, compared to a count- and size-based only protocol.

Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations.

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD, TRAF3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.

Quantitative Epstein-Barr virus DNA analysis and detection of gene promoter hypermethylation in nasopharyngeal (NP) brushing samples from patients with NP carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China and characterized by a strong association with EBV. We aimed to detect EBV DNA and cancer-related gene promoter hypermethylation in nasopharyngeal (NP) brushing samples and provide a novel noninvasive approach for NPC detection. EXPERIMENTAL DESIGN: Twenty-eight NPC cases and 26 noncancerous subjects were prospectively recruited. NP brushing samples were subjected to quantitative real-time PCR analysis of EBV DNA and methylation-specific PCR analysis of the DAP-kinase, RASSF1A, and p16 genes. RESULTS: EBV DNA quantity in NP brushing samples from NPC patients (median, 8.94 copies/actin) was significantly higher than that of controls (median, 0 copies/actin; P < 0.0001). Twenty-seven of 28 NPC patients had detectable EBV DNA in NP brushes, whereas 25 of 26 controls had undetectable or very low levels of EBV DNA. Elevated EBV DNA level in brushing samples as a tumor marker had a sensitivity of 96.4% and a specificity of 96.2% for NPC detection. Moreover, T(1) disease had a significantly lower EBV DNA level as compared with locally more advanced disease (P = 0.037). In brushing samples of NPC patients, the frequencies of DAP-kinase, RASSF1A, and p16 promoter hypermethylation were 50.0%, 39.3%, and 46.4%, respectively. Seventy-eight percent of cases showed methylation of at least one gene. No aberrant hypermethylation was detected in control samples. CONCLUSIONS: Our study demonstrated the feasibility of detecting multiple molecular tumor markers in NP brushing samples with a high sensitivity and specificity for NPC detection. It offers a powerful yet noninvasive approach for the diagnosis of NPC in high-risk populations.

Symptomatic and pathophysiological observations in a modified animal model of allergic rhinitis.

There are many animal models for studying allergic rhinitis. However, they either need a too long establishment period or fail to show significant late allergic responses. In the model described in this paper, guinea pigs were sensitized and challenged intranasally with ovalbumin according to a modified protocol. As controls, antihistamine-treatment and non-sensitized, non-treatment groups were studied in parallel. Early and late symptoms, passive cutaneous anaphylaxis (PCA) reaction, nitric oxide synthase (NOS) immunoreactivities, pathological changes in nasal mucosa and nasal lavage fluid (NLF), and histamine, TXB2 and p-LTs levels in NLF were evaluated. In contrast to the control groups, the model group exhibited typical symptoms, including late phase nasal blockage, and increased levels of IgG1 and IgE. Considerable eosinophil infiltration and eNOS immunoreactivities in nasal mucosa, and increased levels of histamine, TXB2 and p-LTs in NLF were also observed. This model was not only capable of showing satisfactory symptomatic and pathophysiological changes in allergic rhinitis but also showed good responses to antihistamine treatment. The model can be established in six weeks. For the first time, respiratory rate was employed as an index to reflect the nasal blockage of guinea pigs and it proved to be a reliable indicator.

The impact of severe acute respiratory syndrome on otorhinolaryngological services at the Prince of Wales Hospital in Hong Kong.

OBJECTIVES/HYPOTHESIS: The objective was to describe the impact of severe acute respiratory syndrome (SARS) on the services of the division of otorhinolaryngology-head and neck surgery at an academic tertiary referral hospital in Hong Kong. STUDY DESIGN: Descriptive. METHODS: Records of general and subspecialty outpatient attendance, ward admissions, ward bed occupancy, and elective and emergency surgery were obtained for the period since the SARS outbreak and for an equivalent period before the outbreak. The changes in these parameters were determined against the background of new SARS cases. RESULTS: Since the outbreak of SARS in March 2003, the weekly outpatient clinic attendance has declined by 59%, the number of operations performed by 79%, the average ward bed occupancy rate by 79% and the daily admission rate by 84%. A dramatic increase of 300% in the number of patients defaulting on their outpatient appointments was recorded. CONCLUSION: The substantial decrease in otorhinolaryngological services at an academic tertiary referral hospital in Hong Kong has been multifaceted. The decrease in attendance at the outpatient clinics reflects the increased number of patients defaulting on their appointments. Nonessential elective surgery was suspended soon after the outbreak, accounting for the decrease in the number of surgical procedures performed and partially for the decrease in ward bed occupancy and ward admissions. The temporary closure of the accident and emergency department contributed to the decrease in ward admissions and emergency surgical procedures. The reduced service offered by the hospital is having an impact on the quality of care available to patients with non-life-threatening otorhinolaryngological conditions.

A prospective study on the efficacy of mometasone furoate monohydrate aqueous nasal spray on Chinese patients with allergic rhinitis.

OBJECTIVE: We undertook a prospective study of the efficacy of a new intranasal steroid, mometasone furoate nasal spray (Nasonex; Schering-Plough Corp, Kenilworth, NJ). STUDY DESIGN: Chinese patients with allergic rhinitis were recruited. The patients were assessed by a questionnaire that included demographic data and a Rhinitis Symptoms Score. Objective assessments of the nasal passages were performed with a 2.7-mm 30-degree rigid nasoendoscope and scored according to the modified Lund and Kennedy sinusitis staging and scoring for endoscopic appearances of the nasal cavity in rhinosinusitis. Patients were assessed before treatment, and then 200 microg/d MFNS was prescribed. Patients were reevaluated after 8 and 16 weeks of commencement of MFNS. A total of 51 patients completed the 16-week study. RESULTS: There were significant reductions in mean Rhinitis Symptoms Score from 6.19 to 3.8 (P < 0.001) and mean Endoscopic Appearance Score from 4.6 to 3.58 (P = 0.046). Analysis showed that there were reductions in the severity of all 3 aspects of rhinitis symptoms: rhinorrhea, sneezing, and nasal obstruction. CONCLUSION: Mometasone furoate nasal spray was effective in controlling allergic rhinitis and was well tolerated by patients.