Esophageal Cancer In China Research Articles

Neoadjuvant pembrolizumab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): Interim results.

e16011 Background: Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in China. Its prognosis remains poor and neoadjuvant treatment may improve the prognosis for resectable ESCC. The combination of immunotherapy with cytotoxic agents has shown encouraging antitumor activity in multiple tumors but data are lacking to support this approach as a neoadjuvant strategy for locally advanced ESCC. We conducted a prospective clinical trial of pre-operative pembrolizumab with chemotherapy in patients with locally advanced ESCC. Methods: Patients with clinical stage IIB-IVA ESCC eligible for resectable surgery were prospectively enrolled. Patients received neoadjuvant pembrolizumab (200mg) and chemotherapy (docetaxel 75mg/m2 plus cisplatin 75mg/m2 or carboplatin area under curve 4-5) every 3 weeks for four cycles before surgery. The primary endpoint was pathologic complete response (pCR) rate and radical (R0) resection rate. Secondary endpoints include Disease Free Survival (DFS), adverse events, and the correlation between biomarkers and immunotherapy efficacy. Results: From August 2020 to January 2022, 27 eligible patients participated the study. Twenty-four patients have completed four cycles of neoadjuvant therapy, among whom 22 patients were radiologically evaluable after neoadjuvant therapy. The objective response rate (ORR) was 68.2% and disease control rate was 100%. Among 22 patients with resectable tumors, 14 patients underwent McKeown MIE and 5 patients are still waiting for the surgery. Three other patients who achieved partial response (PR) refused surgery due to fear of complications. For 14 patients who underwent esophagectomy within 29-74 (median44) days after neoadjuvant treatment, all achieved radical resection. pCR (ypT0N0) was observed in 4 patients (4/14, 28.6%). Three patients (3/14,21.4%) had a College of American Pathologists (CAP) score of 1, one (1/14, 7.1%) had a CAP of 2, and 6 (6/14, 42.9%) had a CAP of 3. Most treatment-related AEs (TRAEs) were grade 1 or 2. Grade 3/4 TRAEs of leucopenia, decreased neutrophil count and dermatitis occurred in 9 (33.3%), 14 (51.9%), and 1 (3.7%) cases, respectively. No surgical complication was observed. Conclusions: Neoadjuvant pembrolizumab plus chemotherapy has achieved satisfactory initial efficacy and safety results in locally advanced ESCC. A phase III randomized controlled trial is required to confirm the clinical benefits of this neoadjuvant therapy.

Update and validation of a diagnostic model to identify prevalent malignant lesions in esophagus in general population

SummaryBackgroundPrevious risk prediction models taking esophageal malignant lesions detected during endoscopy as the primary outcome are not always sufficient to identify prevalent cases which are “overlooked” at screening. We aimed to update and externally validate our previous risk prediction model for malignant esophageal lesions by redefining the predicted outcome.Methods15,192 individuals from the Endoscopic Screening for Esophageal Cancer in China randomized controlled trial (ESECC trial, NCT01688908) were included as the training set, and 4576 participants from another population-based esophageal squamous cell carcinoma (ESCC) screening cohort (Anyang Esophageal Cancer Cohort Study, AECCS) served as the external validation set. Lesions with severe dysplasia or worse diagnosed at chromoendoscopy or identified via follow-up within 1 year after screening were defined as main outcome. Logistic regressions were applied to reconstruct the questionnaire-based prediction model using information collected before screening, with Akaike Information Criterion to determine the model structure.FindingsThe final prediction model included age and its quadratic term, family history of ESCC, low body mass index (≤22 kg/m2), use of coal or wood as main fuel for cooking, eating rapidly, and ingestion of leftover food. The area under the curve was 0·77 (95% CI: 0·73–0·80) and 0·71 (95% CI: 0·65–0·78) in the training and validation set. When screening the top 50% or 10% of high-risk individuals within population, the detection rates can be increased in both cohorts, as compared to universal screening.InterpretationThe described tool may promote the efficiency of current national screening programs for ESCC and contribute to a precision screening strategy in high-risk regions in China.FundingThis work was supported by the National Natural Science Foundation of China (82073626, 81773501), the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Key R&D Program of China (2021YFC2500405), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204) and the Beijing Nova Program (Z201100006820093). Sponsors had no role in the study design, data collection, analysis, and interpretation of data.

