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Background: Over-expression of cyclooxygenase-2 (COX-2) enzyme has been reported in nasopharyngeal carcinoma (NPC). However, the prognostic significance of this has yet to be conclusively determined. Thus, from our randomized trial of radiation versus concurrent chemoradiation in endemic NPC, we analyzed a cohort of tumour samples collected from participants from one referral hospital.Methods: 58 out of 88 patients from this institution had samples available for analysis. COX-2 expression levels were stratified by immunohistochemistry, into negligible, weak, moderate and strong, and correlated with overall and disease specific survivals.Results: 58% had negligible or weak COX-2 expression, while 14% and 28% had moderate and strong expression respectively. Weak COX-2 expression conferred a poorer median overall survival, 1.3 years for weak versus 6.3 years for negligible, 7.8 years, strong and not reached for moderate. There was a similar trend for disease specific survival.Conclusion: Contrary to literature published on other malignancies, our findings seemed to indicate that over-expression of COX-2 confer a better prognosis in patients with endemic NPC. Larger studies are required to conclusively determine the significance of COX-2 expression in these patients. [ABSTRACT FROM AUTHOR]

The effects of the COVID-19 pandemic continue to constrain health-care staff and resources worldwide, despite the availability of effective vaccines. Aerosol-generating procedures such as endoscopy, a common investigation tool for nasopharyngeal carcinoma, are recognised as a likely cause of SARS-CoV-2 spread in hospitals. Plasma Epstein-Barr virus (EBV) DNA is considered the most accurate biomarker for the routine management of nasopharyngeal carcinoma. A consensus statement on whether plasma EBV DNA can minimise the need for or replace aerosol-generating procedures, imaging methods, and face-to-face consultations in managing nasopharyngeal carcinoma is urgently needed amid the current pandemic and potentially for future highly contagious airborne diseases or natural disasters. We completed a modified Delphi consensus process of three rounds with 33 international experts in otorhinolaryngology or head and neck surgery, radiation oncology, medical oncology, and clinical oncology with vast experience in managing nasopharyngeal carcinoma, representing 51 international professional societies and national clinical trial groups. These consensus recommendations aim to enhance consistency in clinical practice, reduce ambiguity in delivering care, and offer advice for clinicians worldwide who work in endemic and non-endemic regions of nasopharyngeal carcinoma, in the context of COVID-19 and other airborne pandemics, and in future unexpected settings of severe resource constraints and insufficiency of personal protective equipment., Competing Interests: Declaration of interests VH-FL reports personal fees and grants from AstraZeneca; and personal fees from AQUILAB, Amgen, Boston Scientific, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, and Takeda, all outside this Policy Review. GFH reports fees paid to the institution from Eli Lilly, Regeneron, Merck Sharp and Dohme, AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, and Pfizer; and personal fees from Merck Sharp and Dohme, Novartis, Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, Ipsen, Bristol Myers Squibb, Janssen, and Taiho, all outside the scope of this Policy Review. WKJL is a shareholder of Illumina/GRAIL. Q-TL reports personal fees from the RTOG Foundation and NRG Oncology, outside the scope of this Policy Review, and is supported by the US National Institutes of Health (2U10CA180868-06, 1R01DE029672-01A1, P30CA124435, and R01DE030894-01A1). NYL is supported by the US National Institutes of Health (R01 CA238392-02A1 and 5UG1CA233290-02). DW-TL reports institutional fees from Bristol Myers Squibb, Merck Sharp and Dohme, Boehringer Ingelheim, Janssen, and Novartis, outside the scope of this Policy Review. RM reports personal fees from Merck Pharmaceuticals, Merck Sharp and Dohme, Bristol Myers Squibb, Roche, Amgen, AstraZeneca, Nanobiotix, Seattle Genetics, and Boehringer Ingelheim, all outside the scope of this Policy Review. RK-CN reports personal fees from Pfizer, Novartis, Sanofi, AstraZeneca, Eli Lilly, Merck Sharp and Dohme, Zai Lab, Roche, Eisai, Merck Pharmaceutical, Astellas, and Nuance (China), outside the scope of this Policy Review. RK-YT is the President of Hong Kong Society of Otolaryngology, Head and Neck Surgery, and past President of Hong Kong Head and Neck Society. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Reirradiation for locally recurrent nasopharyngeal carcinoma (NPC) is challenging because prior radiation dose delivered in the first course is often close to the tolerance limit of surrounding normal structures. A delicate balance between achieving local salvage and minimizing treatment toxicities is needed. However, high-level evidence is lacking because available reports are mostly retrospective studies on small series of patients. Pragmatic consensus guidelines, based on an extensive literature search and the pooling of opinions by leading specialists, will provide a useful reference to assist decision-making for these difficult decisions., Methods and Materials: A thorough review of available literature on recurrent NPC was conducted. A set of questions and preliminary draft guideline was circulated to a panel of international specialists with extensive experience in this field for voting on controversial areas and comments. A refined