The Dynamic Changing Incidence of Gastric Cancer in Israel: Time for a National Surgical Management Committee?

BACKGROUND: There has been a general reduction over the last 20 years in the incidence within Israel of gastric cancer (GC). This has particularly been noted in the Jewish population with a slight increase in the incidence of cancer of the gastroesophageal junction among Jews of Sephardi origin. Given the diversity of individual ethnic subpopulations, the effects of GC incidence in second-generation immigrant Jews, particularly from high prevalence regions (e.g., the former Soviet Union, Iraq, and Iran), awaits determination. There are currently no national data on GC-specific mortality. The most recent available cross-correlated Israeli National Cancer Registry (INCR) and International Association for Cancer Research (IARC) incidence data for GC of the body and antrum in Israel are presented. Some of the challenges associated with GC monitoring in the changing Israeli population are discussed. We propose the establishment of a national GC management committee designed to collect demographic and oncological data in operable cases with the aim of recording and improving GC-specific outcomes. We believe that there is value in the development of a national surgical planning program, which oversees training and accreditation in a dynamic environment that favors the wider use of neoadjuvant therapies, minimally invasive surgery and routine extended (D2) lymphadenectomy. These changes should be supported by assessable enhanced recovery programs.

The risk and prognostic factors for brain metastases in esophageal cancer patients: an analysis of the SEER database.

BACKGROUND: Brain metastases were rare in esophageal cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, the present study investigated the incidence, risk and prognostic factors of brain metastases in esophageal cancer patients. METHODS: Retrieving esophageal cancer patients diagnosed between 2010 and 2018 from the SEER database, univariable and multivariable logistic and cox regression models were used to investigate the risk factors for brain metastases development and prognosis, respectively. The brain metastases predicting nomogram was constructed, evaluated and validated. The overall survival (OS) of patients with brain metastases was analyzed by Kaplan-Meier method. RESULTS: A total of 34,107 eligible esophageal cancer patients were included and 618 of them were diagnosed with brain metastases (1.8%). The median survival of the brain metastatic esophageal cancer patients was 5 (95% CI: 5-7) months. The presence of bone metastases and lung metastases were the homogeneously associated factors for the development and prognosis of brain metastases in esophageal cancer patients. Patients younger than 65 years, American Indian/Alaska Native race (vs. White), overlapping lesion (vs. Upper third), esophageal adenocarcinoma histology subtype, higher N stage, and liver metastases were positively associated with brain metastases occurrence. The calibration curve, ROC curve, and C-index exhibited good performance of the nomogram for predicting brain metastases. CONCLUSIONS: Homogeneous and heterogeneous factors were found for the development and prognosis of brain metastases in esophageal cancer patients. The nomogram had good calibration and discrimination for predicting brain metastases.

Racial disparities in provider recommendation for esophagectomy for esophageal carcinoma.

BACKGROUND: Racial disparities currently exist for the utilization rate of esophagectomy for Black patients with operable esophageal carcinoma. METHODS: A total of 37 271 cases with the American Joint Committee on Cancer clinical stage I, II, and III esophageal carcinoma that were reported to the National Cancer Database were analyzed between 2004 and 2016. A multivariable-adjusted logistic regression model was used to evaluate differences in the odds ratio of esophagectomy not being recommended based on race. Kaplan-Meier curves and log-rank tests were used to evaluate differences in overall survival. Propensity score methodology with inverse probability of treatment weighting (IPTW) was used to balance baseline differences in patient demographics. RESULTS: After IPTW adjustment, we identified 30 552 White patients and 3529 Black patients with clinical stage I-III esophageal carcinoma. Black patients had three times greater odds of not being recommended for esophagectomy (odds ratio: 3.03, 95% confidence interval: 2.67-3.43, p < 0.0001) compared to White patients. Black patients demonstrated significantly worse 3- and 5-year overall survival rates compared to White patients (log-rank p < 0.0001). CONCLUSION: Black patients with clinical stage I-III esophageal cancer were significantly less likely to be recommended for esophagectomy even after adjusting for baseline demographic covariates compared to White patients.

