Effect of dietary vitamin C on gastric cancer risk in the Korean population

AIM: To investigate the effects of dietary vitamin C and foods containing vitamin C on gastric cancer risk.METHODS: Our study included 830 control subjects and 415 patients. Data regarding demographics, medical history, and lifestyle, including dietary and nutrient intake, were collected using reliable selfadministered questionnaires. Dietary intake information was collected from the participants using a food frequency questionnaire that has been previously reported as reliable and valid. A rapid urease test and a histological evaluation were used to determine the presence of Helicobacter pylori(H. pylori) infection. Twenty-three vitamin C-contributing foods were selected, representing over 80% of the cumulative vitamin C contribution. RESULTS: In analyses adjusted for first-degree family history of gastric cancer, education level, job, household income, smoking status, and regular exercise, an inverseassociation between vitamin C intake and gastric cancer risk was observed for the highest(≥ 120.67 mg/d) vs the lowest(< 80.14 mg/d) intake category [OR(95%CI): 0.64(0.46-0.88)], with a significant trend across the three intake categories(P = 0.007). No protective effect of vitamin C was detected after stratification by gender. No effect of vitamin C intake on the gastric cancer incidence was found in either men or women infected with H. pylori. Vitamin C-contributing foods, including cabbage [0.45(0.32-0.63), 0.50(0.34-0.75), 0.45(0.25-0.81)], strawberries [0.56(0.40-0.78), 0.49(0.32-0.74), 0.52(0.29-0.93)], and bananas [0.40(0.29-0.57), 0.41(0.27-0.62), 0.34(0.19-0.63)], were protective factors against the risk of gastric cancer based on the results of the overall adjusted analyses and the results for men and women, respectively.CONCLUSION: A protective effect of vitamin C and vitamin C-contributing foods against gastric cancer was observed. Further studies using larger sample sizes are required to replicate our results.

Epstein-Barr virus and the origin of Hodgkin lymphoma

Although Epstein-Barr virus(EBV)is present in the malignant Hodgkin/Reed-Sternberg(HRS)cells of a proportion of cases of classical Hodgkin lymphoma(c HL),how the virus contributes to the pathogenesis of this disease remains poorly defined.It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required.This article reviews what is known about the contribution of EBV to the pathogenesis of c HL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.

International validation of the Chinese University Prognostic Index for staging of hepatocellular carcinoma: a joint United Kingdom and Hong Kong study

The outcome of hepatocellular carcinoma(HCC) patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index(CUPI) for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer(BCLC) classification and the Cancer of the Liver Italian Program(CLIP). To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom(UK; n = 567; 2006-2011) and Hong Kong(HK; n = 517; 2007-2012). The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index(C-index) and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. For the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. For those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be optimal for those undergoing palliative treatment. A more precise staging system for early-stage disease patients is required.

Acceptance on colorectal cancer screening upper age limit in South Korea

BACKGROUND The Korea National Cancer Screening Program currently provides screening for colorectal cancer(CRC)for adults older than 50 years with no upper age limit.In general,people are likely to only pay attention to the benefits of cancer screening and to neglect its risks.Most consider the benefits of cancer screening as being far greater than the risks and are unaware that any potential benefits and harms can vary with age.AIM To report acceptance of an upper age limit for CRC screening and factors associated therewith among cancer-free individuals in Korea.METHODS The present study analyzed data from the Korea National Cancer Screening Survey 2017,a nationally representative random sample of 4500 Korean individuals targeted for screening for the five most common types of cancer.A total of 1922 participants were included in the final analysis.The baseline characteristics of the study population are presented as unweighted numbers and weighted proportions.Both univariate and multivariate logistic regression models were developed to examine factors related with acceptance of an upper age limit for CRC screening;subgroup analysis was also applied.RESULTS About 80%(1554/1922)of the respondents agreed that CRC screening should not be offered for individuals older than 80 years.Specifically,those who had never been screened for CRC had the highest acceptance rate(91%).Overall,screening history for CRC[screened by both fecal occult blood test and colonoscopy,adjusted odds ratio(aOR)=0.33,95%CI:0.22-0.50]and other cancers(aOR=0.55,95%CI:0.34-0.87),as well as a family history of cancer(aOR=0.66,95%CI:0.50-0.87),were negatively associated with acceptance of an upper age limit for CRC screening.In contrast,metropolitan residents(aOR=1.86,95%CI:1.29-2.68)and people who exercised regularly(aOR=1.42,95%CI:1.07-1.89)were more likely to accept an upper age limit.After subgrouping,we found gender,marital status,and lifetime smoking history among never-screened individuals and residential region,family history of cancer,and physical activity among never-screened individuals to be associated with acceptance of an upper age limit.CONCLUSION This study describes acceptance of an upper age limit for CRC screening and factors associated with it,and provides perspectives that should be considered,in addition to scientific evidence,when developing population-based cancer screening policies and programs.