second proposal, based on a summary of the initial voting and different opinions expressed, was recirculated to the whole panel for review and reconsideration. The current guideline was based on majority voting after repeated iteration for final agreement., Results: The initial round of questions showed variations in clinical practice even among the specialists, reflecting the lack of high-quality supporting data and the difficulties in formulating clinical decisions. Through exchange of comments and iterative revisions, recommendations with high-to-moderate agreement were formulated on general treatment strategies and details of reirradiation (including patient selection, targets contouring, dose prescription, and constraints)., Conclusion: This paper provides useful reference on radical salvage treatment strategies for recurrent NPC and optimization of reirradiation through review of published evidence and consensus building. However, the final decision by the attending clinician must include full consideration of an individual patient's condition, understanding of the delicate balance between risk and benefits, and acceptance of risk of complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The treatment of nasopharyngeal carcinoma requires high radiation doses. The balance of the risks of local recurrence owing to inadequate tumor coverage versus the potential damage to the adjacent organs at risk (OARs) is of critical importance. With advancements in technology, high target conformality is possible. Nonetheless, to achieve the best possible dose distribution, optimal setting of dose targets and dose prioritization for tumor volumes and various OARs is fundamental. Radiation doses should always be guided by the As Low As Reasonably Practicable principle. There are marked variations in practice. This study aimed to develop a guideline to serve as a global practical reference., Methods and Materials: A literature search on dose tolerances and normal-tissue complications after treatment for nasopharyngeal carcinoma was conducted. In addition, published guidelines and protocols on dose prioritization and constraints were reviewed. A text document and preliminary set of variants was circulated to a panel of international experts with publications or extensive experience in the field. An anonymized voting process was conducted to rank the proposed variants. A summary of the initial voting and different opinions expressed by members were then recirculated to the whole panel for review and reconsideration. Based on the comments of the panel, a refined second proposal was recirculated to the same panel. The current guideline was based on majority voting after repeated iteration for final agreement., Results: Variation in opinion among international experts was repeatedly iterated to develop a guideline describing appropriate dose prioritization and constraints. The percentage of final agreement on the recommended parameters and alternative views is shown. The rationale for the recommendations and the limitations of current evidence are discussed., Conclusions: Through this comprehensive review of available evidence and interactive exchange of vast experience by international experts, a guideline was developed to provide a practical reference for setting dose prioritization and acceptance criteria for tumor volumes and OARs. The final decision on the treatment prescription should be based on the individual clinical situation and the patient's acceptance of optimal balance of risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Radiomics pipelines have been developed to extract novel information from radiological images, which may help in phenotypic profiling of tumours that would correlate to prognosis. Here, we compared two publicly available pipelines for radiomics analyses on head and neck CT and MRI in nasopharynx cancer (NPC)., Methods and Materials: 100 biopsy-proven NPC cases stratified by T- and N-categories were enrolled in this study. Two radiomics pipeline, Moddicom (v. 0.51) and Pyradiomics (v. 2.1.2) were used to extract radiomics features of CT and MRI. Segmentation of primary gross tumour volume was performed using Velocity v. 4.0 by consensus agreement between three radiation oncologists. Intraclass correlation between common features of the two pipelines was analysed by Spearman's rank correlation. Unsupervised hierarchical clustering was used to determine association between radiomics features and clinical parameters., Results: We observed a high proportion of correlated features in the CT data set, but not for MRI; 76.1% (51 of 67 common between Moddicom and Pyradiomics) of CT features and 28.6% (20 of 70 common) of MRI features were significantly correlated. Of these, 100% were shape-related for both CT and MRI, 100 and 23.5% were first-order-related, 61.9 and 19.0% were texture-related, respectively. This interpipeline heterogeneity affected the downstream clustering with known prognostic clinical parameters of cTN-status and GTVp. Nonetheless, shape features were the most reproducible predictors of clinical parameters among the different radiomics modules., Conclusion: Here, we highlighted significant heterogeneity between two publicly available radiomics pipelines that could affect the downstream association with prognostic clinical factors in NPC., Advances in Knowledge: The present study emphasized the broader importance of selecting stable radiomics features for disease phenotyping, and it is necessary prior to any investigation of multicentre imaging datasets to validate the stability of CT-related radiomics features for clinical prognostication.