Circulating miR-21 as a potential biomarker in human digestive system carcinoma: a systematic review and diagnostic meta-analysis.

Purpose: Gastrointestinal cancers (GICs) account for about a quarter of cancers. Lately, the circulating microRNAs as a non-invasive biomarker for identifying and monitoring diseases have been recognized. Several studies have examined the role of miR-21 in digestive system carcinoma. We conducted a meta-analysis to assess the diagnostic role of miR-21 in GICs.Methods: Seventeen studies involving 1700 individuals were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, SROC, and Q* index were calculated based on true-positive, true-negative, false-negative, and false-positive. Moreover, the subgroup analyses have been performed for miR-21 based on sample types (serum/plasma), normalized genes (U6, miR-16, and miR-39), and ethnicity.Results: The pooled sensitivity 0.722 (95% CI: 0.70-0.74), specificity 0.820 (95% CI: 0.801-0.838), PLR 4.375 (95% CI: 3.226-5.933), NLR 0.308 (95% CI: 0.239-0.398), DOR 16.06 (95% CI: 9.732-26.53) as well as AUC 0.86, and Q* index 0.79 represented the high-grade diagnostic precision of miR-21 in identifying GICs (ESCC, GC, CRC, HCC, and PC).Conclusion: This meta-analysis demonstrated that circulating miR-21 levels can be used to monitor the digestive system carcinomas. Therefore, miR-21 can be a useful biomarker of progression and fair diagnosis in GICs patients.

Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage.

BACKGROUND & AIMS: African American and European American individuals have a similar prevalence of gastroesophageal reflux disease (GERD), yet esophageal adenocarcinoma (EAC) disproportionately affects European American individuals. We investigated whether the esophageal squamous mucosa of African American individuals has features that protect against GERD-induced damage, compared with European American individuals. METHODS: We performed transcriptional profile analysis of esophageal squamous mucosa tissues from 20 African American and 20 European American individuals (24 with no disease and 16 with Barrett's esophagus and/or EAC). We confirmed our findings in a cohort of 56 patients and analyzed DNA samples from patients to identify associated variants. Observations were validated using matched genomic sequence and expression data from lymphoblasts from the 1000 Genomes Project. A panel of esophageal samples from African American and European American subjects was used to confirm allele-related differences in protein levels. The esophageal squamous-derived cell line Het-1A and a rat esophagogastroduodenal anastomosis model for reflux-generated esophageal damage were used to investigate the effects of the DNA-damaging agent cumene-hydroperoxide (cum-OOH) and a chemopreventive cranberry proanthocyanidin (C-PAC) extract, respectively, on levels of protein and messenger RNA (mRNA). RESULTS: We found significantly higher levels of glutathione S-transferase theta 2 (GSTT2) mRNA in squamous mucosa from African American compared with European American individuals and associated these with variants within the GSTT2 locus in African American individuals. We confirmed that 2 previously identified genomic variants at the GSTT2 locus, a 37-kb deletion and a 17-bp promoter duplication, reduce expression of GSTT2 in tissues from European American individuals. The nonduplicated 17-bp promoter was more common in tissue samples from populations of African descendant. GSTT2 protected Het-1A esophageal squamous cells from cum-OOH-induced DNA damage. Addition of C-PAC increased GSTT2 expression in Het-1A cells incubated with cum-OOH and in rats with reflux-induced esophageal damage. C-PAC also reduced levels of DNA damage in reflux-exposed rat esophagi, as observed by reduced levels of phospho-H2A histone family member X. CONCLUSIONS: We found GSTT2 to protect esophageal squamous cells against DNA damage from genotoxic stress and that GSTT2 expression can be induced by C-PAC. Increased levels of GSTT2 in esophageal tissues of African American individuals might protect them from GERD-induced damage and contribute to the low incidence of EAC in this population.

Mucin expression in gastric- and gastro-oesophageal signet-ring cell cancer: results from a comprehensive literature review and a large cohort study of Caucasian and Asian gastric cancer.

BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Disparities in esophageal cancer: less treatment, less surgical resection, and poorer survival in disadvantaged patients.

The incidence of esophageal cancer has increased steadily in the last decades in the United States. The aim of this paper was to characterize disparities in esophageal cancer treatment in different racial and socioeconomic population groups and compare long-term survival among different treatment modalities. A retrospective analysis of the National Cancer Database was performed including adult patients (≥18 years old) with a diagnosis of resectable (stages I-III) esophageal cancer between 2004 and 2015. Multivariable logistic regression models were used to determine the odds of being offered no treatment at all and surgical treatment across race, primary insurance, travel distance, income, and education levels. Multivariable Cox proportional hazards models were used to compare 5-year survival rates across different treatment modalities. A total of 60,621 esophageal cancer patients were included. Black patients, uninsured patients, and patients living in areas with lower levels of education were more likely to be offered no treatment. Similarly, black race, female patients, nonprivately insured patients, and those living in areas with lower median residential income and lower education levels were associated with lower rates of surgery. Patients receiving surgical treatment, compared to both no treatment and definitive chemoradiation, had significant better long-term survival in stage I, II, and III esophageal cancer. In conclusion, underserved patients with esophageal cancer appear to have limited access to surgical care, and are, in fact, more likely to not be offered any treatment at all. Considering the survival benefits associated with surgical resection, greater public health efforts to reduce disparities in esophageal cancer are needed.

Lifestyle Risk Factors in Esophageal Cancer: An Integrative Review.

Esophageal cancer (EC) is a prevalent type of cancer, affecting more than 16 000 people annually in the United States. Being a high-burden disease, the comprehensive management of EC is challenging, particularly for older adults. In addition, Asian countries have some of the highest age-standardized incidence rates of EC in the world. Epidemiologic studies have revealed that cigarette and cigar smoking, alcohol drinking, obesity, being overweight, and areca chewing increase the risk of EC. This integrative review aims to elucidate the association between lifestyle factors such dietary habits, smoking, and alcohol consumption and EC among the Asian populations with Chinese, Japanese, and Taiwanese ethnicity. The synthesis of the literature found that environmental factors play an important role in the risk of EC occurrence. Although most of the risk factors showed a positive relationship in increasing the risk, studies included in this review reported inconclusive results on whether tea and coffee are risk factors. The consumption of very hot beverages and low intake of green vegetable are associated with EC. Smoking, alcohol intake, and their interaction with diets were found to be the biggest factor in the development of EC. Registered nurses can educate about esophageal thermal injury among persons who have preference for drinking burning-hot beverages and those with multiple risk factors, such as those who smoke and drink excess alcohol, as well as promoting health behaviors and serving as patient advocates.

[A new transition of the screening, early diagnosis and early treatment project of the upper gastrointestinal cancer: opportunistic screening].

The screening, early diagnosis and early treatment project of the upper gastrointestinal cancer had achieved good results since its launch. However, from a national perspective, the endoscopic screening of upper gastrointestinal cancer was still not optimistic, such as the poor rate of the early diagnosis, the low rate of 5-year survival in rural areas, and the disparity of the standardized screening and diagnosis in different areas. Therefore, the situation of upper gastrointestinal cancer prevention and treatment is still severe. Under the guidance of the "Healthy China 2030" plan, based on the international experience and domestic actual circumstance, it is suggested that the screening of high-risk population in high-risk areas should be changed into the opportunistic screening in primary medical institutions. The opportunistic screening could expand the coverage of the screening, early diagnosis and early treatment project of the upper gastrointestinal cancer, and increase the early diagnosis rate in rural areas and primary medical institutions, which could improve the 5-year survival rate of patients with the upper gastrointestinal cancer, and then achieve the sustainable development of the cancer prevention and treatment in China.

[Analysis of incidence and mortality of esophageal cancer in China, 2015].