Management of Phylloid Sarcomas: A Retrospective Study of 12 Cases

Background: Phylloid sarcomas are rare. There is not enough data to codify the management. Objectives: The objective was to study the clinical and therapeutic aspects and the fate of patients after a follow-up of at least 4 years. Thus contributing to the limited body of knowledge on these tumors. Methods: a retrospective analysis of the files from 2013 to 2017 was carried out and patients were followed up until 2021at Hassan II Hospital. Epidemiological, clinical and therapeutic aspects were studied. Survival was calculated using the Kaplan-Meier method. Results: We collected 12 charts of patients treated for phyllodeal sarcoma from 2013 to 2017. The median age was 43 years. The circumstance of discovery was marked by the presence of nodule in all patients. The coupled echo-mammography examination classified the nodules, ACR 4 in 7 patients and ACR 3 in 3 and ACR 5 in 2 patients. Histological examination revealed a phylloid sarcoma in 11 patients and a borderline phylloid tumor in 1 patient. All patients had radical surgery with positive margins in 2 patients, 16.66%. One patient had revision surgery. Histological examination of the surgical specimens showed phylloid sarcoma on all specimens. All patients had adjuvant radiotherapy with doses of 50 Gy in 25 fractions of 2 Gy and a boost of 10 Gy was done in one patient. The median spread of radiotherapy was 37 days. Grade 1 and 2 skin toxicities were noted in 5 and 3 patients respectively. The median time from surgery to radiotherapy was 2.95 months. 3 patients relapsed after 13.6 months of follow-up. The recurrence-free survival at 1 and 3 years was 83% and 75% respectively. Overall survival at 3 and 5 years was 83% and 75% respectively. Conclusion: This is a rare entity which requires randomized trials to codify its management. It would seem that the multidisciplinary approach, associating surgery ± radiotherapy, is a good option.

Epstein-Barr virus and nasopharyngeal carcinoma

Since its discovery 50 years ago,Epstein-Barr virus(EBV)has been linked to the development of cancers originating from both lymphoid and epithelial cells.Approximately 95%of the world’s population sustains an asymptomatic,life-long infection with EBV.The virus persists in the memory B-cell pool of normal healthy individuals,and any disruption of this interaction results in virus-associated B-cell tumors.The association of EBV with epithelial cell tumors,specifically nasopharyngeal carcinoma(NPC)and EBVpositive gastric carcinoma(EBV-GC),is less clear and is currently thought to be caused by the aberrant establishment of virus latency in epithelial cells that display premalignant genetic changes.Although the precise role of EBV in the carcinogenic process is currently poorly understood,the presence of the virus in all tumor cells provides opportunities for developing novel therapeutic and diagnostic approaches.The study of EBV and its role in carcinomas continues to provide insight into the carcinogenic process that is relevant to a broader understanding of tumor pathogenesis and to the development of targeted cancer therapies.

Epstein-Barr virus and Burkitt lymphoma

In 1964,a new herpesvirus,Epstein-Barr virus(EBV),was discovered in cultured tumor cells derived from a Burkitt lymphoma(BL)biopsy taken from an African patient.This was a momentous event that reinvigorated research into viruses as a possible cause of human cancers.Subsequent studies demonstrated that EBV was a potent growth-transforming agent for primary B cells,and that all cases of BL carried characteristic chromosomal translocations resulting in constitutive activation of the c-MYC oncogene.These results hinted at simple oncogenic mechanisms that would make Burkitt lymphoma paradigmatic for cancers with viral etiology.In reality,the pathogenesis of this tumor is rather complicated with regard to both the contribution of the virus and the involvement of cellular oncogenes.Here,we review the current understanding of the roles of EBV and c-MYC in the pathogenesis of BL and the implications for new therapeutic strategies to treat this lymphoma.

Changes in human hepatic metabolism in steatosis and cirrhosis

AIM To understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance(NMR) metabolomics analysis to human liver tissue.METHODS We have carried out pilot study using 1H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis(NASH) or alcohol-related liver damage(ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver injuries. RESULTS Changes in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARLD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARLD samples were also detected using our approach.CONCLUSION Our high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance.