Relationship between postoperative complications of esophageal cancer surgery and season: a retrospective study

BackgroundEsophageal cancer in China accounts for nearly half of the global esophageal cancer cases. The relationship between the occurrence of postoperative complications of esophageal cancer surgery and seasonal changes is not clear. Our purpose is to clarify the relationship between postoperative complications of esophageal cancer and season, so as to reduce the incidence of complications.MethodsWe retrospectively analyzed the medical records of patients undergoing esophageal cancer surgery in our hospital between January 2013 and December 2014. Patients were divided into the summer group (March–August) and the non-summer group (September–February) according to the seasonal climate. Pulmonary, cardiac, and other complications were recorded. Differences in postoperative complications were compared between the two groups by the chi-squared test.ResultsIn the 251 patients enrolled, the total postoperative complication rate was 37.8%. The occurrence of incision complications in the summer group was significantly higher than that in the non-summer group (10.1% vs. 3.5%, P=0.044). Pulmonary and cardiac complications in summer group were significantly rarer than those in the non-summer group (16.7% vs. 27.4%, P=0.039; and 8.0% vs. 16.8%, P=0.032, respectively).ConclusionsDuring the warm months of the year, clinicians should focus on preventing postoperative incision complications, and they should focus on preventing pulmonary and cardiac complications during the cold months.

Roles of PTEN inactivation and PD-1/PD-L1 activation in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in China and developing countries. The purpose of this review is to summarize the roles of inactivation of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), and activation of the programmed cell death protein 1 (PD-1) upon binding to its ligand (PD-L1) in the promotion of ESCC. Studies of ESCC performed in vitro and in vivo indicated that PTEN and PD-L1 function in the regulation of cell proliferation, invasion, and migration; the epithelial-mesenchymal transition; resistance to chemotherapy and radiotherapy; and the PI3K/AKT signaling pathway. Certain genetic variants of PTEN are related to susceptibility to ESCC, and PTEN and PD-L1 also function in ESCC progression and affect the prognosis of patients with ESCC. There is also evidence that the expression of PD-L1 and PTEN are associated with the progression of certain other cancers. Future studies should further examine the relationship of PD-L1 and PTEN and their possible interactions in ESCC.

The Disease and Economic Burdens of Esophageal Cancer in China from 2013 to 2030: Dynamic Cohort Modeling Study.

BackgroundEsophageal cancer (EC) is the sixth leading cause of tumor-related deaths worldwide. Estimates of the EC burden are necessary and could offer evidence-based suggestions for local cancer control.ObjectiveThe aim of this study was to predict the disease burden of EC in China through the estimation of disability-adjusted life years (DALYs) and direct medical expenditure by sex from 2013 to 2030.MethodsA dynamic cohort Markov model was developed to simulate EC prevalence, DALYs, and direct medical expenditure by sex. Input data were collected from the China Statistical Yearbooks, Statistical Report of China Children’s Development, World Population Prospects 2019, and published papers. The JoinPoint Regression Program was used to calculate the average annual percentage change (AAPC) of DALY rates, whereas the average annual growth rate (AAGR) was applied to analyze the changing direct medical expenditure trend over time.ResultsFrom 2013 to 2030, the predicted EC prevalence is projected to increase from 61.0 to 64.5 per 100,000 people, with annual EC cases increasing by 11.5% (from 835,600 to 931,800). The DALYs will increase by 21.3% (from 30,034,000 to 36,444,000), and the years of life lost (YLL) will account for over 90% of the DALYs. The DALY rates per 100,000 people will increase from 219.2 to 252.3; however, there was a difference between sexes, with an increase from 302.9 to 384.3 in males and a decline from 131.2 to 115.9 in females. The AAPC was 0.8% (95% CI 0.8% to 0.9%), 1.4% (95% CI 1.3% to 1.5%), and –0.7% (95% CI –0.8% to –0.7%) for both sexes, males, and females, respectively. The direct medical expenditure will increase by 128.7% (from US $33.4 to US $76.4 billion), with an AAGR of 5.0%. The direct medical expenditure is 2-3 times higher in males than in females.ConclusionsEC still causes severe disease and economic burdens. YLL are responsible for the majority of DALYs, which highlights an urgent need to establish a beneficial policy to reduce the EC burden.