Objective: To estimate the incidence and mortality rates of esophageal cancer in China in 2015. Methods: Based on the data quality review and assessment, the esophageal cancer data from 368 cancer registries in 31 provinces (autonomous regions and municipalities) in China were included in this study. According to the national population data in 2015, the nationwide incidence and mortality of the esophageal cancer were estimated. Chinese standard population in 2000 and world Segi's population were used to calculate the age-standardized (ASR) incidence and mortality rates (ASR China and world, respectively). Results: The 368 cancer registries covered a total of 309 553 499 populations in China, accounting for 22.52% of the national population. There were 245 651 new esophageal cancer cases estimated in China in 2015, with a crude incidence rate of 17.87/100 000. The ASR China and ASR world were 11.14/100 000 and 11.28/100 000, respectively. The estimated number of esophageal cancer death was 188 044 in China in 2015, with a crude mortality rate of 13.68/100 000; The ASR China and ASR world mortality rates were 8.33/100 000 and 8.36/100 000, respectively. The ASR China incidence and mortality of esophageal cancer in males were higher in males (16.50/100 000 and 12.66/100 000) than those in females (5.92/100 000 and 4.17/100 000), and they were higher in rural areas (15.95/1100 000 and 11.67/100 000) than those in urban areas (7.59/100 000 and 5.87/100 000). Conclusion: The incidence and mortality of esophageal cancer in China are higher than the global average. The disparity of the incidence and mortality rates of esophageal cancer significantly differed in genders and areas.

[Cost-effectiveness and cost-benefit analysis of upper gastrointestinal cancer screening in Yangzhong City, Jiangsu Province, from 2009 to 2015].

Objective: To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods: From 2009 to 2015, 31 natural villages with high-incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub-district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost-effectiveness analysis and cost-benefit analysis, were performed to evaluate the current screening schemes. Results: The mean age of all respondents were (53.60±8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high-grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness-cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions: The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

Endoscopy screening effect on stage distributions of esophageal cancer: A cluster randomized cohort study in China.

Efficacy of endoscopic screening for esophageal cancer is not sufficiently definitive and lacks randomized controlled trial evidence. The present study proved short-term screening efficacy through describing and comparing disease stage distributions of intervention and control populations. Villages from Linzhou and Cixian were cluster randomly allocated to the intervention or to the control group and the target population of 52 729 and 43 068 individuals was 40-69 years old, respectively, and the actual enrolled numbers were 18 316 and 21 178, respectively. TNM stage information and study-defined stage information of esophageal cases from 2012 to 2016 were collected. Stage distributions were compared between the intervention and control groups in the total target population, as well as in the subgroup populations in terms of enrolment and before or after intervention. There were a total of 199 and 141 esophageal cancer cases in the intervention and control groups, respectively. For the target population, distributions of TNM stage were borderline significant between the two groups after intervention (P = .093). However, subgroup analysis of the enrolled population during the after-intervention period had statistical significance for both TNM and study-defined stage. Natural TNM stage distributions were approximately 32%, 41%, 24% and 3% for stages I to IV vs 71%, 19%, 7% and 3% in the intervention population. The natural study-defined stage distributions from early, middle to advanced stages were approximately 18%, 49% and 33% vs 59%, 33% and 8%. Early-stage esophageal cancer cases accounted for a higher proportion after endoscopy screening, and the efficacy in the target population depends on the intervention compliance.

Survival Disparities by Race and Ethnicity in Early Esophageal Cancer.

BACKGROUND: Survival outcome disparities among esophageal cancer patients exist, but are not fully understood. AIMS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to determine whether survival differences among racial/ethnic patient populations persist after adjusting for demographic and clinical characteristics. METHODS: Our study included T1-3N0M0 adenocarcinoma and squamous cell cancer patients diagnosed between 2003 and 2011. We compared survival among two racial/ethnic patient subgroups using Cox proportional hazards methods, adjusting for age, sex, histology, marital status, socioeconomics, SEER region, comorbidities, T stage, tumor location, diagnosis year, and treatment received. RESULTS: Among 2025 patients, 87.9% were White and 12.1% were Nonwhite. Median survival was 18.7 months for Whites vs 13.8 months for Nonwhites (p = 0.01). In the unadjusted model, Nonwhite patients had higher risk of mortality (HR = 1.29, 95% CI 1.11-1.49, p < 0.0001) when compared to White patients; however, in the Cox regression adjusted model there was no significant difference (HR = 0.94, 95% CI 0.80-1.10, p = 0.44). Surgery, chemotherapy, younger age, lower T stage, and lower Charlson comorbidity score were significant predictors in the full adjusted model. CONCLUSIONS: Differences in mortality risk by race/ethnicity appear to be largely explained by additional factors. In particular, associations were seen in surgery and T stage. Further research is needed to understand potential mechanisms underlying the differences and to better target patients who can benefit from treatment options.

