Africa ; epidemiology ; Asia, Southeastern ; epidemiology ; Carcinoma ; Epstein-Barr Virus Infections ; complications ; epidemiology ; virology ; Herpesvirus 4, Human ; pathogenicity ; Humans ; Middle East ; epidemiology ; Nasopharyngeal Neoplasms ; epidemiology ; etiology ; virology

China is a country with high incidence of gastric cancer, most of which are advanced gastric cancer, accounting for about half of the new cases in the world. Environmental factors play a crucial role in the occurrence and development of gastric cancer. Helicobacter pylori and Epstein Barr virus(EBV) infection have been confirmed as one of the important pathogenic factors of gastric cancer. With the development and application of molecular biology and sequencing technology, molecular typing based on patient genetic characteristics has been proposed to guide accurate treatment and predict prognosis. Surgery is the cornerstone of gastric cancer treatment. Laparoscopy has been developing rapidly in the past 20 years on account of its clinical application advantages such as minimally invasive and magnified visual field and refined anatomy, making it one of the standard treatment options for early gastric cancer, with its indications for the treatment of gastric cancer continuously expanding. The application of endoscopic treatment and reduction surgery for early gastric cancer further improves the quality of life of patients, and surgical treatment of gastric cancer tends to be precise and minimally invasive. The comprehensive treatment of surgery combined with radiotherapy and chemotherapy is a standard treatment of local advanced gastric cancer. The exploration of related drugs and treatment models is the current research hotspot, and the development and application of targeted therapy and immunotherapy provide more choices in this field. The treatment of advanced gastric cancer is focused on the exploration of chemotherapy, targeted therapy and immunotherapy. Some studies have shown good prospects and provided more opportunities for conversion therapy. This article will share the new developments in the field of gastric cancer research in 2018.
China ; epidemiology ; Combined Modality Therapy ; Epstein-Barr Virus Infections ; complications ; Helicobacter Infections ; complications ; Helicobacter pylori ; Herpesvirus 4, Human ; Humans ; Laparoscopy ; Prognosis ; Stomach Neoplasms ; epidemiology ; etiology ; pathology ; therapy

OBJECTIVETo compare the Epstein-Barr virus (EBV) infection rates and the frequencies of wt-LMP1 and del-LMP1 EBV variants detected singly or dually among the four types of nasopharyngeal carcinoma (NPC) and to illustrate the possible role of del-LMP1 gene in nasopharyngeal carcinogenesis.

METHODSEBER in situ hybridization was performed in 117 NPCs, including 48 non-keratinizing carcinomas (NKCs), 25 keratinizing squamous cell carcinomas (KSCCs), 5 adenosquamous carcinomas (ASCs), 6 mucoepidermoid carcinomas (MECs) and 33 adenocarcinomas (ACs). Nested PCR for demonstration of EBV LMP1 gene was performed on the tissue samples collected from 99 EBER-positive carcinoma cases and the peripheral blood mononuclear cells (PBMCs) of 53 healthy adults (HAs).

RESULTSAs indicated by EBER in-situ hybridization, the EBV infection rates in both of 48 NKCs and 25 KSCCs were 100%; and the infection rates of 11 ASCs/MECs and 33 ACs were 9/11 and 51.5% (17/33), respectively. Worthy to note was that most of the NKC cells were EBER-positive while only a small number of EBER-positive neoplastic cells could be found in 17 ACs. The percentage of del-LMP1 EBV variant detected singly in NKCs (85.4%, 41/48) was not only significantly higher than that in PBMCs of 46 HAs (8.7%, 4/46) but also significantly higher than those detected in KSCCs (16.0%, 4/25). The dual infection rate of wt-LMP1 and del-LMP1 variants detected in KSCCs (56.0%, 14/25) was significantly higher than that of NKCs (12.5%, 6/48). The majority of the EBV detected in AC tissues (12/17) and HAs' PBMCs (34/46, 73.7%) were of dual wt-LMP1 and del-LMP1 variants.