Gastric and esophageal cancer in China 2000 to 2030: Recent trends and short-term predictions of the future burden.

BackgroundGastric and esophageal cancer (GEC) have made a great contribution to the cancer burden in China. This study aims to report GEC incidence and mortality trends in 2000–2015 and their predictions to 2030.MethodsWe collected GEC data from 22 cancer registries for Joinpoint temporal trend analysis between 2000 and 2015 and average annual percent change was calculated. Based on the historical changes, combined with the 2015 GEC national incidence and mortality rate, the rate from 2016 to 2030 was predicted grouped by sex and age. The crude rate, standardized rate, and cumulative rate were calculated. The number of cases were obtained by multiplying the United Nations' World Population Prospects and the predicted rate of corresponding years. Attribution changes between 2015 and 2030 were apportioned into demographics and risk factors.ResultsThere were decreasing trends of age‐standardized incidence rate world (ASIRW) and age‐standardized mortality rate world (ASMRW) during 2000–2015 in China (p < 0.05), the decline was more significant for the age group of 40–49 years in men and the age group of 50–59 years in women. It was predicted that in 2030, about 549,724 new cases and 394,576 deaths of GEC would occur in China. Compared with 2015, the numbers of new GEC cases and deaths in 2030 decreased by 15.24% and 17.62%, respectively. From 2020 to 2030, GEC ASIRW and ASMRW were predicted to decline from 24.98 to 17.47 and from 17.41 to 11.82 per 100,000, respectively. The number of new cases decreased by about 15.24% with changing demographic (44.48%) and risk (−59.72%) and the number of deaths decreased by about 17.62% with changing demographic (47.18%) and risk (−64.80%).ConclusionsAlthough GEC incidence and mortality rates showed downward trends, the disease burden remains heavy in China. The current prevention and control strategy are effective which need to be carried on.

Association between XPD Lys751Gln polymorphism and esophageal cancer susceptibility in China: a meta-analysis based on 12 case-control studies

Abstract Many studies have analyzed the relation about xeroderma pigmentosum group D (XPD) Lys751Gln polymorphism on esophageal cancer risk; however, the results were inconclusive. The present study was designed to assess the relationship in China. We searched the relevant articles from the databases of PubMed, Springer Link, Ovid, Chinese Wanfang Database, CNKI and Chinese Biology Medicine up to December 2019. An OR with the corresponding 95%CI was adopted to evaluate this association. This meta-analysis included 12 studies with 4195 esophageal cancer cases and 4762 controls. Overall, a positive association between XPD Lys751Gln and esophageal cancer risk was found in all the analysis model (Gln vs. Lys, OR= 1.26, 95% CI= 1.14-1.44; Gln/Gln vs. Lys/Lys, OR= 1.73, 95% CI= 1.29-2.31; Gln/Gln vs. Lys/Lys + Asp/Asn, OR= 1.63, 95% CI= 1.22-2.18; Gln/Gln+ Asp/Asn vs. Lys/Lys, OR= 1.25, 95% CI= 1.13-1.39). Subgroup analyses by geographic area and source of controls were further conducted; there was no substantial change in subgroup analyses. Our study suggested that XPD Lys751Gln polymorphism could increase the risk of esophageal cancer in China. Further studies in other ethnic populations are wanted to confirm these conclusions.

The Incidence, Mortality, and DALYs Trends Associated with Esophageal Cancer - China, 1990-2019.