Purpose: Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome., Method: A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies., Results: Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration., Conclusion: Through this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients' factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with International Union Against Cancer (UICC)-staged III/IVA,B nasopharyngeal carcinoma (NPC), who were enrolled into two randomised controlled trials of concurrent/adjuvant chemotherapy when added to radiotherapy (SQNP01), and induction chemotherapy when added to chemoradiotherapy (NCC0901)., Material and Methods: A post hoc analysis of pooled cohorts from SQNP01 (N = 221) and NCC0901 (N = 172) was performed. We employed a threshold of pre-treatment NLR = 3.0 (median) to stratify patients. Survival outcomes were compared using log-rank test. Multivariable Cox regression analyses were performed to assess association between NLR and overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS)., Results: High NLR (≥3.0) was associated with advanced T-status (p = 0.002), N-status (p = 0.002), overall UICC stage (p = 0.004), and high pre-treatment Epstein-Barr virus DNA titre (p = 0.001). High NLR was not associated with OS (0.94 [0.67-1.32], p = 0.7), DFS (0.98 [0.73-1.33], p = 0.9), DMFS (1.02 [0.66-1.57], p = 0.9), and LRFS (1.37 [0.84-2.22], p = 0.2) on univariable and multivariable analyses, while conventional clinical indices (T-status, N-status, and overall UICC stage) were prognostic of clinical outcomes. High NLR also did not predict for a treatment effect with the experimental arms in both trials., Conclusion: Our pooled analyses that were confined to a homogenous patient population of locally advanced NPC do not suggest that NLR adds prognostic value to conventional clinical indices in identifying patients with unfavourable disease., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The appearance of people associated with the Lapita culture in the South Pacific around 3,000 years ago marked the beginning of the last major human dispersal to unpopulated lands. However, the relationship of these pioneers to the long-established Papuan people of the New Guinea region is unclear. Here we present genome-wide ancient DNA data from three individuals from Vanuatu (about 3,100-2,700 years before present) and one from Tonga (about 2,700-2,300 years before present), and analyse them with data from 778 present-day East Asians and Oceanians. Today, indigenous people of the South Pacific harbour a mixture of ancestry from Papuans and a population of East Asian origin that no longer exists in unmixed form, but is a match to the ancient individuals. Most analyses have interpreted the minimum of twenty-five per cent Papuan ancestry in the region today as evidence that the first humans to reach Remote Oceania, including Polynesia, were derived from population mixtures near New Guinea, before their further expansion into Remote Oceania. However, our finding that the ancient individuals had little to no Papuan ancestry implies that later human population movements spread Papuan ancestry through the South Pacific after the first peopling of the islands.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

Background: The current World Health Organization (WHO) classification of nasopharyngeal carcinoma (NPC) conveys little prognostic information. This study aimed to propose an NPC histopathologic classification that can potentially be used to predict prognosis and treatment response., Methods: We initially developed a histopathologic classification based on the morphologic traits and cell differentiation of tumors of 2716 NPC patients who were identified at Sun Yat-sen University Cancer Center (SYSUCC) (training cohort). Then, the proposed classification was applied to 1702 patients (retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients (prospective validation cohort) from SYSUCC. The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes. We used Cox proportional hazards models to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS)., Results: The 5-year OS rates for all NPC patients who were diagnosed with epithelial carcinoma (EC; 3708 patients), mixed sarcomatoid-epithelial carcinoma (MSEC; 1247 patients), sarcomatoid carcinoma (SC; 823 patients), and squamous cell carcinoma (SCC; 253 patients) were 79.4%, 70.5%, 59.6%, and 42.6%, respectively (P < 0.001). In multivariate models, patients with MSEC had a shorter OS than patients with EC (HR = 1.44, 95% CI = 1.27-1.62), SC (HR = 2.00, 95% CI = 1.76-2.28), or SCC (HR = 4.23, 95% CI = 3.34-5.38). Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC (HR = 0.67, 95% CI = 0.56-0.80), MSEC (HR = 0.58, 95% CI = 0.49-0.75), and possibly for those with SCC (HR = 0.63; 95% CI = 0.40-0.98), but not for patients with SC (HR = 0.97, 95% CI = 0.74-1.28)., Conclusions: The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associated with a poor prognosis.

Current proposed mechanisms implicate both early and latent Epstein-Barr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early childhood EBV infection and with chronic ear, nose, and sinus conditions. Moreover, most patients with NPC present with IgA antibody titers to EBV capsid antigen (VCA-IgA), which can precede actual tumor presentation by several years. If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis, one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection. It is perhaps possible that EBV resides within the salivary glands, instead of the epithelium, during latency. This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased susceptibility to NPC and immature salivary gland morphogenesis, the latter of which is influenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene (EDAR), EDARV370A. Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain, but in patients with infectious mononucleosis, EBV has been isolated in this anatomical organ. The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus. Adding to the fact that the fossa of Rosen Müller contains a transformative zone active only in the first decade of life, one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.

