MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is be-coming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer.

Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma

High-risk human papillomavirus has been suggested as a risk factor for esophageal adenocarcinoma.Tumor human papillomavirus status has been reported to confer a favorable prognosis in esophageal adenocarcinoma.The size of the primary tumor and degree of lymphatic spread determines the prognosis of esophageal carcinomas.Lymph node status has been found to be a predictor of recurrent disease as well as 5-year survival in esophageal malignancies.In human papillomavirus driven cancers,e.g.cervical,anogenital,head and neck cancers,associated lymph nodes with a high viral load suggest metastatic lymph node involvement.Thus,human papillomavirus could potentially be useful as a marker of micro-metastases.To date,there have been no reported studies regarding human papillomavirus involvement in lymph nodes of metastatic esophageal adenocarcinoma.This review highlights the importance of investigating human papillomavirus in lymph node metastasis of esophageal adenocarcinoma based on data derived from other human papillomavirus driven cancers.

Circulating exosomal miRNAs as potential biomarkers for Barrett's esophagus and esophageal adenocarcinoma

Exosomes,a class of extracellular vesicles,are small membrane-bound vesicles derived from almost all cell types that can play important roles in intercellular communication.Exosomes contain proteins,lipids,and nucleic acids that are obtained from the parental cells and participate in various pathophysiological processes,including cell growth,migration,inflammation,immune regulation,and tumor pathogenesis.Moreover,exosomes might be applied in clinical settings,such as diagnosis,treatment,and outcome prediction of diseases,including various cancers.The incidence rates of Barrett's esophagus(BE)and esophageal adenocarcinoma(EAC)have increased in recent decades,and studies have proposed specific factors that may contribute to the development and progression of these diseases.However,how exosomes play a role in this pathological process needs to be clarified.Studies have identified candidate microRNAs(miRNAs)that might be related to BE/EAC.Further studies are needed to ascertain whether circulating exosomal miRNAs are altered before or after disease onset,which could also help understand the pathophysiology of and find potential targets for prevention,diagnosis,and therapy in BE/EAC.This review summarizes recent findings on the features of circulating exosomal miRNAs in BE/EAC,which could be valuable for the early diagnosis,therapeutic approaches,and outcome prediction of BE/EAC.

Prognostic risk model construction and prognostic biomarkers identification in esophageal adenocarcinoma based on immune-related long noncoding RNA

Objective The aim of this study was to construct a prognostic model of esophageal adenocarcinoma(EAC)based on immune-related long noncoding RNAs(immune-related lncRNAs)and identify prognostic biomarkers using the Cancer Genome Atlas(TCGA)database.Methods Whole genomic mRNA expression and clinical data of esophageal adenocarcinoma were obtained from the TCGA database.The software Strawberry Perl,R and R packets were used to identify the immune-related genes and lncRNAs of esophageal adenocarcinoma,and for data processing and analysis.The differentially expressed lncRNAs were detected while comparing esophageal adenocarcinoma and normal tissue samples.The key immune-related lncRNAs were screened using lasso regression analysis and univariate cox regression analysis,and used to construct the prognostic model using multivariate cox regression analysis.To evaluate the accuracy of the risk prognostic model,all esophageal adenocarcinomas were divided into high-risk and low-risk groups according to the median risk score,after which Kaplan-Meier(K-M)survival curves,operating characteristic(ROC)curve and independent prognostic analysis of clinical traits were created.In addition,statistically significant immune-related lncRNAs and potential prognostic biomarkers were identified using the prognostic model and multifactor cox regression analysis for k-m survival analysis.Results A total of 1322 differentially expressed immune-related lncRNAs were identified,28 of which were associated with prognosis via univariate cox regression analysis.In addition,K-M survival analysis showed that the total survival time of the higher risk group was significantly shorter than that of the lower risk group(P=1.063e-10).The area under the ROC curve of 5-year total survival rate was 0.90.The risk score showed independent prognostic risk for esophageal adenocarcinoma via single factor and multifactorial independent prognostic analyses.In addition,the HR and 95%CI of each key immune-related lncRNA were calculated using multivariate Cox regression.Using k-m survival analysis,we found that 5 out of 12 key significant immune-related lncRNAs had independent prognostic value[AL136115.1(P=0.006),AC079684.1(P=0.008),AC07916394.1(P=0.0386),AC087620.1(P=0.041)and MIRLET7BHG(P=0.044)].Conclusion The present study successfully constructed a prognostic model of esophageal adenocarcinoma based on the TCGA database,with moderate predictive accuracy.The model consisted of the expression level of 12 immune-related lncRNAs.Furthermore,the study identified one favorable prognostic biomarker,MIRLET7BHG,and four poor prognostic biomarkers(AL136115.1,AC079684.1,AC016394.1,and AC087620.1).