Esophageal cancer (EC) is one of the most common malignant tumors in China. The new cases and deaths in China account for more than half of the world, and the disease burden of esophageal cancer is serious. From 1990 to 2019, the disease burden of EC in China showed a decrease overall; it first increased between 1990 and 2004, but then decreased between 2004 and 2019. The burden of EC in men was much higher than that in women. Age was an important factor affecting the burden of EC, with disease burden rising rapidly after 40 years old. The screening, early diagnosis, and treatment for EC should continue to be strengthened in China. Middle-aged and elderly men are high-risk groups of EC and should be a key population for EC prevention and control.

Characteristics of Oral Microbiota in Patients with Esophageal Cancer in China.

Gut microbiota dysbiosis is closely associated with intestinal carcinogenesis, but the oral microbiota of patients with esophageal squamous cell carcinoma who live in high-risk regions in China has not been fully characterized. In the current study, oral microbial diversity was investigated in 33 patients with esophageal squamous cell carcinoma and 35 healthy controls in Chongqing, China, by sequencing 16S rRNA of V3-V4 gene regions. There were statistically significant differences in oral microbiota between esophageal squamous cell carcinoma patients and controls as determined via unweighted pair-group analysis with arithmetic means. At the phylum level, in esophageal squamous cell carcinoma patients, there were comparatively greater amounts of Firmicutes (34.0% vs. 31.1%) and Bacteroidetes (25.3% vs. 24.9%) and lower amounts of Proteobacteria (17.0% vs. 20.1%). At the genus level, esophageal squamous cell carcinoma patients exhibited comparatively greater amounts of Streptococcus (17.3% vs. 14.5%) and Prevotella_7 (8.6% vs. 8.5%) and lower amounts of Neisseria (8.1% vs. 10.7%). Using a linear discriminant analysis effect size method, Planctomycetes and Verrucomicrobia were identified in the esophageal squamous cell carcinoma group. 10 genera were higher abundances identified in the healthy control group, and different 10 genera were identified in the esophageal squamous cell carcinoma group. In the present study, there were significant differences in oral microbial compositions of esophageal squamous cell carcinoma patients and healthy controls. Further longitudinal and mechanistic studies are needed to further characterize relationships between oral microbiota and esophageal squamous cell carcinoma.

The association between depression and esophageal cancer in China: a multicentre population-based study

BackgroundEsophageal cancer (EC) is one of the leading contributors to the global burden of cancer, and the underlying mechanism is still unknown. Recently, there has been a growing interest in understanding modifiable psychosocial risk factors, particularly depression, to prevent EC and reduce morbidity and mortality. However, related research is sparse and has been ignored. The study was designed to assess the association between depression and EC in China.MethodsFrom 2017 to 2019, a population-based multicenter study was conducted in high-risk regions of EC. Participants underwent a free endoscopy screening. If the endoscopic results were suspicious, a pathological biopsy was applied to confirm. Depression was measured with Patient Health Questionnaire-9 (PHQ-9). In addition, information on demographic characteristics and risk factors was collected from participants by trained interviewers using uniform questionnaires.ResultsAfter Endoscopy and pathologic diagnosis, 15,936 participants in high-risk regions of EC (ECHRRs) were enrolled, 10,907 (68.44%) of which were diagnosed health, 4048 (25.40%) with esophagitis, 769 (4.83%) with low-grade intraepithelial neoplasia (LGIN), 157 (0.99%) with high-grade intraepithelial neoplasia (HGIN), and 55 (0.35%) with EC, respectively. The overall prevalence of depression symptoms of participants was 4.16% (health: 4.63%, esophagitis: 2.99%, LGIN: 2.99%, HGIN: 5.73%, and EC: 9.09%). Multiple logistic regression analyses revealed that the unadjusted OR (95% CI) between depression and each esophageal pathology grades were esophagitis 0.93 (0.92-0.95), LGIN 0.97 (0.94-0.99), HGIN 1.05 (1.00-1.10), and EC 1.04 (0.97-1.14), respectively. However, after adjustment for potential confounders (age, gender, region, alcohol consumption, BMI), no statistically significant associations between depression and EC (adjusted OR = 1.10, 0.99-1.21) and esophageal lesions (esophagitis: adjusted OR = 1.02, 0.99-1.04; LGIN: adjusted OR = 0.98, 0.95-1.01; HGIN: adjusted OR = 1.04, 0.98-1.11) were observed in this study.ConclusionsNo significant association was observed between depression and EC in the study. Future prospective cohort studies are needed to verify this preliminary finding.