In order to explore the diversity and selective signatures of duplication and deletion human copy-number variants (CNVs), we sequenced 236 individuals from 125 distinct human populations. We observed that duplications exhibit fundamentally different population genetic and selective signatures than deletions and are more likely to be stratified between human populations. Through reconstruction of the ancestral human genome, we identify megabases of DNA lost in different human lineages and pinpoint large duplications that introgressed from the extinct Denisova lineage now found at high frequency exclusively in Oceanic populations. We find that the proportion of CNV base pairs to single-nucleotide-variant base pairs is greater among non-Africans than it is among African populations, but we conclude that this difference is likely due to unique aspects of non-African population history as opposed to differences in CNV load., (Copyright © 2015, American Association for the Advancement of Science.)

Background and Purpose: To recommend contouring methods and atlas of organs at risk (OARs) for nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy, in order to help reach a consensus on interpretations of OARs delineation., Methods and Materials: Two to four contouring methods for the middle ear, inner ear, temporal lobe, parotid gland and spinal cord were identified via systematic literature review; their volumes and dosimetric parameters were compared in 41 patients. Areas under the receiver operating characteristic curves for temporal lobe contouring were compared in 21 patients with unilateral temporal lobe necrosis (TLN)., Results: Various contouring methods for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord lead to different volumes and dosimetric parameters (P<0.05). For TLN, D1 of PRV was the most relevant dosimetric parameter and 64Gy was the critical point. We suggest contouring for the temporal lobe, middle ear, inner ear, parotid gland and spinal cord. A CT-MRI fusion atlas comprising 33 OARs was developed., Conclusions: Different dosimetric parameters may hinder the dosimetric research. The present recommendation and atlas, may help reach a consensus on subjective interpretation of OARs delineation to reduce inter-institutional differences in NPC patients., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Purpose: We sought to evaluate the nature and frequency of late toxicities in a cohort of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy alone., Methods and Materials: Seven-hundred and ninety-six consecutive NPC patients treated using conventional radiotherapy at a single center from 1992 to 1995 were retrospectively analyzed. Patients with histology proven, completely staged, Stage I-IVB World Health Organization Type I-III NPC and completed radical radiotherapy were included. Patients with incomplete staging investigations, distant metastases at diagnosis, previous treatment, and incomplete radiotherapy were excluded. Radiotherapy-related complications were categorized using the RTOG Late Radiation Morbidity Scoring Criteria., Results: Median follow-up was 7.2 years. The 5-year overall survival and disease free survival were 69% and 56%, respectively, and the corresponding 10-year rates were 52% and 44%. Among 771 patients with at least 3 months of follow-up post treatment, 565 (73%) developed RT-related complications. Diagnosed neurological complications were cranial nerve palsies (n=70; 9%), temporal lobe necrosis (n=37; 5%), Lhermitte's syndrome (n=7; 1%), and brachial plexopathy (n=2; 0.3%). Non-neurological complications included xerostomia (n=353; 46%), neck fibrosis (n=169; 22%), hypo-pituitarism (n=48; 6%), hearing loss (n=120; 16%), dysphagia (n=116; 15%), otorrhea (n=101; 13%), tinnitus (n=94; 12%), permanent tube feeding (n=61; 8%), trismus (n=45; 6%), second malignancies within treatment field (n=17; 2%), and osteo-radionecrosis (n=13; 2%)., Conclusions: While radiotherapy is curative in NPC, many patients suffer significant late treatment morbidities with conventional radiotherapy techniques., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Currently, nasopharyngeal carcinoma (NPC) prognosis evaluation is based primarily on the TNM staging system. This study aims to identify prognostic markers for NPC., Patients and Methods: We detected expression of 18 biomarkers by immunohistochemistry in NPC tumors from 209 patients and evaluated the association between gene expression level and disease-specific survival (DSS). We used support vector machine (SVM)--based methods to develop a prognostic classifier for NPC (NPC-SVM classifier). Further validation of the NPC-SVM classifier was performed in an independent cohort of 1,059 patients., Results: The NPC-SVM classifier integrated patient sex and the protein expression level of seven genes, including Epstein-Barr virus latency membrane protein 1, CD147, caveolin-1, phospho-P70S6 kinase, matrix metalloproteinase 11, survivin, and secreted protein acidic and rich in cysteine. The NPC-SVM classifier distinguished patients with NPC into low- and high-risk groups with significant differences in 5-year DSS in the evaluated patients (87% v 37.7%; P < .001) in the validation cohort. In multivariate analysis adjusted for age, TNM stage, and histologic subtype, the NPC-SVM classifier was an independent predictor of 5-year DSS in the evaluated patients (hazard ratio, 4.9; 95% CI, 3.0 to 7.9) in the validation cohort., Conclusion: As a powerful predictor of 5-year DSS among patients with NPC, the newly developed NPC-SVM classifier based on tumor-associated biomarkers will facilitate patient counseling and individualize management of patients with NPC.