Screening of prognostic genes associated with ferroptosis in esophageal adenocarcinoma and the establishment of its prognostic model

We analyzed three gene microarray datasets by GEO2R and obtained differential genes associated with ferroptosis in esophageal adenocarcinoma by obtaining the FerrDb database to obtain ferroptosis-related genes for the intersection.To further elaborate on the functions of differentially expressed genes(DGEs),this study performed gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis on DEGs.We used the Kaplan-Meier plotter database to verify the effect of DGEs genes on the overall survival of esophageal adenocarcinoma.We performed univariate/multifactorial COX regression analysis of DGEs genes associated with esophageal adenocarcinoma prognosis by R language to obtain ferroptosis-associated independent prognostic genes.To further understand the relationship between the upstream molecules of independent prognostic genes and ferroptosis,we obtained the upstream regulatory molecules miRNAs and LncRNAs of prognosis-related ferroptosis genes with the help of the miRWalk database,Oncomi database and StarBase database.we obtained a total of 75 DEGs.These DGEs were mainly enriched in the cellular response to lipids,and negative regulation of intracellular.These DGEs were mainly enriched in the negative regulation of intracellular signaling,positive regulation of cell death,cellular autophagy,HIF-1 signaling pathway,microRNAs in cancer,and ferroptosis.We performed prognostic analysis and univariate/multifactorial COX regression analysis on 75 ferroptosis-related genes and established four independent genes for esophageal adenocarcinoma,ATF3,ATM,ATG5,and HMGB1.The study also established hsa-miR-876-5p,hsa-miR-186-5p,hsa-miR-421,hsa-miR-505-3p,hsa-miR-503-5p,hsa-miR-299-3p and hsa-miR-191-5p,seven miRNAs with upstream regulation of LncRNAs.these miRNAs can be competitively bound by LncRNAs to prevent the inhibition of translation of target gene expression by miRNAs.In conclusion,our study identified four esophageal adenocarcinoma independent prognostic genes and their upstream regulatory molecules.These genes are involved in the ferroptosis regulation of cells and also play an important role in tumor therapy and drug resistance as one of the disease therapeutic targets.The study suggests that by targeting ATF3,ATM,ATG5,HMGB1 and their upstream regulatory molecules is a new direction for the treatment of esophageal adenocarcinoma.

Genomic Signature for the Prognosis of Survival in Relation to the Tumor Microenvironment in Esophageal Adenocarcinoma

Objective:To establish a new genomic signature for the prognosis of survival in relation to the tumor microenvironment in esophageal adenocarcinoma.Methods:Data from The Cancer Genome Atlas(TCGA)were applied,and the stromal and immune scores of patients with esophageal adenocarcinoma(EAC)were generated through the ESTIMATE algorithm.Differentially expressed genes were obtained,and genes concerning immune prognosis were identified on the basis of these scores.Functional analysis showed that these genes were primarily involved in immunobiological processes.Additionally,CIBERSORT was used to analyze 22 subgroups of tumor-infiltrating immune cells in the tumor microenvironment.Results:The results of the genomic assessment shown on the Kaplan-Meier curve revealed that EAC patients with high-risk scores have the worst survival.The risk score is valid as an independent prognostic factor for the overall survival in EAC patients.The tumor microenvironment was systematically analyzed,and the immune-related prognostic biomarkers of EAC have been proposed.Conclusion:The expression of tumor-infiltrating immune cells and immune-related genes in EAC have been identified.Some previously overlooked genes may be used as additional biomarkers for EAC in the future.