Hepatocellular carcinoma,decompensation,and mortality based on hepatitis C treatment:A prospective cohort study

BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus(HCV)infection after treatment with interferon-based therapy(IBT)or directacting antivirals(DAA)are limited in many Asian countries.AIM To elucidate the incidences of hepatocellular carcinoma(HCC)and death/transplantation based on treatment with IBT or DAA,to compare the outcomes of the sustained virologic response(SVR)to IBT and DAA,and to investigate outcome-determining factors after SVR.METHODS This cohort included 2054 viremic patients(mean age,57 years;46.5%male;27.4%with cirrhosis)prospectively enrolled at seven hospitals between 2007 and 2019.They were classified as the untreated group(n=619),IBT group(n=578),and DAA group(n=857).Outcomes included the incidences of HCC and death/transplantation.The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution.A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation,followed by propensity score matching to confirm the results.RESULTS During a median of 4.1 years of follow-up,HCC and death/transplantation occurred in 113 and 206 patients,respectively,in the entire cohort.Compared with the untreated group,the incidences of HCC and death/transplantation were significantly lower in the IBT group[adjusted hazard ratio(aHR)0.47,95%CI:0.28-0.80 and aHR 0.28,95%CI:0.18-0.43,respectively]and the DAA group(aHR 0.58,95%CI:0.35-0.96,and aHR 0.19,95%CI:0.20-0.68,respectively).Among 1268 patients who attained SVR with IBT(n=451)or DAA(n=816),the multivariable-adjusted analysis showed no differences in the risks of HCC(HR 2.03;95%CI:0.76-5.43)and death/transplantation(HR 1.38;95%CI:0.55-3.49)between the two groups.This was confirmed by a propensity score-matching analysis.Independent factors for HCC after SVR were age,genotype 1,and the presence of cirrhosis.CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection.The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.

4-1BB-4-1BBL cis-interaction contributes to the survival of selfreactive CD8^(+)T cell

4-1BB is an inducible receptor expressed on activated T cells,while its ligand,4-1BBL,is mainly expressed in antigen-presenting cells and macrophages[1,2].To the best of our knowledge,ligandmediated transactivation of 4-1BB is responsible for the survival and immune effector functions of T cells.

Chronic activation of 4-1BB signaling induces granuloma development in tumor-draining lymph nodes that is detrimental to subsequent CD8^(+)T cell responses

The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy.However,the adverse side effects associated with agonist antibodies have hindered their clinical development.Here,we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs.We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1^(+)CD8^(+)T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8^(+)T cells,which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction.However,repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes(TDLNs)of mice due to recruitment and accumulation of macrophages via the CD8^(+)T cell-IFN-γaxis.This was accompanied by excessive lymph node swelling,which impaired the sequential activation of CD8^(+)T cells.Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing,which should be considered during the clinical development of immunomodulating therapy.

卵巢癌的诊断

卵巢癌是全球女性第七位最常见的癌症，2012年，有23．9万新发病例。和许多其他类型的癌症一样，不同地区卵巢癌的发病率和病死率差异很大，经济发达地区的发病率更高。卵巢癌发病率最高的年龄组是50-70岁，75％的病例发生在55岁以后3080％的病例在出现症状时已处于疾病晚期，5年生存率很低。在英国，各分期卵巢癌总的5年生存率为46％。

减少足月妊娠初产妇第一产程延长行剖宫产术的最佳处理策略

分娩过程常分为3个产程。第一产程和第二产程的时间取决于产妇的分娩次数。图1是英国国家健康与临床优选研究所（NICE）定义的产程阶段和预期持续时间。初产妇的产程往往比经产妇更长。产程延长可由子宫收缩乏力引起，或由胎儿的大小、先露部和胎方位与阻碍阴道分娩的母体骨盆的关系等因素引起。子宫收缩功能障碍影响11％～30％初产妇的产程，也是本文关注的重点。

Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells

The homeostatic balance between effector T cells and regulatory T cells(Tregs)is crucial for adaptive immunity;however,epigenetic programs that inhibit phosphorylation to regulate Treg development,peripheral expression,and suppressive activity are elusive.Here,we found that the Ssu72 phosphatase is activated by various T-cell receptor signaling pathways,including the T-cell receptor and IL-2R pathways,and localizes at the cell membrane.Deletion of Ssu72 in T cells disrupts CD4+T-cell differentiation into Tregs in the periphery via the production of high levels of the effector cytokines IL-2 and IFNγ,which induce CD4+T-cell activation and differentiation into effector cell lineages.We also found a close correlation between downregulation of Ssu72 and severe defects in mucosal tolerance in patients.Interestingly,Ssu72 forms a complex with PLCγ1,which is an essential effector molecule for T-cell receptor signaling as well as Treg development and function.Ssu72 deficiency impairs PLCγ1 downstream signaling and results in failure of Foxp3 induction.Thus,our studies show that the Ssu72-mediated cytokine response coordinates the differentiation and function of Treg cells in the periphery.