Introduction: This is a retrospective study aimed to analyse the outcomes of oral tongue cancer with emphasis on young people., Materials and Methods: Patients treated radically between 1998 and 2006 were included and categorised according to treatment modalities (Group A: Surgery, Group B: Surgery and adjuvant therapy, Group C: Definitive radiotherapy) and age groups (≤ 40 and > 40 years). Overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRS) and metastasis-free survival (MFS) were estimated using Kaplan-Meier method., Results: There were 123 patients with 32%, 53% and 15% in Group A, B and C, respectively. Of these, 17 patients (14%) were ≤40 years with 6 (15%), 8 (12%) and 3 (16%) young oral tongues in Group A, B and C, respectively. Five-year OS and DFS were 69%/72%, 41%/47% and 16%/9.5% for Group A, B and C, respectively. Young patients had similar survival as the older population with 5-year OS of 83%, 75% and 33% in Group A, B and C, as compared to the older patients (66%, 36% and 13%, respectively)., Conclusion: Young oral tongue patients did not have worse outcomes.

Nasopharyngeal cancer (NPC) is endemic in Southern China, with Guandong province and Hong Kong reporting some of the highest incidences in the world. The journal Science has called it a "Cantonese cancer". We propose that in fact NPC is a cancer that originated in the Bai Yue ("proto Tai Kadai" or "proto Austronesian" or "proto Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage. However, the work by John Ho raised the profile of NPC, and because of the high incidence of NPC in Hong Kong and Guangzhou, NPC became known as a Cantonese cancer. We searched historical articles, articles cited in PubMed, Google, monographs, books and Internet articles relating to genetics of the peoples with high populations of NPC. The migration history of these various peoples was extensively researched, and where possible, their genetic fingerprint identified to corroborate with historical accounts. Genetic and anthropological evidence suggest there are a lot of similarities between the Bai Yue and the aboriginal peoples of Borneo and Northeast India; between Inuit of Greenland, Austronesian Mayalo Polynesians of Southeast Asia and Polynesians of Oceania, suggesting some common ancestry. Genetic studies also suggest the present Cantonese, Minnans and Hakkas are probably an admixture of northern Han and southern Bai Yue. All these populations have a high incidence of NPC. Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.

The addition of a planned neck dissection after radiotherapy has traditionally been considered standard of care for patients with positive neck-nodal disease. With the acceptance of chemoradiotherapy as the new primary treatment for patients with locally advanced squamous-cell head and neck cancers, and the increasing numbers of patients who achieve a complete response, the role of planned neck dissection is now being questioned. The accuracy and availability of a physical examination or of different imaging modalities to identify true complete responses adds controversy to this issue. This consensus statement will address some of the controversies surrounding the role of neck dissection following chemoradiotherapy for squamous-cell carcinomas of the head and neck, with particular reference to patients in Asia.

Introduction: Human Vgamma2Vdelta2 T cells play important role in immunity to infection and cancer by monitoring self and foreign isoprenoid metabolites with their gammadelta T cell antigen receptors. Like CD4 and CD8 alphabeta T cells, adult peripheral Vgamma2Vdelta2 T cells represent a pool of heterogeneous cells with distinct functional capabilities., Purpose: The aim of this study was to characterize the phenotypes and functions of various Vgamma2Vdelta2 T cell subsets in patients with nasopharyngeal carcinoma (NPC). We sought to develop a better understanding of the role of these cells during the course of disease and to facilitate the development of immunotherapeutic strategies against NPC., Results: Although similar total percentages of peripheral blood Vgamma2Vdelta2 T cells were found in both NPC patients and normal donors, Vgamma2Vdelta2 T cells from NPC patients showed decreased cytotoxicity against tumor cells whereas Vgamma2Vdelta2 T cells from normal donors showed potent cytotoxicity. To investigate further, we compared the phenotypic characteristics of Vgamma2Vdelta2 T cells from 96 patients with NPC and 54 healthy controls. The fraction of late effector memory Vgamma2Vdelta2 T cells (T(EM RA)) was significantly increased in NPC patients with corresponding decreases in the fraction of early memory Vgamma2Vdelta2 T cells (T(CM)) compared with those in healthy controls. Moreover, T(EM RA) and T(CM) Vgamma2Vdelta2 cells from NPC patients produced significantly less IFN-gamma and TNF-alpha, potentially contributing to their impaired cytotoxicity. Radiotherapy or concurrent chemo-radiotherapy further increased the T(EM RA) Vgamma2Vdelta2 T cell population but did not correct the impaired production of IFN-gamma and TNF-alpha observed for T(EM RA) Vgamma2Vdelta2 T cells., Conclusion: We have identified distinct alterations in the Vgamma2Vdelta2 T cell subsets of patients with NPC. Moreover, the overall cellular effector function of gammadelta T cells is compromised in these patients. Our data suggest that the contribution of Vgamma2Vdelta2 T cells to control NPC may depend on the activation state and differentiation of these cells.