Transcription factor EHF interacting with coactivator AJUBA aggravates malignancy and acts as a therapeutic target for gastroesophageal adenocarcinoma

Transcriptional dysregulation of genes is a hallmark of tumors and can serve as targets for cancer drug development.However,it is extremely challenging to develop small-molecule inhibitors to target abnormally expressed transcription factors(TFs)except for the nuclear receptor family of TFs.Little is known about the interaction between TFs and transcription cofactors in gastroesophageal adenocarcinoma(GEA)or the therapeutic effects of targeting TF and transcription cofactor complexes.In this study,we found that ETS homologous factor(EHF)expression is promoted by a core transcriptional regulatory circuitry(CRC),specifically ELF3-KLF5-GATA6,and interference with its expression suppressed the malignant biological behavior of GEA cells.Importantly,we identified Ajuba LIM protein(AJUBA)as a new coactivator of EHF that cooperatively orchestrates transcriptional network activity in GEA.Furthermore,we identified KRAS signaling as a common pathway downstream of EHF and AJUBA.Applicably,dual targeting of EHF and AJUBA by lipid nanoparticles cooperatively attenuated the malignant biological behaviors of GEA in vitro and in vivo.In conclusion,EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS pathway.Targeting of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.

Overview of genetic and epigenetic alterations in the pathogenesis of esophagogastric junctional adenocarcinoma and esophageal adenocarcinoma: recent fi ndings by next generation sequencing

Esophagogastric junctional adenocarcinoma is commonly treated as esophageal adenocarcinoma(EAC)and has dramatically increased in Western countries for several decades.The similar trend has been observed in Asian countries(not in China).Barrett’s esophagus(BE)is a widely accepted precursor of EAC.Recent advances of next-generation sequencing could provide researchers with a better understanding of genetic and epigenetic alterations in the carcinogenesis of EAC.In this review,we have summarized the recently reported major genetic and epigenetic alterations in both BE and EAC.Sonic hedgehog/bone morphogenetic protein axis,which is a key signaling for esophageal development,plays an important role in BE intestinal metaplasia.Single nucleotide polymorphisms related to esophageal organogenesis,such as FOXF1 and FOXP3,are frequently detected in BE patients.During the progression of BE to adenocarcinoma,lacking of normal function of TP53 and CDKN2A by loss of heterozygosity(LOH),mutation,or promoter methylation has been frequently observed.LOH at 9p(coding CDKN2A)is an earlier event to EAC carcinogenesis compared to that at 17q(coding TP53)LOH.In order to further elucidate the pathogenesis of BE and EAC,it will be necessary to analyze these genetic/epigenetic alterations in combination with clinical data in a large-scale cohort.

Prediction of lymph node metastasis in early esophageal cancer

BACKGROUND Given the poor prognosis of patients with lymph node metastasis,estimating the lymph node status in patients with early esophageal cancer is crucial.Indicators that could be used to predict lymph node metastasis in early esophageal cancer have been reported in many recent studies,but no recent studies have included a review of this subject.AIM To review indicators predicting lymph node metastasis in early esophageal squamous cell carcinoma(ESCC)and early esophageal adenocarcinoma(EAC).METHODS We searched PubMed with“[early esophageal cancer(Title/Abstract)]and[lymph node(Title/Abstract)]”or“[early esophageal carcinoma(Title/Abstract)]and[lymph node(Title/Abstract)]”or“[superficial esophageal cancer(Title/Abstract)]and[lymph node(Title/Abstract)].”A total of 29 studies were eligible for analysis.RESULTS Preoperative imaging(size),serum markers(microRNA-218),postoperative pathology and immunohistochemical analysis(depth of invasion,tumor size,differentiation grade,lymphovascular invasion,neural invasion,expression of PIM-1<30%)were predictive factors for lymph node metastasis in both early ESCC and EAC.Serum markers(thymidine kinase 1≥3.38 pmol/L;cytokeratin 19 fragment antigen 21-1>3.30 ng/mL;stathmin-1)and postoperative pathology and immunohistochemical analysis(overexpression of cortactin,mixed-lineage leukaemia 2,and stanniocalcin-1)were predictive for lymph node metastasis in early ESCC.Transcription of CD69,myeloid differentiation protein 88 and toll-like receptor 4 and low expression of olfactomedin 4 were predictive of lymph node metastasis in early EAC.A total of 6 comprehensive models for early ESCC,including logistic regression model,nomogram,and artificial neural network(ANN),were reviewed.The areas under the receiver operating characteristic curve of these models reached 0.789-0.938,and the ANN performed best.As all these models relied on postoperative pathology,further models focusing on serum markers,imaging and immunohistochemical indicators are still needed.CONCLUSION Various factors were predictive of lymph node metastasis in early esophageal cancer,and present comprehensive models predicting lymph node metastasis in early ESCC mainly relied on postoperative pathology.Further studies focusing on serum markers,imaging and immunohistochemical indicators are still in need.