Hsa-miR-6743-5p Expression Varies with Lymph Node Metastasis in Esophageal Cancer.

BACKGROUND: Recently, esophageal cancer has become more common in China. To find a molecular biomarker will provide a handy way to improve precancerous diagnosis and evaluate the state of lymph node metastasis, improving prognosis. The present study aimed to investigate the expression level of hsa-miR-6743-5p in 25 esophageal tissues and to estimate the correlation between clinicopathological features of esophageal squamous cell cancer with miR-6743-5p expression. METHODS: Quantitative reverse transcription polymerase chain reaction was performed to examine the expression level of miR-6743-5p in 25 pairs of esophageal cancer tissues and adjacent non-cancerous tissues. The correlation between miR-6743-5p level and clinical characteristics was determined. RESULTS: The examined esophageal squamous cell cancer tissues exhibited no statistical difference on miR-6743-5p expression compared to the adjacent non-tumor tissues. miR-6743-5p was positively associated with lymph node metastasis. Downregulation of miR-6743-5p was found in the patients with lymph node metastasis while upregulation of miR-6743-5p was found in those without lymph node metastasis. CONCLUSIONS: Our study suggests that the expression of miR-6743-5p is different in different lymph node metastasis statuses. miR-6743-5p expression is downregulated in patients with lymph node metastasis in esophageal cancer.

Racial and Ethnic Disparities in the Incidence of Esophageal Cancer in the United States, 1992-2013.

Racial and ethnic disparities in the incidence of esophageal cancer have not been thoroughly characterized with quantitative health-disparity measures. Using data from 1992-2013 from 13 US cancer registries in the Surveillance, Epidemiology, and End Results database, we assessed such disparities according to histological type, based on a variety of disparity metrics. The age-standardized incidence rate of squamous cell carcinoma (SCC) was highest among black persons, while adenocarcinoma mainly affected white men. The rate of SCC decreased over time in all racial/ethnic groups, and this was most pronounced in black persons (by 5.7% per year among men and 5.0% among women). The adenocarcinoma rate rose among non-Hispanic whites and among black men. Racial/ethnic disparities in the incidence of total esophageal cancer decreased over time, which was due mainly to reduced disparities in SCC. The 2 absolute disparity measures-range difference and between-group variance-for adenocarcinoma rose by 3.2% and 6.8% per year, respectively, in men and by 1.8% and 5.3% per year, respectively, in women. This study demonstrates decreased racial/ethnic disparities in the incidence of esophageal SCC over time in the United States, while disparities increased in adenocarcinoma incidence as measured on the absolute scale.

Genomic Landscape of Esophageal Squamous Cell Carcinoma in a Japanese Population.

BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer in Japan. Smoking and drinking alcohol are environmental risk factors for ESCC, whereas single nucleotide polymorphisms in ADH1B and ALDH2, which increase harmful intermediates produced by drinking alcohol, are genetic risk factors. We conducted a large-scale genomic analysis of ESCCs from patients in Japan to determine the mutational landscape of this cancer. METHODS: We performed whole-exome sequence analysis of tumor and nontumor esophageal tissues collected from 144 patients with ESCC who underwent surgery at 5 hospitals in Japan. We also performed single-nucleotide polymorphism array-based copy number profile and germline genotype analyses of polymorphisms in ADH1B and ALDH2. Polymorphisms in CYP2A6, which increase harmful effects of smoking, were analyzed. Functions of TET2 mutants were evaluated in KYSE410 and HEK293FT cells. RESULTS: A high proportion of mutations in the 144 tumor samples were C to T substitution in CpG dinucleotides (called the CpG signature) and C to G/T substitutions with a flanking 5' thymine (called the APOBEC signature). Based on mutational signatures, patients were assigned to 3 groups, which associated with environmental (drinking and smoking) and genetic (polymorphisms in ALDH2 and CYP2A6) factors. Many tumors contained mutations in genes that regulate the cell cycle (TP53, CCND1, CDKN2A, FBXW7); epigenetic processes (MLL2, EP300, CREBBP, TET2); and the NOTCH (NOTCH1, NOTCH3), WNT (FAT1, YAP1, AJUBA) and receptor-tyrosine kinase-phosphoinositide 3-kinase signaling pathways (PIK3CA, EGFR, ERBB2). Mutations in EP300 and TET2 correlated with shorter survival times, and mutations in ZNF750 associated with an increased number of mutations of the APOBEC signature. Expression of mutant forms of TET2 did not increase cellular levels of 5-hydroxymethylcytosine in HEK293FT cells, whereas knockdown of TET2 increased the invasive activity of KYSE410 ESCC cells. Computational analyses associated the mutations in NFE2L2 we identified with transcriptional activation of its target genes. CONCLUSIONS: We associated environmental and genetic factors with base substitution patterns of somatic mutations and provide a registry of genes and pathways that are disrupted in ESCCs. These findings might be used to design specific treatments for patients with esophageal squamous cancers.

Racial Disparity in the Sex Distribution, the Prevalence, and the Incidence of Dysplasia in Barrett's Esophagus.

GOALS: Our aim was to study the prevalence of dysplasia and progression to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) in African Americans (AA) with Barrett's esophagus (BE) and compare it with that of non-Hispanic white (NHW) controls. BACKGROUND: BE, a precursor of EAC, is a disease of predominantly white men and is uncommon in AA. The prevalence of dysplasia and progression to HGD and EAC in AA patients with BE is not clearly known. STUDY: All AA or NHW patients with confirmed BE, that is specialized intestinal metaplasia, seen between 2002 and 2013 at our institution were included. Variables such as age, gender, medication use, the body mass index, the date of endoscopy, the hiatal hernia size, the BE length, and histologic findings were noted. Progression to HGD/EAC was evaluated. RESULTS: Fifty-two AA and 2394 NHW patients with BE were identified. There was a higher percentage of women in the AA cohort (46.2%) than in the NHW cohort (24.9%, P<0.001). Nondysplastic BE was more prevalent in AA than in NHW (80.8% vs. 68.4%, P=0.058). In the surveillance cohort of 20 AA and 991 NHW, no racial differences in progression to HGD/EAC were observed during a median follow-up of 43 months. CONCLUSIONS: This study includes the largest number of AA with histologically confirmed BE reported so far. About 46.2% of the AA cohort with BE in our study consisted of women. There was a trend toward a higher prevalence of nondysplastic BE in AA compared with NHW.

An age-period-cohort analysis of obesity and incident esophageal adenocarcinoma among white males.

The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades. Increases in incidence have been attributed to changes in the prevalence of risk factors for EAC; however, the extent to which these changes explain increases in EAC incidence has not been studied in detail. We used age-period-cohort analysis to estimate changes in the incidence of EAC among white males by age, time period, and birth cohort. Incidence rates per 100,000 individuals were analyzed from 1973 to 2012. Hierarchical Poisson models were used to estimate age, period, and cohort effects, whereby age-specific incidence rates were nested within periods and cohorts. The prevalence of obesity for each time period and birth cohort was included in the model as a fixed-effect. Incidence increased with advancing age (ß = 0.12, P < 0.01). There were significant period and birth cohort effects, although the period effect was much larger than the cohort effect. The period effect decreased dramatically when obesity was included as a fixed effect, while the small cohort effect remained unchanged. Results suggest much of the increase in the incidence of EAC can be attributed to a period effect, which may be due to changes in the prevalence of obesity over time.