Fusobacterium nucleatum predicts a high risk of metastasis for esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in ESCC tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinicopathologic characteristics of ESCC.ResultsMicroorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium (P = 0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage (P = 0.039) and clinical stage (P = 0.0039). The WES data showed that COL22A1, TRBV10–1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum-positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum-positive ESCC. Both a higher mutational burden and F. nucleatum-positive was observed in tumors with metastasis than in tumors without metastasis.ConclusionF. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a potential method to predict metastasis in ESCC.

Prediction of disease burden of esophageal cancer in China based on ARIMA and NNAR models

Objective To explore the time series characteristics of the disease burden of esophageal cancer in China and predict the disease burden of esophageal cancer. Methods The incidence, mortality, and disability adjusted life year (DALY) of esophageal cancer in China from 1990 to 2019 were collected. autoregressive integrated moving average (ARIMA) model and neural network autoregression (NNAR) model were established based on the data from 1990 to 2016, and model prediction performance was verified by comparing 2017-2019 forecast data with actual data through mean absolute percentage error (MAPE), modulation error ratio (MER), mean absolute error (MAE) and root mean squared error (RMSE). The better model was applied to predict the disease burden of esophageal cancer from 2020 to 2024. Results From 1990 to 2019, the overall disease burden of esophageal cancer in China showed a fluctuating upward trend, with the incidence rate rising by 33.26%, the mortality rate rising by 21.26%, and the DALY rate rising by 6.66%. The predicted values of disease burden by ARIMA model and NNAR model were basically consistent with the actual dynamic trend. The incidence rate of esophageal cancer in China from 2020 to 2024 would be 20.375/100 000, 21.057/100 000, 21.380/100 000, 21.341/100 000, 21.080/100 000, and mortality rate would be 18.834/100 000, 19.647/100 000, 20.407/100 000, 20.889/100 000, 20.988/100 000, and the DALY rate would be 418.192/100 000, 431.123/100 000, 442.780/100 000, 452.376/100 000, and 459.358/100 000. Conclusions The disease burden of esophageal cancer in China will increase slightly from 2020 to 2024. The NNAR model demonstrates good prediction performance and accuracy in simulating the disease burden of esophageal cancer in China, and provides a reference method for short-term prediction of the disease burden.

Epidemiological and clinical features of functional dyspepsia in a region with a high incidence of esophageal cancer in China.

Background:Functional dyspepsia (FD) has rarely been investigated in areas with a high prevalence of esophageal squamous cell carcinoma (ESCC). This study aims to reveal the epidemiological and clinical features of FD and organic dyspepsia (OD) in such a population.Methods:A middle-aged and elderly population-based study was conducted in a region with a high incidence of ESCC. All participants completed the Gastroesophageal Reflux Disease Questionnaire and Functional Gastrointestinal Disease Rome III Diagnostic Questionnaire, and they underwent gastroscopy. After exclusion of gastroesophageal reflux disease, uninvestigated dyspepsia (UID) was divided into OD and FD for further analyses.Results:A total of 2916 participants were enrolled from July 2013 to March 2014 in China. We detected 166 UID cases with questionnaires, in which 17 patients with OD and 149 with FD were diagnosed via gastroscopy. OD cases presented as reflux esophagitis (RE), ESCC, and duodenal ulcer. Heartburn (52.94%) and reflux (29.41%) were common in OD, but no symptomatic differences were found between FD and OD. Male sex, low education level, and liquid food were the risk factors for OD, while frequent fresh vegetable consumption was a protective factor. FD included 56 (37.58%) cases of postprandial distress syndrome (PDS), 52 (34.89%) of epigastric pain syndrome (EPS), nine (6.04%) of PDS + EPS, and 32 (21.48%) of FD + functional esophageal disorders. The Helicobacter pylori infection rate in FD patients was not higher than that in the control group (34.23% vs. 42.26%, P = 0.240). Frequent spicy food consumption was associated with PDS (odds ratio [OR]: 2.088, 95% confidence interval [CI]: 1.028–4.243), while consumption of deep well water was protective for PDS (OR: 0.431, 95% CI: 0.251–0.741).Conclusions:The prevalence of FD was 5.11% in the studied population. Gastroscopy should be prescribed for dyspepsia patients in case that ESCC and RE would be missed in UID cases diagnosed solely by the Rome III questionnaire.Trial Registration:ClinicalTrials.gov, NCT01688908; https://clinicaltrials.gov/ct2/show/record/NCT01688908.