Clinical significance of signet ring cells in surgical esophageal and esophagogastric junction adenocarcinoma:A systematic review and meta-analysis

BACKGROUND The clinical significance of signet ring cells(SRCs)in surgical esophageal and esophagogastric junction adenocarcinoma(EEGJA)remains unclear now.AIM To explore the association between the presence of SRCs and the clinicopathological and prognostic characteristics in surgical EEGJA patients by combining and analyzing relevant studies.METHODS The PubMed,Web of Science,and EMBASE electronic databases were searched for the relevant literature up to March 28,2021.The relative risk(RR)with 95%confidence interval(CI)was calculated to assess the relationship between SRCs and clinicopathological parameters of surgical EEGJA patients,and the hazard ratio(HR)with 95%CI was calculated to explore the impact of SRC on the prognosis.All statistical analyses were conducted with STATA 12.0 software.RESULTS A total of ten articles were included,involving 30322 EEGJA patients.The pooled results indicated that the presence of SRCs was significantly associated with tumor location(RR:0.76,95%CI:0.61-0.96,P=0.022;I2=49.4%,P=0.160)and tumor-node-metastasis stage(RR:1.30,95%CI:1.02-1.65,P=0.031;I2=73.1%,P=0.002).Meanwhile,the presence of SRCs in surgical EEGJA patients predicted a poor overall survival(HR:1.36,95%CI:1.12-1.65,P=0.002;I2=85.7%,P<0.001)and disease-specific survival(HR:1.86,95%CI:1.55-2.25,P<0.001;I2=63.1%,P=0.043).CONCLUSION The presence of SRCs is related with advanced tumor stage and poor prognosis and could serve as a reliable and effective parameter for the prediction of postoperative survival and formulation of therapy strategy in EEGJA patients.However,more high-quality studies are still needed to verify the above findings.

Recent advances in multidisciplinary therapy for adenocarcinoma of the esophagus and esophagogastric junction

Esophageal adenocarcinoma(EAC)and adenocarcinoma of the esophagogastric junction(EGJA)have long been associated with poor prognosis.With changes in the spectrum of the disease caused by economic development and demographic changes,the incidence of EAC and EGJA continues to increase,making them worthy of more attention from clinicians.For a long time,surgery has been the mainstay treatment for EAC and EGJA.With advanced techniques,endoscopic therapy,radiotherapy,chemotherapy,and other treatment methods have been developed,providing additional treatment options for patients with EAC and EGJA.In recent decades,the emergence of multidisciplinary therapy(MDT)has enabled the comprehensive treatment of tumors and made the treatment more flexible and diversified,which is conducive to achieving standardized and individualized treatment of EAC and EGJA to obtain a better prognosis.This review discusses recent advances in EAC and EGJA treatment in the surgicalcentered MDT mode in recent years.

Role of endoscopic ultrasound in esophageal cancer

Esophageal cancer(ECA)affects 1 in 125 men and 1 in 417 for women and accounts for 2.6%of all cancer related deaths in the United States.The associated survival rate depends on the stage of the cancer at the time of diagnosis,making adequate work up and staging imperative.The 5-year survival rate for localized disease is 46.4%,regional disease is 25.6%,and distant/metastatic disease is 5.2%.Additionally,treatment is stage-dependent,making staging all that much important.For nonmetastatic transmural tumors(T3)and/or those that have locoregional lymph node involvement(N),neoadjuvant therapy is recommended.Conversely,for those who have earlier tumors,upfront surgical resection is reasonable.While positron emission tomography/computed tomography and other cross sectional imaging modalities are exceptional for detecting distant disease,they are inaccurate in staging locoregional disease.Endoscopic ultrasound(EUS)has played a key role in the locoregional(T and N)staging of newly diagnosed ECA and has an evolving role in restaging after neoadjuvant therapy.There is even data to support that the use of EUS facilitates proper triaging of patients and may ultimately save money by avoiding unnecessary or futile treatment.This manuscript will review the current role of EUS on staging and restaging of ECA.