CONCLUSIONSThe EBV infection rates are significantly different among 3 major histological categories, namely, NKC/KSCC, ASC/MEC and AC. Though NKCs and KSCCs are always consistently associated with EBV, the single del-LMP1 EBV variant detected in NKCs is predominant over that in KSCCs and most of the KSCCs contain dual wt-LMP1 and del-LMP1 EBV variants. The EBV of the del-LMP1 variant might play a crucial role in carcinogenesis of NKC.

Adult ; Epstein-Barr Virus Infections ; epidemiology ; Female ; Gene Deletion ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; etiology ; virology ; Viral Matrix Proteins ; genetics

Recently, cases with typical clinical manifestations of infectious mononucleosis are increasing in Korea. So, to evaluate the recent epidemiology of EBV infection in Korea, we performed EBV serologic antibody tests for IgG antibody to EBV-viral capsid antigen (VCA) and antibody to EBV-associated nuclear antigen (EBNA) among the 108 healthy Korean infants and children whose ages were from newborn to 15 years old. And the results were as follows; 1) The positive rates of anti-VCA IgG 100% in newborn, 90% in 2 to 6 months, 20% in 7 to 12 months, 60% in 1 to 2 years, 77.3% in 3 to 4 years, 88.5% in 5 to 6 years, 90% in 7 to 9 years, and 100% in 10 to 15 years of age, respectively. 2) The anti-VCA IgG titers ranged from 1:20 to 1:1280. 3) The positive rates of anti-EBNA were 100% in newborn, 60% in 2 6 months, 10% in 7 to 12 months, 60% in 1 to 2 years, 68.2% in 3 to 4 years, 84.5% in 5 to 6 years, 70% in 7 to 9 years, and 100% in 10 to 15 years of age, respectively. 4) The anti-EBNA titers ranged from 1:2 to 1:128. According to these data, the age of primary infection of EBV has increased compared to the previous data in Korean children.
Adolescent ; Capsid ; Child* ; Epidemiology ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Immunoglobulin G ; Infant ; Infant, Newborn ; Infectious Mononucleosis ; Korea ; Prevalence*

OBJECTIVE: To detect the Epstein-Barr virus (EBV) viral load of children after hematopoietic stem cell transplantation (HSCT) using chip digital PCR (cdPCR). METHODS: The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain. The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses (herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6, and human herpesvirus 7). From May 2019 to September 2020, 64 serum samples of children following HSCT were collected. EBV infection and the viral load of serum samples were detected by cdPCR. The epidemiological characteristics of EBV infections were analyzed in HSCT patients. RESULTS: The limit of detection of EBV cdPCR was 110 copies/mL, and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid. The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain, and both were more sensitive than that of quantitative PCR. Using cdPCR, the incidence of EBV infection was 18.75% in 64 children after HSCT. The minimum EBV viral load was 140 copies/mL, and the maximum viral load was 3,209 copies/mL using cdPCR. The average hospital stay of children with EBV infection (184 ± 91 days) was longer than that of children without EBV infection (125 ± 79 days), P = 0.026. CONCLUSION EBV cdPCR had good sensitivity and specificity. The incidence of EBV infection was 18.75% in 64 children after HSCT from May 2019 to September 2020. EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.
Child ; DNA, Viral/analysis* ; Epstein-Barr Virus Infections/epidemiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Herpesvirus 4, Human/genetics* ; Humans ; Real-Time Polymerase Chain Reaction ; Viral Load