PCN143 Real-World Assessment of the Treatment Patterns Associated with Un-Resectable Advanced and Metastatic Esophageal Cancer in China

To describe patient demographics, clinical status, treatment patterns, healthcare resource use (HCRU) and outcomes (clinical outcomes, disease recurrence, and cost) associated with unresectable advanced metastatic (UAM) esophageal cancer (EC) patients in China. This was a retrospective real-world observational study using an oncology database operated by Digital Health China (DHC), which is a comprehensive electronic health record (EHR) repository of patient demographics, clinical (including imaging, pathology.), medication use, HCRU, and cost data. Patients having ≥2 inpatient records with a primary ICD-10 code of EC were selected from Jan 1st, 2012 through Dec 31st, 2018. The first date of inpatient admission was defined as the index date. Patients were followed for a minimum ± 30 days from the index date. Demographics, clinical parameters, medication utilization, HCRU, and costs incurred were tracked for these cohorts. 5,948 patients met the inclusion/exclusion criteria, with 14.7% (n=873) with UAM EC. The mean age at index date of UAM EC patients was 61.4 (SD=9.0) years and 85.8% male. 52.9% of UAM EC patients had squamous cell carcinoma, and 1.6% had adenocarcinoma, with the remainder being unknown/other (45.5%). 83.2% (n=726) of UAM EC patients received first line (1L) chemotherapy; the most frequent being paclitaxel + cisplatin (25.9%, n=188). Of these 1L patients, 27.3% (n=198) went on to 2L treatment, where the most frequent treatment was also paclitaxel + cisplatin (6.1%, n=12). 20.7 % (n=41) of 2L patients received 3L treatment, where the most frequent treatment was fluorouracil + cisplatin (9.8%, n=4). The main adverse drug events due to treatment were gastrointestinal (32.5%) and myelosuppression (27.5%). In the post-index, 13.6% of UAM patients had loco-regional disease, whereas 68.8% had distant metastatic disease. 83.2% of patients with UAM EC received 1L treatment, with almost 70% of UAM EC patients having distant metastatic disease in the post-index.

Qigefang Inhibits Migration, Invasion, and Metastasis of ESCC by Inhibiting Gas6/Axl Signaling Pathway.

In recent years, there is an increasing interest in using Traditional Chinese Medicine (TCM) and their patents for the treatment of cancers. Qigefang (QGF) is a TCM formula and has been used for the treatment of metastatic esophageal cancer in China. However, its therapeutic effect on tumors and its mechanism of action is largely unknown. The aim of this study is to explore the role of QGF in the treatment of metastasis of Esophageal Squamous Cell Carcinoma( ESCC). Human esophageal carcinoma cell line KYSE150 was used for this study. CCK-8 assay was used to determine the cytotoxicity of QGF. The KYSE150 cells were treated with QGF to determine its effect on cell migration (cell scratch assay and imaging) and invasion (Transwell system based with Matrigel assay). Western blotting was used to investigate the effect of QGF on relevant molecules of signaling pathways. A mouse model of lung metastasis of esophageal cancer was established by injecting the KYSE150-Luc cells through the tail vein. A small animal imaging system was used to observe tumor metastasis in the mice. QGF reduced cell migration and invasion of KYSE150 cells. QGF significantly inhibited lung metastasis in nude mice. Further study revealed that the expression of Growth arrest-specific 6 (Gas6), Anexelekto (Axl), N-Nuclear factor-kappa B (NF-κB) and matrix metalloproteinase-9 (MMP-9) proteins were decreased both in vitro and in vivo upon treatment with QGF. QGF could prevent invasion and metastasis of esophageal cancer by inhibiting the Gas6/Axl signaling pathway.