Role of sirtuins in esophageal cancer:Current status and future prospects

Esophageal cancer(EC)is a malignant cancer that still has a poor prognosis,although its prognosis has been improving with the development of multidisciplinary treatment modalities such as surgery,chemotherapy and radiotherapy.Therefore,identifying specific molecular markers that can be served as biomarkers for the prognosis and treatment response of EC is highly desirable to aid in the personalization and improvement of the precision of medical treatment.Sirtuins are a family of nicotinamide adenine dinucleotide(NAD+)-dependent proteins consisting of seven members(SIRT1-7).These proteins have been reported to be involved in the regulation of a variety of biological functions including apoptosis,metabolism,stress response,senescence,differentiation and cell cycle progression.Given the variety of functions of sirtuins,they are speculated to be associated in some manner with cancer progression.However,while the role of sirtuins in cancer progression has been investigated over the past few years,their precise role remains difficult to characterize,as they have both cancer-promoting and cancer-suppressing properties,depending on the type of cancer.These conflicting characteristics make research into the nature of sirtuins all the more fascinating.However,the role of sirtuins in EC remains unclear due to the limited number of reports concerning sirtuins in EC.We herein review the current findings and future prospects of sirtuins in EC.

Esophagogastric junction adenocarcinoma:Preoperative chemoradiation or perioperative chemotherapy?

Multimodal treatment is currently the standard of care for locally advanced esophagogastric junction(EGJ)adenocarcinoma due to poor results after surgery alone.Neoadjuvant therapy is intended to shrink the tumor and eliminate potential circulating tumor cells.However,which neoadjuvant treatment is best for patients with EGJ tumors remains controversial.We aimed to compare outcomes of preoperative chemoradiation and perioperative chemotherapy for EGJ adenocarcinomas.For this purpose,we performed a thorough review of the literature describing neoadjuvant treatments for EGJ adenocarcinomas or comparing both therapies.Although some studies have shown better locoregional control and higher rates of complete pathologic response after chemoradiation,data suggest that both types of neoadjuvant therapy have similar survival benefits.As current data are heterogeneous and many studies have included significantly different types of patients in their analysis,future studies with better patient selection are still needed to define which neoadjuvant therapy should be chosen.In addition,targeted therapies and immunotherapy have promising results and should be further explored.

Clinical significance of molecular subtypes of gastrointestinal tract adenocarcinoma

Adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)represent a heterogeneous group of diseases with distinct etiology,clinical features,treatment approaches,and prognosis.Studies are ongoing to isolate molecular genetic subtypes,perform complete biological characterization of the tumor,determine prognostic groups,and find predictive markers to the effectiveness of therapy.Separate molecular genetic classifications were created for esophageal adenocarcinoma[The Cancer Genome Atlas(TCGA)],stomach cancer(TCGA,Asian Cancer Research Group),and colon cancer(Colorectal Cancer Subtyping Consortium).In 2018,isolation of TCGA molecular genetic subtypes for adenocarcinomas of the gastrointestinal tract(esophagus,stomach,and colon)highlighted the need for further studies and clinical validation of subtyping of gastrointestinal adenocarcinomas.However,this approach has limitations.The aim of our work was to critically analyze integration of molecular genetic subtyping of gastrointestinal adenocarcinomas in clinical practice.

Whole circumferential endoscopic submucosal dissection of superficial adenocarcinoma in long-segment Barrett's esophagus:A case report

BACKGROUND Esophageal adenocarcinoma(EAC)derived from long-segment Barrett’s esophagus(LSBE)is extremely rare in Asia.LSBE-related EAC is often difficult to diagnose in the horizontal extent.If the tumor has spread throughout the LSBE,whole circumferential endoscopic submucosal dissection(ESD)should be performed,which is difficult to complete safely.Additionally,whole circumferential ESD can bring refractory postoperative stenosis.We hereby report a case of EAC involving the whole circumference of the LSBE,achieving complete endoscopic removal without complications.CASE SUMMARY An 85-year-old man with the chief complaint of dysphagia underwent esophagogastroduodenoscopy.We suspected a flat-type cancerous lesion that extended the whole circumference of the LSBE(C 3.5,M 4.0)using narrow-band imaging magnification endoscopy(NBI-M).We achieved circumferential en bloc resection of the lesion safely with special ESD techniques.Histology of the ESD specimens demonstrated that the superficial EAC extended the whole circumference of the LSBE,and papillary or well-differentiated tubular adenocarcinoma was confined in the lamina propria mucosa showing a vertical negative margin.To prevent post-ESD stenosis,we performed endoscopic local injection of steroids,followed by oral administration of steroids.There was no evidence of esophageal refractory stenosis or tumor recurrence 30 mo after ESD.In summary,we experienced a rare case of LSBE-related EAC.The horizontal tumor extent was accurately diagnosed by NBI-M.Additionally,we achieve whole circumferential ESD safely without postoperative refractory stenosis.CONCLUSION NBI-M,ESD,and steroid therapy enabled the curative resection of superficial full circumferential LSBE-related EAC without refractory postoperative stenosis.