This study is to identify the spectrum of Epstein-Barr virus (EBV)-positive lymphoproliferative diseases (LPD) and relationships between these diseases in Korea. The EBV status and clinicopathology of 764 patients, including acute EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV (CAEBV) infections, B-LPD arising in chronic latent EBV infection, T & natural killer (NK) cell non-Hodgkin's lymphomas (NHL), B-NHLs, and Hodgkin's lymphomas (HD), were analyzed. T or NK cell NHLs were the most common forms of EBV-positive NHLs (107/167, 64%); among these, nasal-type NK/T cell lymphomas were the most common (89/107, 83%). According to the age, Burkitt's lymphoma was the most common in early childhood; in teenagers, chronic (active) EBV infection-associated LPD was the most common type. The incidence of NK/T cell lymphoma began to increase from the twenties and formed the major type of EBV-associated tumor throughout life. Diffuse large B cell lymphoma formed the major type in the sixties and seventies. In conclusion, primary infections in early childhood are complicated by the development of CAEBV infections that are main predisposing factors for EBV-associated T or NK cell malignancies in young adults. In old patients, decreased immunity associated with old age and environmental cofactors may provoke the development of peripheral T cell lymphoma, unspecified, and diffuse large B cell lymphoma.
Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Epstein-Barr Virus Infections/*diagnosis/*epidemiology ; Herpesvirus 4, Human/*metabolism ; Humans ; Infant ; Korea ; Lymphoproliferative Disorders/*diagnosis/epidemiology/*virology ; Middle Aged ; Treatment Outcome

Among all head and neck (H&N) cancers, nasopharyngeal carcinoma (NPC) represents a distinct entity regarding epidemiology, clinical presentation, biological markers, carcinogenic risk factors, and prognostic factors. NPC is endemic in certain regions of the world, especially in Southeast Asia, and has a poor prognosis. In Indonesia, the recorded mean prevalence is 6.2/100 000, with 13 000 yearly new NPC cases, but otherwise little is documented on NPC in Indonesia. Here, we report on a group of 1121 NPC patients diagnosed and treated at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia between 1996 and 2005. We studied NPC incidence among all H&N cancer cases (n=6000) observed in that period, focusing on age and gender distribution, the ethnic background of patients, and the disease etiology. We also analyzed most prevalent signs and symptoms and staging of NPC patients at first presentation. In this study population, NPC was the most frequent H&N cancer (28.4%), with a male-to-female ratio of 2.4, and was endemic in the Javanese population. Interestingly, NPC appeared to affect patients at a relatively young age (20% juvenile cases) without a bimodal age distribution. Mostly, NPC initiated in the fossa of Rosenmuller and spreaded intracranially or locally as a mass in the head. Occasionally, NPC developed at the submucosal level spreading outside the anatomic limits of the nasopharynx. At presentation, NPC associated with hearing problems, serous otitis media, tinnitus, nasal obstruction, anosmia, bleeding, difficulty in swallowing and dysphonia, and even eye symptoms with diplopia and pain. The initial diagnosis is difficult to make because early signs and symptoms of NPC are not specific to the disease. Early-age Epstein-Barr virus (EBV) infection combined with frequent exposure to environmental carcinogenic co-factors is suggested to cause NPC development. Undifferentiated NPC is the most frequent histological type and is closely associated with EBV. Expression of the EBV-encoded latent membrane protein 1(LMP1) oncogene in biopsy material was compared between NPC patients of <30 years old and those of ≥30 years old, matched for sex and tumor stage. Higher LMP1 expression in patients of <30 years old was observed, which was related to more locoregional progressivity. Increased medical awareness of prevailing early stage signs and symptoms coupled to use of EBV-related diagnostic tumor markers may lead to down-staging and timely treatment to improve survival of patients with this aggressive disease.
Adolescent ; Adult ; Age Distribution ; Aged ; Child ; Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Incidence ; Indonesia ; epidemiology ; ethnology ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; epidemiology ; ethnology ; pathology ; virology ; Sex Factors ; Viral Matrix Proteins ; metabolism ; Young Adult

