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.
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).
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.
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 .).
The Omicron variant is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in the serum of convalescent or ...vaccinated individuals to understand potential loss of protection against infection by Omicron. We previously established that a 50% plaque reduction neutralization antibody titer (PRNT
) ≥25.6 in our live virus assay corresponded to the threshold for 50% protection from infection against wild-type (WT) SARS-CoV-2. Here we show markedly reduced serum antibody titers against the Omicron variant (geometric mean titer (GMT) < 10) compared to WT virus 3-5 weeks after two doses of BNT162b2 (GMT = 218.8) or CoronaVac vaccine (GMT = 32.5). A BNT162b2 booster dose elicited Omicron PRNT
titers ≥25.6 in 88% of individuals (22 of 25) who previously received 2 doses of BNT162b2 and 80% of individuals (24 of 30) who previously received CoronaVac. However, few (3%) previously infected individuals (1 of 30) or those vaccinated with three doses of CoronaVac (1 of 30) met this threshold. Our findings suggest that countries primarily using CoronaVac vaccines should consider messenger RNA vaccine boosters in response to the spread of Omicron. Studies evaluating the effectiveness of different vaccines against the Omicron variant are urgently needed.
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.
We herein present an overview of the upcoming 5
edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms ...will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4
edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5
edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
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
mm
2
/s), ADC
0–1000
mean (0.77 ± 0.08 vs 1.00 ± 0.13 × 10
−3
mm
2
/s), ADC
300–1000
(0.63 ± 0.05 vs 0.86 ± 0.10 × 10
−3
mm
2
/s) and a higher
D
* mean (32.66 ± 4.79 vs 21.96 ± 5.21 × 10
−3
mm
2
/s) (all
p
< 0.001). No significant difference in the
f
mean was observed between the two groups (
p
= 0.216). The
D
and ADC
300–1000
mean had the highest AUC of 0.985 and 0.988, respectively, and the D mean of < 0.75 × 10
−3
mm
2
/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 ADC
300–1000
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.
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.
The hematoxylin–eosin (H&E) stain has stood the test of time as the standard stain for histologic examination of human tissues. This simple dye combination is capable of highlighting the fine ...structures of cells and tissues. Most cellular organelles and extracellular matrix are eosinophilic, while the nucleus, rough endoplasmic reticulum, and ribosomes are basophilic. This review discusses the spectrum, intensity, and texture of colors observed in H&E-stained slides to illustrate their value in surgical pathology diagnosis. Changes in color of the nuclei occur in the presence of nuclear pseudoinclusions (such as papillary thyroid carcinoma) or inclusions (such as viral infection, surfactant, immunoglobulin, and biotin). The color of the cytoplasm of spindly cells can provide clues to their nature, such as basophilic (fibroblast), eosinophilic (smooth muscle and others), and amphophilic (myofibroblast). Eosinophilic globules have diagnostic value for sclerosing polycystic adenosis of salivary gland, low-grade B-cell lymphoma, solid pseudopapillary tumor of pancreas, and inclusion body fibromatosis. Eosinophilic granules are characteristic of granular cells (lysosome-rich), oncocytic cells (mitochondria-rich), and cells with secretory products (including neuroendocrine cells). Eosinophilic crystals can be diagnostic of lymphoma/plasmacytoma and crystal-storing histiocytosis. Basophilic granules or inclusions are diagnostic of acinic cell carcinoma and malakoplakia (Michaelis–Gutmann bodies). Yellow or brown inclusions are characteristic of hyalinizing trabecular adenoma of thyroid (yellow bodies), brown bowel syndrome, and malignant melanoma. Extracellular eosinophilic deposits can be produced by many conditions, but amyloid and monoclonal immunoglobulin deposition disease are important considerations. Extracellular basophilic deposits may be seen in small cell carcinoma and systemic lupus erythematosus, but they differ in that the former is blue (nuclear material) while the latter is purple (nuclear material plus immunoglobulin).
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This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and ...presents new clinically relevant recommendations.
An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional.
Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease. Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers. Pharmacologic management: The group recommends that patients with bleeding ulcers with high-risk stigmata who have had successful endoscopic therapy receive high-dose proton-pump inhibitor (PPI) therapy (intravenous loading dose followed by continuous infusion) for 3 days. For these high-risk patients, continued oral PPI therapy is suggested twice daily through 14 days, then once daily for a total duration that depends on the nature of the bleeding lesion. Secondary prophylaxis: The group suggests PPI therapy for patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy for cardiovascular prophylaxis.
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