Background: Endemic nasopharyngeal carcinoma (NPC) commonly metastasizes to the lungs, liver, and bones. This study aims to assess the efficacy of 4 distant metastasis staging modalities, namely (1) conventional work-up comprising chest X-ray, liver ultrasound, and skeletal scintigraphy, (2) CT of the thorax, abdomen, and skeletal scintigraphy, (3) (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), and (4) integrated FDG-PET/CT., Methods: Seventy-eight consecutive patients diagnosed with NPC were enrolled and followed up for a minimum of 6 months to confirm the staging at diagnosis., Results: Six patients (7.7%) had distant metastases at diagnosis. The sensitivities and specificities of conventional work-up, combined CT and skeletal scintigraphy, FDG-PET, and FDG-PET/CT were 33.3%, 66.7%, 83.3%, and 83.3%; and 90.3%, 91.7%, 94.4%, and 97.2%, respectively. The corresponding accuracies were 85.9%, 89.7%, 93.6%, and 96.2%., Conclusions: FDG-PET/CT is the most sensitive, specific, and accurate modality for distant metastasis staging of endemic NPC.

Background: We sought to assess the efficacy and complications of linear accelerator-based stereotactic radiosurgery (SRS) plus intracavitary irradiation (ICI) as salvage treatment for local persistent and recurrent nasopharyngeal carcinoma (NPC) after primary external beam radiotherapy (EBRT)., Methods: Between July 1995 and June 2003, 36 patients (25 men and 11 women; median age, 48 years; range, 22-66 years) with local recurrent NPC confined to the nasopharynx (rT1) or limited extension to the parapharynx and nasal cavity (rT2) were treated with SRS plus ICI. Nineteen patients had rT1 and 17 had rT2 disease. Five patients (13.8%) had persistent disease, and 31 patients (86.1%) had recurrent disease using the definition of >4 months after the primary treatment as recurrent relapse. The median target volume was 36.3 cm(3) (range, 10.3-56.2 cm(3)) for the SRS treatment. All patients received 18 Gy to the 90% isodose line followed by two separate ICI 6 Gy each to 0.5 cm from the surface of the endotracheal balloon. Patients were assessed with serial nasoendoscopy and repeat scans (CT or MRI) at 3 months, and suspicious lesions were rebiopsied., Results: The median follow-up for surviving patients was 4.24 years (range, 0.73-8.81 years). Twenty-two of 36 (61%) patients were alive at the time of reporting. Twenty patients were free of disease, and two patients were alive with disease. Fourteen of 36 (39%) patients had died (five of distant metastases, six of local recurrences, two of both local disease and distant metastases, and one of unrelated cause). Patients with rT1 disease (median survival not reached) fared better that patients with rT2 disease (median survival, 4.6 years). The actuarial 5-year disease-free survival and overall survival (OS) were 57% (rT1 78%, rT2 39%) and 62% (rT1 80%, rT2 48%), respectively. The actuarial 5-year local control was 65% (rT1 82%, rT2 49%). The treatment was well tolerated with no significant acute complications. Sixteen patients (44%) had late complications, including palatal fibrosis in six patients (17%), trismus in seven patients (20%), cranial nerve palsies in seven patients (20%), temporal lobe necrosis in two patients (8%), and osteoradionecrosis of the skull base in six patients (17%). The complication-free survival rates at 2 and 5 years were 70% (95% confidence interval [CI], 56% to 87%) and 31% (95% CI, 17% to 56%), respectively. No patient died as a direct result of the late complication., Conclusion: Although our series is small, the combination of SRS and ICI seems to be an effective salvage treatment for early-stage recurrent NPC. The OS of 62% at 5 years is very encouraging and favorable compared with reported reirradiation or surgical series. The late complications are considerable but expected because of the high doses of radiation previously delivered. The ideal dose fractionation for SRS and ICI is unknown and remains to be defined., (Copyright 2005 Wiley Periodicals, Inc.)