This study aims to investigate the genetic characteristics of BZLF1 gene and its promoter Zp of the epidemic strains in children with primary Epstein-Barr virus (EBV)-associated diseases. Total DNA was extracted from the peripheral blood of 134 children with EBV-associated infectious mononucleosis (EBV-IM) and 32 children with EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) who were admitted to Beijing Children's Hospital from 2006 to 2011. The EBNA3C, BZLF1, and Zp genes were amplified by PCR assay. Typing of EBV was performed according to the size of the amplification product of EBNA3C gene; the amplification products of BZLF1 and Zp genes were subjected to direct sequencing, and sequence analysis was performed using BioEdit 7. 0. 9. The results were as follows: (1) EBV-1 was present in 140 samples (97.2%, 140/144) and EBV-II in 4 samples (2.8%, 4/144). (2) Three BZLF1 genotypes and their 12 subtypes (including 6 newly found subtypes) were detected in this study; there were no significant differences in the frequencies of BZLF1-A and BZLF1-B between the children with EBV-IM and EBV-HLH (P = 0.083); BZLF1-A1 was the dominant genotype in children with EBV-associated diseases; t BZLF1-A mostly had three 29-bp repeats in the first intron of BZLF1 gene, and BZLF1-B mostly had 30-bp repeats (P = 0.000), with the number of repeats varying from 1 to 13. (3) Four Zp genotypes were detected in this study, including Zp-P, Zp-V3, Zp-V4, and Zp-V1; there were no significant differences in the frequencies of these Zp genotypes between children with EBV-IM and EBV-HLH (P = 0.272, 0.252, 1.0, and 1.0, respectively). (4) The linkage analysis of BZLF1 gene and its promoter Zp showed that BZLF1-A1 was highly associated with Zp-V3 (P = 0.000), while BZLF1-B4 with Zp-P (P = 0.000); EBV-I + BZLF1 A1 was highly associated with Zp-V3 (P = 0.000), while EBV-I+BZLF1-B4 with Zp-P (P = 0.000). The conclusions are as follows: (1) BZLF1-A1 is the dominant genotype in children with EBV-associated diseases; there are mostly 29-bp repeats in the first intron of BZLF1 gene for BZLF1-A genotype and 30-bp repeats for BZLF1-B genotype. (2) Zp-P and Zp-V3 are dominant Zp genotypes of EBV in children, which shared similar detection rates. (3) BZLF1-A1 is highly associated with Zp-V3, while BZLF1-B4 with Zp-P; EBV-I+BZLF1-A1 is highly associated with Zp-V3, while EBV-I+BZLF1-B4 with Zp-P.
Child ; Child, Preschool ; China ; epidemiology ; Epstein-Barr Virus Infections ; epidemiology ; virology ; Female ; Genotype ; Herpesvirus 4, Human ; genetics ; physiology ; Humans ; Infant ; Infant, Newborn ; Introns ; genetics ; Male ; Promoter Regions, Genetic ; genetics ; Repetitive Sequences, Nucleic Acid ; genetics ; Trans-Activators ; genetics

OBJECTIVETo study the clinicopathologic features of Hodgkin lymphoma (HL) occurring in northern China, association with Epstein-Barr virus (EBV) infection and concordance between EBV protein immunohistochemistry (IHC) and in-situ hybridization (ISH).

METHODSTwo hundred and thirty-five cases were collected and their HE and IHC slides were reviewed to confirm the diagnosis and sort of HLs. All cases were performed with IHC staining for LMP-1 protein and ISH of EBV-encoded RNAs (EBER) was done in 101 cases to detect the existence of EBV.

