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"van Hasselt, Andrew C."
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Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer
2017
Circulating Epstein–Barr virus DNA was measured in 20,174 asymptomatic participants in Hong Kong; 34 of 309 with positive results had nasopharyngeal cancer. Stage distribution and progression-free survival were better in the 34 participants than in a historical cohort.
Journal Article
If cytology of Warthin tumor is accurate, can management be conservative?
by
Vlantis, Alexander C
,
Ng, Siu Kwan
,
Mak, Chi Keung
in
Adenocarcinoma - diagnosis
,
Adenocarcinoma - pathology
,
Adenolymphoma
2016
We conducted a retrospective study to assess the accuracy of fine-needle aspiration cytology (FNAC) in the diagnosis of Warthin tumor and to evaluate the subsequent risk of conservative nonsurgical management. We reviewed the records of 75 patients (76 tumors) with a parotid mass that had been diagnosed as a Warthin tumor by FNAC. This patient population was made up of 64 men and 11 women, aged 46 to 93 years (mean: 67). Of the 76 tumors, 40 were treated with surgical excision and 36 with conservative measures. Histology of the 40 excised parotid masses revealed that 38 (95%) were indeed Warthin tumors, 1 (2.5%) was a low-grade adenocarcinoma, and 1 was benign-not otherwise specified. None of the 36 tumors underwent malignant transformation either clinically or on repeat FNAC (if performed) during a follow-up of 4 to 120 months (mean: 55.5 ± 32.2). We conclude that conservative management of Warthin tumors confidently diagnosed on FNAC may be an option for patients who are unwilling or unable to undergo surgical excision.
Journal Article
Whole-genome profiling of nasopharyngeal carcinoma reveals viral-host co-operation in inflammatory NF-κB activation and immune escape
2021
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.
The genomic characterisation of nasopharyngeal carcinoma (NPC) remains crucial. Here, the authors perform whole-genome sequencing for 70 NPCs with EBV gene expression, report the somatic alterations and EBV-mediated effects converging on NF-κB activation and immune escape and identify targetable homozygous MTAP deletions.
Journal Article
Exome and genome sequencing of nasopharynx cancer identifies NF-kappaB pathway activating mutations
2017
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.
Journal Article
Conservative Management of Postoperative Chylous Fistula with Octreotide and Peripheral Total Parenteral Nutrition
by
Wong, Eddy W.Y.
,
Chan, Jason Y.K.
,
van Hasselt, C. Andrew
in
Care and treatment
,
Chyle
,
Chylothorax - etiology
2017
Postoperative chylous fistula after neck dissection is an uncommon complication associated with significant patient morbidity. Octreotide acetate is a somatostatin analogue established in the treatment of chylothorax; however, its utility in the management of cervical chylous fistulae has not been fully evaluated. The investigators hypothesized that chylous fistula can be managed by a combination of octreotide and peripheral total parenteral nutrition (TPN). A retrospective review of cases compiled at our institution from 2009 to 2015 was conducted. Ten patients, all men, were identified as having a postoperative chylous fistula after a neck dissection. All patients were treated with peripheral TPN and intravenous octreotide. Mean age of the patients was 63.0 years (range 49 to 82). Five (50.0%) had a neck dissection for the management of metastatic nasopharyngeal carcinoma and had previous neck irradiation. In 8 (80%) patients, chylous fistula occurred in the left neck. Seven (70.0%) of the leaks occurred within the first 2 postoperative days. Eight (80%) leaks were controlled using TPN and octreotide, with 2 (20%) patients requiring surgical intervention. No factors were significant in the successful conservative management of chylous fistulae. One patient with a chylous fistula of 1,800 ml/day was managed successfully without surgical intervention. The results of this case series suggest that chylous fistulae may be managed conservatively with octreotide and TPN. However, long-term evaluation is needed to define if and when surgical intervention is required for control.
Journal Article
Otitis Media with Effusion and Hearing Loss in Chinese Children with Cleft Lip and Palate
by
Kwan, Wendy M.Y.
,
Van Hasselt, C. Andrew
,
Tong, Michael C.F.
in
Asian people
,
Bacterial diseases
,
Biological and medical sciences
2011
Objective
To determine the incidence of otitis media with effusion and the associated hearing loss, the rate of ventilation tube insertion, and complications of ventilation tube insertion in Chinese cleft palate patients.
Design
Retrospective review in a tertiary care hospital in Hong Kong.
Patients
A total of 104 consecutive patients with cleft lip and/or cleft palate who were born between January 1996 and January 2006.