Background: We conducted two parallel phase II trials in chemonaïve and previously treated patients with metastatic nasopharyngeal carcinoma (NPC) to evaluate the tumour response, progression-free and overall survival, and toxicity of gemcitabine., Patients and Methods: Gemcitabine 1250 mg/m2 was given on days 1 and 8 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status <2, adequate renal, hepatic and bone marrow function, and radiologically measurable NPC were eligible., Results: Twenty-five chemonaïve and 27 previously treated patients were enrolled. The overall response rate was 28% [95% confidence interval (CI) 14% to 48%] for the chemonaïve and 48% (95% CI 31% to 66%) for previously treated patients. Toxicities greater than or equal to grade 3 occurred in 15 (60%) chemonaïve and 13 (48%) previously treated patients. Neutropenia was uncommon in chemonaïve patients, but occurred in 37% of previously treated patients. The median time to progression was 3.6 months (range 0.9-7.9) for chemonaïve and 5.1 months (0.9-13.1) for previously treated patients. Median overall survival time was 7.2 months (1.4-15.6) and 10.5 months (2.4-15.0) for chemonaïve and previously treated patients, respectively., Conclusions: Gemcitabine has moderate activity in NPC with minimal toxicity, and is also an effective salvage agent for patients who have failed or progressed after treatment with other agents.

Imaging plays an important role in the staging of carcinoma of the nasopharynx. Accurate staging is necessary as the treatment is directly dependent on stage. Clinical examination provides information on mucosal involvement but is unable to determine the deep extension or presence of skull base invasion or intracranial spread. The 1997 International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC) staging manuals were a collaborative project that provided a unified classification for nasopharyngeal carcinoma (NPC). The majority of staging can be identified only on imaging and not by clinical examination. The intent of this article is to provide information on the specific imaging findings that will directly affect the stage and treatment of NPC.

This study reviewed all work-related burn injuries within the period 1 April 1992 to 31 March 1993 for the purpose of establishing data on occupational burns in Singapore to identify the specific at-risk population and formulate prevention strategies. All 163 patients who were admitted to the Burns Centre, Singapore General Hospital, as a result of burns suffered in the workplace were reviewed using the World Health Organisation Burns Data Protocol. Burns data recorded included demography, industrial sector involved, aetiology, extent of injury and eventual outcome in terms of mortality and morbidity. Occupational burns accounted for 45% of all admissions to the Burns Centre. Male workers in the 20 to 40-year age group predominated with 90% of admissions. The most common aetiology was flame burns and explosions (52.8%) followed by scalds (24.5%) and electrical (10.4%), chemical (6.1%) and contact (6.1%) burns. The average body surface area (BSA) involved was 8% (range 0.25% to 90%). Twenty-seven patients suffered full-thickness burns and the average area of involvement was 2% (range 0.25% to 90%). The most common anatomical regions involved were the upper limbs (46.3%) followed by lower limbs (31.9%). Eighteen patients (11.0%) sustained major burns requiring fluid resuscitation and 39 patients (23.9%) sustained respiratory burns. Seven patients died, giving a mortality rate of 4.3%. The average BSA for these patients was 46.4% and all had respiratory burns. In all, occupational burns accounted for 2011 patient-days of hospitalization, 630,637 lost days at work and inpatient treatment costs amounting to S $1.32 million.(ABSTRACT TRUNCATED AT 250 WORDS)

The lung is a common site for cancer to occur, for both primary as well as metastases. The presence of such tumours can give rise to symptoms such as haemoptysis, cough, breathlessness and pneumonia. In most cases, treatment is strictly for palliation. We present a case report of a patient with an endobronchial metastasis from a primary hypernephroma which recurred following external beam radiotherapy. He was treated with a single fraction of intraluminal brachytherapy to a dose of 10Gy at 1 cm from the axis on a High Dose Rate Ir192 Remote Afterloading Machine. There were no adverse effects following treatment. On follow-up 7 months later, the patient did not have any further recurrence of breathlessness although his disease had progressed at other sites.

Cancer of the oesophagus is the sixth commonest cancer in males in Singapore. The majority occur in the elderly and patients are often debilitated at presentation. Treatment is often aimed at palliation only. In this article, the preliminary results of 15 patients treated solely on a high dose rate remote afterloading Gammamed brachytherapy machine with an Iridium 192 (Ir192) source are reported. The patients were given 15 Gray (Gy) in a single or two 7.5 Gray fractions. All the patients treated had some improvement of their dysphagia, and seven out of 11 (63%) evaluable patients had symptom improvement lasting at least 11 weeks.

Research output in academic institutions need critical and objective assessment. Publications are an important avenue by which research by an academic can be evaluated. Journals in which such publications appear may be ranked and weight age given to publications in highly ranked journals. The number of citations of an academic's work by peers is another assessment of quality of research output. Firstly subjective peer assessment although flawed by interpersonal bias has its merits especially when evaluation is by an outsider of the institution.