Circulating miRNAs as novel potential biomarkers for esophageal squamous cell carcinoma diagnosis: a meta-analysis update.

Early detection of esophageal squamous cell carcinoma (ESCC) is urgently needed to reduce the high morbidity and mortality of disease. Circulating microRNAs (miRNAs) are promising molecular biomarkers for ESCC prediction. We performed a comprehensive meta-analysis to systematically evaluate the diagnostic accuracy of circulating miRNAs in diagnosis of ESCC patients. Eligible studies were identified and assessed for quality employing multiple search strategies. Summary estimates for sensitivity, specificity, and other measures of accuracy of miRNAs in the diagnosis of ESCC were pooled using the bivariate random effects model. A total of 27 studies from 11 published articles were included in the meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating miRNAs for the diagnosis of ESCC were 79.9% (95% confidence intervals [CI]: 76.2%-83.1%), 81.3% (95% CI: 75.7-85.9), 4.27 (95%CI: 3.27-5.58), 0.25 (95% CI: 0.21-0.29), and 17.29 (95% CI: 12.01-24.86), respectively. The area under the summary receiver operating characteristic curve was 0.87 (95% CI: 0.84-0.90). The subgroup analyses based on research country (China vs. Japan), specimen type (plasma vs. serum), miRNAs profiling (single vs. multiple), and test method (screening vs. candidate; Taqman vs. SYBR) indicated no significant difference in the diagnostic accuracy of each subgroup. Collectively, our findings indicate that circulating miRNAs have significant potential to be used as noninvasive biomarkers for early detection of ESCC. Moreover, the subgroup analyses demonstrated the feasibility of using blood miRNAs as an ESCC diagnostic biomarker in Japanese and Chinese populations. Further, both plasma and serum are recommended as clinical specimens for miRNA detection. Further studies will be needed to validate these findings using larger numbers of patients.

[Analysis of the incidence and age characteristics of upper gastrointestinal cancer among 2003-2012 in the high incidence area of esophageal cancer, Cixian County, in Hebei Province].

Objective: To investigate the overall incidence and age distribution of upper digestive tract cancer in Cixian county, and to provide a reliable basis of prevention and treatment for upper gastrointestinal cancer. Methods: Collected annual incidence rate among 2003-2012 from Cixian cancer registry and abstracted all incidence rate of upper digestive tract cancer. The age-standardized incidence rate by Chinese standard population (ASR China) was calculated using the national population composition of 2000. The age-standardized incidence rate by world standard population (ASR world) was calculated using the world population composition of 1964 of Segi's. The annual average change (APC) was used to estimate the growth rate of the last two years in comparision with the first two years, which was calculated by Joinpoint regression model. The data was divided into two sections (from 2003 to 2007, and from 2008 to 2012), and the rate difference of different age group was calculated. Results: The crude incidence rate of the digestive tract cancer from 2003 to 2012 was 165.36/100 000 (10 309/6 234 346), which dropped from 170.75/10 100 000 (1 029/602 638) of 2003 to 146.02/100 000 of 2012 (936/640 991).The PC and APC of the crude incidence rate of upper gastrointestinal cancer were-12.96%, and-1.54% (95%CI:-3.22%-0.07%), respectively. The PC and APC of ASR China were-10.83%, and-1.30% (95%CI: 2.54%-0.03%), respectively. The PC and APC of ASR world were-9.82%, and-1.13% (95%CI:-2.20%--0.03%), respectively. The incidence of upper gastrointestinal cancer decreased. The incidence rate of 2003-2007 and 2008-2012 were 171.55/100 000 (5 239/3 048 593), and 159.41/10 000 (5 070/3 180 514), respectively and the rate difference was-12.15/100 000. The decrease of rate difference of 70 to 74 years old was the most (-340.32/100 000) and the increase of rate difference over the age of 85 was the most (447.21/100 000). Conclusion: From 2003 to 2012, the crude incidence of upper digestive tract cancer in Cixian showed a decreasing trend, and the 70-74 years old age group shows the most obvious decline.