Clinical Significance of Monitoring Circulating Free DNA and Plasma Heat Shock Protein 90alpha in Patients with Esophageal Squamous Cell Carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer in China and has an extremely poor prognosis. Circulating free DNA (cfDNA) and plasma heat shock protein 90alpha (Hsp90a) are two novel noninvasive biomarkers for diagnosis and prognostic prediction of several types of cancer. However, to the best of our knowledge, the roles of the two biomarkers in ESCC are still unknown.MethodsHere, we recruited 93 primary ESCC patients and detected plasma concentrations of the two markers at different time points, including 1–3 days pre-chemotherapy, 1–7 days pre-surgery and 7–14 days post-surgery. Baseline concentrations of the two markers were associated with main characteristics of ESCC patients which were collected at first diagnosis. Correlation between the two markers and traditional serum biomarkers at baseline was also examined. Furthermore, dynamic changes of the cfDNA and Hsp90α concentrations among different time points and the potential clinical significance were assessed.ResultsConsequently, there was no significant association between baseline concentrations of the two markers and clinical features. Especially, cfDNA demonstrated stronger correlation with other circulating biomarkers than Hsp90α at baseline level. Importantly, both cfDNA and Hsp90α concentrations were significantly increased after surgery. Kaplan–Meier survival analysis showed that a change in concentration of cfDNA (ΔcfDNA) but not Hsp90α (ΔHSP90ɑ) between pre-surgery and post-surgery had significant effect on the overall survival of surgical patients with ESCC.ConclusionThus, ΔcfDNA evaluation could be a promising prognostic marker for surgical ESCC patients. Our findings may improve the understanding of the function of cfDNA and Hsp90α in ESCC.

Correlates of Long-Term Survival of Patients with pN+ Esophageal Squamous Cell Carcinoma after Esophagectomy.

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. Patients with ESCC have poor long-term survival, especially those with lymphatic metastasis (pN + ESCC). In this retrospective study, we evaluated the correlates of long-term survival time of patients with pN + ESCC. A total of 453 patients with pN + ESCC who underwent surgical R0 resection between Jan 2008 and Sep 2011 were enrolled. The follow-up ended on December 2019. The clinical, pathological, inflammation-related factors and general survival data of these patients were analyzed using SPSS 22.0 software. The 1-, 3-, and 5-year overall survival (OS) rates were 73.7%, 34.6%, and 25.6%, respectively; the 1-, 3-, and 5-year disease-free survival (DFS) rates were 45.0%, 26.3%, and 20.4%, respectively. The median OS and DFS were 23 and 14 months, respectively. On multivariate analyses, gender, site of lesion, number of dissected lymph nodes, stage pTNM, adjuvant therapy, and neutrophil lymphocyte ratio were independent predictors of OS. Site of lesion, stage pTNM, and adjuvant therapy were independent predictors of DFS. Recursive partitioning analysis (RPA) scores of each patient were calculated based on the independent predictors of OS, and the patients were divided into 3 classes: low-risk, medium-risk, and high-risk. The OS, DFS, and local recurrence-free survival were significantly different among these three RPA classes (P < 0.001). Several factors showed an independent association with long-term postoperative survival of pN + ESCC patients after radical surgery. RPA scores can potentially be used to predict the prognosis of ESCC.

Esophageal cancer: trends in incidence and mortality in China from 2005 to 2015.