Cost-Utility Analysis of Nivolumab plus Chemotherapy in the First-Line Treatment of Upper Gastrointestinal Adenocarcinoma

Objective: To evaluate the cost-utility of nivolumab plus chemotherapy compared with chemotherapy alone as the first-line treatment for advanced gastric, gastro-oesophageal junction, and esophageal adenocarcinoma in China. Methods: Based on CheckMate649, a partitioned survival model was carried out with a circulation cycle of 6 weeks to simulate the patient’s lifetime. Sensitivity analysis were adopted to verify the robustness of the results. Results: The results of the base-case analysis showed that both the total cost and utility of the nivolumab group were higher, and the ICUR value was CNY 267498.67/QALY, more than 3 times the GDP per capita of China in 2020. The results of deterministic sensitivity analysis indicated that the three most influential factors were the utility value of PFS state, the cost of nivolumab and the discount rate. The results of probabilistic sensitivity analysis were consistent with those of base-case analysis, proving that the results were robust. The scenario analysis illustrated that economical price of nivolumab was CNY 3652.71. Conclusions: Under the willing-to-pay threshold of three times the GDP per capita of China in 2020, compared with chemotherapy alone, nivolumab plus chemotherapy is not a cost-effective option in China.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.

Comparative genomic analysis of esophageal squamous cell carcinoma and adenocarcinoma:New opportunities towards molecularly targeted therapy

Esophageal cancer is one of the most lethal cancers worldwide because of its rapid progression and poor prognosis.Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC)are two major subtypes of esophageal cancer.ESCC predominantly affects African and Asian populations,which is closely related to chronic smoking and alcohol consumption.EAC typically arises in Barrett’s esophagus with a predilection for Western countries.While surgical operation and chemoradiotherapy have been applied to combat this deadly cancer,molecularly targeted therapy is still at the early stages.With the development of large-scale next-generation sequencing,various genomic alterations in ESCC and EAC have been revealed and their potential roles in the initiation and progression of esophageal cancer have been studied.Potential therapeutic targets have been identified and novel approaches have been developed to combat esophageal cancer.In this review,we comprehensively analyze the genomic alterations in EAC and ESCC and summarize the potential role of the genetic alterations in the development of esophageal cancer.Progresses in the therapeutics based on the different tissue types and molecular signatures have also been reviewed and discussed.

Efficacy and safety of liquid nitrogen cryotherapy for treatment of Barrett's esophagus

AIM To evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE,with and without dysplasia,or intramucosal adenocarcinoma (IMC).METHODS This was a retrospective,single-center study carried out in a tertiary care center including 45 patients with BE who was treatment-na?ve or who had persistent intestinal metaplasia(IM),dysplasia,or IMC despite prior therapy.Barrett's mucosa was resected via EMR when clinically appropriate,then patients underwent cryotherapy until eradication or until deemed to have failed treatment.Surveillance biopsies were taken at standard intervals.RESULTS From 2010 through 2014,33 patients were studied regarding the efficacy of cryotherapy.Overall,29 patients (88%) responded to cryotherapy,with 84% having complete regression of all dysplasia and cancer.Complete eradication of cancer and dysplasia was seen in 75% of subjects with IMC; the remaining two subjects did not respond to cryotherapy.Following cryotherapy,15 patients with high-grade dysplasia (HGD) had 30% complete regression,50% IM,and 7% low-grade dysplasia (LGD); one subject had persistent HGD.Complete eradication of dysplasia occurred in all 5 patients with LGD.In 5 patients with IM,complete regression occurred in 4,and IM persisted in one.In 136 cryotherapy sessions amongst 45 patients,adverse events included chest pain (1%),stricture (4%),and one gastrointestinal bleed in a patient on dual antiplatelet therapy who had previously undergone EMR.CONCLUSION Cryotherapy is an efficacious and safe treatment modality for Barrett's esophagus with and without dysplasia or intramucosal adenocarcinoma.