Results
The incidence of otitis media with effusion in Chinese cleft palate patients for the first 2 years after birth was 76.1%. Of these patients, 16.9% had otitis media with effusion associated with a moderate hearing loss (40 decibels hearing level [dBHL]). Approximately half (53.2%) of our patients had ventilation tube insertion. Complications including retraction, tympanosclerosis, and perforation of the tympanic membrane were found in 15.7% of all ears with otitis media with effusion and ventilation tube insertion.
Conclusions
The high incidence of otitis media with effusion in cleft palate infants found in this study is consistent with that reported in the Western literature. A small but significant proportion of otitis media with effusion was associated with moderate hearing loss that truly required surgical treatment. Cleft palate children are much more likely to develop otitis media with effusion than normal children, and they develop the condition at an earlier age. A protocol for the treatment of otitis media with effusion in cleft palate patients and further prospective studies are warranted.
Journal Article
A Case-Control Study of the Risk Factors Associated with Sinonasal Inverted Papilloma
by
Lee, Dennis L.Y.
,
van Hasselt, C. Andrew
,
Tong, Michael C.F.
in
Adult
,
Aged
,
Aged, 80 and over
2010
The etiology of sinonasal inverted papilloma (IP) is unknown. This study was designed to evaluate the possible risk factors associated with IP Methods: This is a case-control epidemiology study in a tertiary referral center. Fifty patients with IP and 150 matched controls were interviewed using a questionnaire on suspected risk factors. Univariate analysis of the risk factors and calculation of the matched odds ratios, the corresponding 95% CIs, and p values was performed. Significant risk factors were further studied using conditional logistic regression analysis.
Outdoor and industrial occupations were associated with IP. Tobacco smoking, drinking alcohol, history of allergic rhinitis, sinusitis, nasal polyp, non-sinonasal papilloma and non-sinonasal malignancy were not significant factors.
Outdoor and industrial occupations were associated with IP and may be potential risk factors. Future studies are warranted to further evaluate the individual type of occupation and chemical involved.
Journal Article
Treatment Results of Sinonasal Inverted Papilloma: An 18-Year Study
2009
This article reviews our treatment results of sinonasal inverted papilloma (SNIP) over the past 18 years. A retrospective observational study was performed.
Fifty-six patients with SNIP seen between 1990 and 2008 with follow-up of >2 years were retrospectively analyzed.
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.
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.
Journal Article
An Application of Item Response Theory and the Rasch Model in Speech Recognition Test Materials
by
Lam, Joffee H. S.
,
van Hasselt, C. Andrew
,
Tong, Michael C. F.
in
Acknowledgment
,
Adolescent
,
Cantonese
2016
The purpose of this study was to describe an attempt to apply item-response theory (IRT) and the Rasch model to construction of speech-recognition tests. A set of word-recognition test items applicable to children as young as 3 years old-with any level of hearing sensitivity, with or without using hearing devices-was developed.
Test items were constructed through expert consultation and by reference to some established language corpora, validated with 121 participants with various degrees of hearing loss and 255 with typical hearing. IRT and the Rasch model were applied to evaluate item quality.
Eighty disyllabic word items were selected in accordance with IRT. The speech-recognition abilities of the 376 young participants are reported. The IRT analyses on this set of data are also discussed.
A new set of speech-recognition test materials in Cantonese Chinese has been developed. Construction of short equivalent lists may be performed in accordance with IRT item qualities. Clinical applications of this test tool in the particular language population are discussed.
Journal Article
Peri-operative hyperglycemia: a consideration for general surgery?
by
Lee, Ping Yin
,
Underwood, Malcolm J.
,
Jiang, Johnny Y.
in
Adrenal glands
,
Adult
,
Age composition
2010
Intraoperative hyperglycemia in cardiac and neurosurgical patients is significantly associated with morbidity. Little is known about the perioperative glycemic profile or its impact in other surgical populations or in nondiabetic patients.
A systematic review of blood glucose values during major general surgical procedures reported since 1980 was conducted. Data extracted included blood glucose measures, study sample size, gender distribution, age grouping, study purpose, surgical procedure, anesthetic details, and infusion regime. Excluded studies were those with subjects with diabetes insipidus, insulin-treated diabetes, renal or hepatic failure, adrenal gland tumors or dysfunction, pregnancy, and emergency or trauma surgery.
Blood glucose levels rose significantly with the induction of anesthesia (
P < .001) in nondiabetic patients. At incision, 2 hours, 4 hours, and 6 hours, 30%, 40%, 38%, and 40% of studies, respectively, reported hyperglycemia.
Factors that confound or protect against significant rises in perioperative glycemic levels in nondiabetic patients were identified. The findings facilitate investigating the impact of hyperglycemia on general surgical outcomes.
Journal Article