RESULTSThe incidence peak was between age 25 and 35 years, followed by another peak between age 56 to 60 years. There were 135 males and 100 females. The tumor involved lymph nodes in 217 cases, and extranodal sites in 18 cases. There were 3 cases of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and 232 cases of classical Hodgkin lymphoma. All tumors were stained for CD30, CD20, CD3. CD30 was expressed in 227 cases (96.6%), CD20 was expressed in 53 cases (22.5%) with different level of intensity. CD3 was expressed only in 1 case (0.4%). CD15 staining was performed in 224 cases and 117 (52.2%) cases were positive. PAX-5 were performed in 213 cases and 160 (75.1%) cases showed weak to moderate expressions. Two hundred and thirty-five cases were immunohistochemically stained with LMP1 and 72 (30.6%) cases were positive. Meanwhile, EBER ISH were applied in 101 cases, and 40 cases (39.6%) were found positive. LMP1 was expressed in 30 cases among those EBER-positive cases, while LMP1 was only detected in 5 cases of the EBER-negative cases. There was no statistically significantce between LMP1 IHC and EBER ISH by pared chi-square test (P = 0.3), the overall concordance rate was 85.2%.

CONCLUSIONSThere was a bimodal age distribution in our group of HL cases from the northern part of China, with slight male predominance and mainly nodal involvement. Nodular sclerosis (NS) and mixed cellularity (MC) were major histologic subtypes. When it was compared with the EBER ISH method in detection EBV infection of HL, the more economical and convenient LMP1 IHC showed both high degree of consistency and overall concordance rate.

Adult ; Age Distribution ; Antigens, CD ; analysis ; China ; epidemiology ; Epstein-Barr Virus Infections ; complications ; epidemiology ; Female ; Herpesvirus 4, Human ; genetics ; isolation & purification ; Hodgkin Disease ; immunology ; pathology ; virology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Incidence ; Male ; Middle Aged ; RNA, Viral ; analysis ; Sex Distribution

BACKGROUNDChronic active Epstein-Barr virus infection (CAEBV) has been previously reported to be sometimes associated with an aggressive clinical course. The characteristics of CAEBV in Mainland Chinese pediatric patients are largely unreported. The main aims of this survey were to recognize the clinical features of CAEBV in children and to explore its diagnostic criteria and risk factors.

METHODSA retrospective study was performed on 53 pediatric patients (36 boys and 17 girls) with CAEBV who were admitted to Beijing Children's Hospital between 2003 and 2007. All their medical records were reviewed and analyzed. For each patient, demographic, clinical, laboratory data and outcome were collected. Independent-samples t test was used for statistical analysis.

RESULTSThe age at onset of CAEBV was from 2 months to 14.6 years (mean (5.3+/-3.3) years). At the time of onset, 43.4% patients had an infectious mononucleosis-like symptom. Most patients exhibited intermittent fever (92.5%, 49/53), hepatomegaly (81.1%, 43/53) and splenomegaly (77.4%, 41/53). Life-threatening complications including hemophagocytic syndrome (24.5%, 13/53), interstitial pneumonia (24.5%, 13/53), hepatic failure (15.1%, 8/53) and malignant lymphoma (11.3%, 6/53) were also observed. The serum EBV DNA level in 23 patients with CAEBV was in the range of 5.05 x 10(2)-4.60 x 10(6) copies/ml with a mean value of 10(3.7) copies/ml. Many patients with CAEBV generally had continuous symptoms during the observational period. Eleven out of 42 patients (26.2%) died 7 months to 3 years after onset. Deceased patients were more likely to have had lower platelet counts and albumin levels than the living patients (P<0.05 for all comparisons).

CONCLUSIONSThe study reveals that CAEBV in Chinese pediatric patients has a severe clinical course and prognosis is poor. Thrombocytopenia and decreases in albumin might potentially be risk factors for a poor prognosis. EBV loads should be measured and tissue should be stained on hybridization probes for EBV-encoded small RNA (EBER) if a patient presents with the known symptoms of CAEBV.

Adolescent ; Age Distribution ; Child ; Child, Preschool ; China ; epidemiology ; Chronic Disease ; Epstein-Barr Virus Infections ; diagnosis ; epidemiology ; etiology ; pathology ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Risk Factors ; Serum Albumin ; analysis ; Thrombocytopenia ; complications