Surgical procedures for exposure of the upper third of the fibula have been known to cause weakness of the long extensor of the big toe post-operatively. The authors present three representative cases of surgically induced dropped big toe. From cadaveric dissection, an anatomic basis was found for this phenomenon. The tibialis anterior and extensor digitorum longus muscles have their origin at the proximal end of the leg and receive their first motor innervation from a branch that arises from the common peroneal or deep peroneal nerve at about the level of the neck of the fibula. However, the extensor hallucis longus muscle originates in the middle one-third of the leg and the nerves innervating this muscle run a long course in close proximity to the fibula for up to ten centimeters from a level below the neck of the fibula before entering the muscle. Surgical intervention in the proximal one-third of the fibula just distal to the origin of the first motor branch to the tibialis anterior and extensor digitorum longus muscles carries a risk of injury to the nerves innervating the extensor hallucis longus.

In recent years the distally pedicled radial forearm flap has proved to be a versatile technique for resurfacing the hand. The venous drainage of this flap, however, has remained a puzzle. Various explanations have been suggested, including bypass of the valves by collateral veins and by crossover between the venae comitantes. However, venous drainage must be against the direction of the valves in at least one segment of the veins. The question of reversed venous flow and how it may be achieved reliably is addressed in this study. Timmons has postulated three criteria which all must be satisfied for reversal of venous flow. These criteria, namely higher proximal venous pressure, denervation of the valves, and the filling of the venous segments may be achieved satisfactorily if a few precautions are taken and certain technical manoeuvres performed. The criteria were re-examined in the light of known physiological phenomena. In addition, certain pertinent anatomical facts which arose from our cadaveric studies and which may be exploited to advantage are discussed. Our studies have led to greater understanding of reversed venous flow and to greater success with this flap in our clinical practice.

The blood supply to the skin of the anterior leg was studied in 10 fresh cadavers. Particular attention was paid to the intermuscular septal blood vessels, which emerge in the cleft between tibialis anterior and extensor hallucis longus and extensor digitorum longus muscles. With this anatomical knowledge, the reverse-pedicled anterior tibial fasciocutaneous flap was designed and transferred clinically to cover lower leg and foot defects in 6 patients. Three case reports are detailed. The factors which allow a distally based flap to be raised in the lower leg against the direction of venous valves are also described. The versatility of this new flap in the reconstruction of defects of the lower leg and foot is discussed.

A case of simultaneous dislocations of the interphalangeal and carpometacarpal joints of the thumb after a fall is described. We believe this is a unique situation not reported before in the literature. The results of operative intervention of the open IP joint and closed CMC joint dislocations resulted in a stable pain-free thumb with a good range of motion.

A case is reported of the reconstruction of a continent anus after an abdominoperineal resection for a patient who presented with a Dukes B adenocarcinoma at 4.5 cm from the anal verge. After a radical excision, the perineal colostomy was sited orthotopically. The right gracilis muscle, completely detached from the thigh except for the neurovascular pedicle, was wrapped around the neorectum at the original level of the levator ani, in an alpha loop configuration. The free ends of the alpha loop pointing anteriorly were sutured to the public bone. Thus the 80 degrees ano-rectal angle was reconstructed. A temporary transverse colostomy was also performed. After closure of the colostomy at eight weeks, the patient was immediately continent of soft stools without a learning period. Pressure studies of the new sphincter are also reported.

In this study the efficacy of preserving microvascular heterografts with glutaraldehyde tanning was investigated. These were compared with glutaraldehyde-tanned autografts. Previous studies have found that untreated autograft veins maintain a 95% patency rate, whilst untreated heterograft veins (Group 1) had a 15% patency rate at 4 weeks in this study. Autogenous glutaraldehyde-tanned rabbit carotid arterial grafts (Group 2) and glutaraldehyde-tanned human chorionic veins (Group 3) were interposed in rabbit femoral or carotid arteries. Fifty per cent and 75% patency rates were achieved respectively at 4 weeks. The low patency rate of the autogenous group suggests that the glutaraldehyde tanning technique itself is largely responsible for the low patency of glutaraldehyde-tanned human chorionic veins rather than any immunological response. Therefore if human chorionic veins are to be used as a readily available preserved microvascular graft, further investigation is required to develop another technique which will reduce antigenicity without promoting thrombosis.

The blood supply to the skin of the perineum, medial groin, and upper thigh was studied in fresh female cadavers. The pudendal-thigh flap was designed as a result to reconstruct the vagina. The flaps are raised bilaterally in the groin crease just lateral to the labia majora and then are transposed toward the midline and sutured together to form a skin-lined cul-de-sac which opens at the introitus. The technique has been used successfully in three patients to reconstruct the vagina. The first patient, an adult, was reconstructed after total pelvic exenteration for malignancy, while two children had reconstructions for congenital vaginal anomalies. This technique is superior to currently available methods because it is simple and reliable. No stents or dilators are needed. It is safe technique without complications in our hands. The reconstructed vagina has a natural angle for intercourse and is sensate. The donor scars in the groin are well hidden.