BackgroundThe long‐term trend analysis of esophageal cancer is rarely reported in China. Our purpose is to analyze the incidence and mortality trends of esophageal cancer in China from 2005 to 2015.MethodBased on the data in the annual report of the China Cancer Registry, a comprehensive analysis of esophageal cancer cases and deaths from 2005 to 2015 was carried out. The incidence and mortality of esophageal cancer are stratified by gender and region (urban or rural). Long‐term trend analysis was conducted using Joinpoint regression model.ResultIn China, the age‐standardized incidence rates by the world population declined from 13.84/105 in 2005 to 11.64/105 in 2015. Annual percent changes were 3.4% (95% CI: 0.6%, 6.3%) in the period 2005‐2011, −7.4% (95% CI: −10.1%, −4.7%) in the period 2011‐2015, respectively. The age‐standardized mortality rates declined from 10.86/105 in 2005 to 8.57/105 in 2015. And the average annual percent change was −4.1% (95% CI: −6.7%, −1.5%). The incidence and mortality of esophageal cancer in men are higher than those in women, and the incidence and mortality of esophageal cancer in rural areas are much higher than those in urban areas.ConclusionIn China, the incidence of esophageal cancer first increased and then decreased during 2005‐2015, while the mortality rate has been declining.

Changing trends in the disease burden of esophageal cancer in China from 1990 to 2017 and its predicted level in 25 years.

BackgroundNearly half of the cases of esophageal cancer in the world were in China, but the corresponding burden in China has not been estimated for the past decades or for the near future.MethodsData on the incidence, mortality, and disability‐adjusted life years (DALYs) rates owing to esophageal cancer in China from 1990 to 2017 were extracted from the Global Burden of Disease Study 2017. To reflect the trend in the disease burden, we calculated the estimated annual percentage change (EAPC) in the age‐standardized rates of these three outcomes in China from 1990 to 2017.ResultsThe age‐standardized incidence rate (ASIR) for esophageal cancer decreased from 19.38/100,000 in 1990 to 12.23/100,000 in 2017, with an EAPC of −2.53 (95%CI: −2.90, −2.16), but the number of cases of esophageal cancer increased from 164,473 to 234,624. The age‐standardized rates of esophageal cancer in females were always lower than they were in males during the study period, and there was a downward trend that was more pronounced among females than males. The most common risk factors for males were smoking and alcohol consumption, while the most common risk factors for females were a diet low in fruits and a high body mass index (BMI). New cases of, and deaths from esophageal cancer are predicted to increase by about 1.5 times in the coming 25 years.ConclusionAlthough the age‐standardized burden of esophageal cancer has been declining, the number of new cases of, and deaths from esophageal cancer have increased in China over the past 30 years, and they will continue to increase in the near future. Hence, national policies should be adopted to promote the prevention and management of known risk factors for it, especially smoking and excessive caloric intake.

Postoperative Adjuvant Therapy for Patients with pN+ Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. However, patient survival time after surgery remains unsatisfactory, especially in those who are pN+. This retrospective study determined the value of postoperative adjuvant therapy for patients with pN+ ESCC. From Jan 2008 to Sep 2011, 453 pN+ ESCC patients who underwent R0 resection and survived for at least 1 month were retrospectively enrolled. All patients received surgery. Some patients received surgery alone (SA, n = 131), and others received postoperative chemotherapy (POCT, n = 222), radiotherapy (PORT, n = 57), or sequential chemoradiotherapy (POCRT, n = 43). The follow-up ended on 1 Dec 2019. The 5-year overall survival (OS), disease-free survival (DFS), and locoregional recurrence (LR) were significantly worse in the SA group (15.2%, 13.1%, and 71.6%, all p < 0.05) than in the POCT group (28.0%, 20.8%, and 66.5%), the PORT group (27.4%, 24.4%, and 46.9%), and the POCRT group (42.8%, 35.5%, and 43.0%). Furthermore, compared with the SA group, the median OS and DFS were significantly longer in the POCT, PORT, and POCRT groups (all p < 0.05). PORT and POCRT (but not POCT) also significantly reduced the LR (p < 0.01). Multivariate Cox analysis showed that each type of postoperative therapy was independently associated with improvements in OS, DFS, and LR. Postoperative adjuvant therapy—either POCT, PORT, or POCRT—significantly improved OS and DFS in patients with pN+ ESCC after R0 surgery. PORT and PORCT significantly reduced LR in these patients.