John K. S. Woo

Increase in circulating Foxp3+CD4+CD25high regulatory T cells in nasopharyngeal carcinoma patients

Nasopharyngeal carcinoma (NPC) is an Epstein–Barr virus-associated disease with high prevalence in Southern Chinese. Using multiparametric flow cytometry, we identified significant expansions of circulating naïve and memory CD4+CD25high T cells in 56 NPC patients compared with healthy age- and sex-matched controls. These were regulatory T cells (Treg), as they overexpressed Foxp3 and GITR, and demonstrated enhanced suppressive activities against autologous CD4+CD25− T-cell proliferation in functional studies on five patients. Abundant intraepithelial infiltrations of Treg with very high levels of Foxp3 expression and absence of CCR7 expression were also detected in five primary tumours. Our current study is the first to demonstrate an expansion of functional Treg in the circulation of NPC patients and the presence of infiltrating Treg in the tumour microenvironment. As Treg may play an important role in suppressing antitumour immunity, our findings provide critical insights for clinical management of NPC.

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

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.

Management of ingested foreign bodies: a retrospective review of 5240 patients

This review was carried out to assess the effectiveness of our protocol designed for the management of ingested foreign bodies. It was a retrospective review of 5240 patients with ingested foreign bodies admitted over a five-year period to the Ear Nose and Throat Unit. These patients were managed according to a standardized protocol which was adopted and modified from our previous study. Under his management protocol, the mean hospital stay was 1.6 days. Flexible oesophagoscopy under local anaesthesia, and rigid oesophagoscopy under general anaesthesia, were performed in 1.5 per cent and 7.7 per cent of cases respectively. Major complications including oesophageal perforation and deep neck abscesses occurred in 0.19 per cent of patients. There was no mortality. This management protocol for ingested foreign bodies was both safe and cost-effective when compared to similar studies reported in the literature.

Congenital laryngeal cysts: current approach to management

Congenital laryngeal cysts are a rare cause of neonatal upper airway obstruction which may lead to serious morbidity and mortality if diagnosis and treatment are delayed. We reviewed our experience with nine patients over a six-year period. The annual incidence of this condition was 1.82 per 100,000 live births. The diagnosis can be confirmed safely by flexible laryngoscopy before definitive surgery is contemplated. Contrary to other studies, we found that endoscopic removal of cysts can achieve an effective cure without recurrence. Endoscopic deroofing is as effective as endoscopic excision but is technically simpler and thus is recommended as the treatment of choice.

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.

Endoscopic resection of inverted papilloma of the nose and paranasal sinuses

The results of a retrospective study of 22 patients with inverted papillomas resected by the endoscopic approach are presented with a follow-up of 33 to 96 months. Twenty-one patients had unilateral disease and one patient had bilateral involvement. None of the patients had orbital or cranial extension. One patient had synchronous carcinoma in situ. Eight patients had undergone previous surgical procedures. Following endoscopic surgery, six patients had residual disease requiring further revisions. Three of these six patients eventually required excision via limited external approaches. No patient required lateral rhinotomy or mid-facial degloving procedures. No complication occurred in any of the patients. The advantages of endoscopic surgery include precise determination of tumour extent, preservation of normal mucosa and bony structures and avoidance of external scars. Close endoscopic follow-up is mandatory to ensure early recognition and treatment of recurrent disease. Although the endoscopic approach is gaining popularity for the treatment of inverted papilloma, indiscriminate application may result in a high recurrence rate. The endoscopic approach should be performed by experienced surgeons and restricted to carefully selected patients with nasal, ethmoidal and limited maxillary disease. More extensive disease should be managed by radical external approaches or by combining endoscopic with limited external approaches.

A double-blind comparative study of ofloxacin otic drops versus neomycin-polymyxin B-hydrocortisone otic drops in the medical treatment of chronic suppurative otitis media

Active chronic suppurative otitis media poses a management problem when patients are being considered for surgical treatment. Topical antibiotics have demonstrated varying degrees of success in the management of discharging ears. The introduction of quinolones has revived interest in these topical agents. This double-blind study compares two antibiotics, namely ofloxacin and neomycin-polymyxin B, with similar in vitro sensitivities to Gram positive and Gram negative organisms. Fifty-two patients were selected randomly and the results show that ofloxacin eardrops have marginal benefits in symptomatic improvement (89 per cent versus 79 per cent, p = 0.27) and bacterial eradication (81 per cent versus 75 per cent, p = 0.81) in active chronic suppurative otitis media. Significantly fewer patients (seven per cent versus 29 per cent, p = 0.04) in the ofloxacin group had active disease at the end of the two-week treatment. We recommend the use of ofloxacin eardrops in managing active chronic suppurative otitis media since it has high clinical efficacy, contains no steroid component and has no demonstrated risk of ototoxicity.

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 patients 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.)

CD44+ Cancer Stem-Like Cells in EBV-Associated Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs) in the maintenance and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease. Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells. The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1), immune response (CCR7, IL8) and transmembrane transport (e.g. ABCC3, ABCC11) in the spheroids. Among these genes, increased expression of CCR7 in CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphere-forming ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients.

Treatment results of sinonasal inverted papilloma: an 18-year study.

Background This article reviews our treatment results of sinonasal inverted papilloma (SNIP) over the past 18 years. A retrospective observational study was performed. Methods Fifty-six patients with SNIP seen between 1990 and 2008 with follow-up of >2 years were retrospectively analyzed. Results Forty patients (71%) had primary endoscopic resection and 16 patients (29%) had endoscopic-assisted external approaches. Ten patients (18%) had small nasoethmoid residual disease resectable under local anesthesia in the outpatient department. Eight patients (14%) had recurrences requiring revision under general anesthesia, most of which were maxillary and frontal disease requiring additional external approaches. Comparing patients with and without a history of previous surgery (36% versus 64% of all patients), the former had a higher chance of requiring external approaches during the primary resection (45% versus 29%), a higher recurrence rate (45% versus 25%), and a higher chance of external approaches for revision (44% versus 22%). All the first recurrences were at the original tumor site. Eighty-nine percent of the first recurrences were diagnosed within the first 2 years postoperation. Conclusion Thirty-two percent of our patients had recurrence after their primary resection. Recurrences in the nasoethmoid area are usually small and resectable endoscopically under local anesthesia in the outpatient department whereas those inside the maxillary and frontal sinuses are likely to require additional external approaches under general anesthesia. A minimum of 2 years of follow-up is recommended for the preliminary report on the treatment results of this condition. Lifelong follow-up is recommended for possible late recurrences and metachronous multifocal disease.