Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Navigating the autophagic landscape:Epigenetic modulation in gastrointestinal cancer

This editorial comments on the manuscript by Chang et al,focusing on the still elusive interplay between epigenetic regulation and autophagy in gastrointestinal diseases,particularly cancer.Autophagy,essential for cellular homeostasis,exhibits diverse functions ranging from cell survival to death,and is particularly implicated in physiological gastrointestinal cell functions.However,its role in pathological backgrounds remains intricate and context-dependent.Studies underscore the dual nature of autophagy in cancer,where its early suppressive effects in early stages are juxtaposed with its later promotion,contributing to chemoresistance.This discrepancy is attributed to the dysregulation of autophagy-related genes and their intricate involvement in cellular processes.Epigenetic modifications and regulations of gene expression,including non-coding RNAs(ncRNAs),emerge as critical players in exerting regulatory control over autophagy flux,influencing treatment responses and tumor progression.Targeting epigenetic mechanisms and improving strategies involving the inhibition or induction of autophagy through pharmacological or genetic means present potential avenues to sensitize tumor cells to chemotherapy.Additionally,nanocarrier-based delivery of ncRNAs offers innovative therapeutic approaches.Understanding the intricate interaction between autophagy and ncRNA regula-tion opens avenues for the development of targeted therapies,thereby improving the prognosis of gastrointestinal malignancies with poor outcomes.

Early-onset gastrointestinal cancer:An epidemiological reality with great significance and implications

During the last few years,epidemiological data from many countries suggest that the incidence and prevalence of many cancers of the digestive system are shifting from the older to the younger ages,the so-called“early-onset cancer”.This is particularly evident in colorectal cancer and secondarily in other malignant digestive neoplasms,mainly stomach and in a lesser degree pancreas,and biliary tract.It should be emphasized that data concerning digestive neoplasms,except for those referring to the colon and stomach,could be characterized as rather insufficient.The exact magnitude of the shift in younger ages is expected to become clearer shortly,as long as relevant epidemiological data from many parts of the world would be available.The most important question concerns the etiology of this phenomenon,since its magnitude cannot be explained solely by the better diagnostic methodology and the preventive programs applied in many countries.The existing data support the assumption that a number of environ-mental factors may play a primary role in influencing carcinogenesis,sometimes from childhood.Changes that have appeared in the last decades related mainly to eating habits,consistency of gut microbiome and an increase of obese people interacting with genetic factors,ultimately favor the process of carcinogenesis.Even these factors however,are not entirely sufficient to explain the age-related changes in the frequency of digestive neoplasms.Studies of the individual effect of each of the already known factors or factors likely to be involved in the etiology of this phenomenon and studies using state-of-the-art technologies to accurately determine the degree of the population exposure to these factors are required.In this article,we attempt to describe the epidemiological data supporting the age-shifting of digestive malignancies and their possible pathogenesis.Finally,we propose some measures regarding the attitude of the scientific community to this alarming phenomenon.

Burden of gastrointestinal cancers among working-age population over past thirty years in China

BACKGROUND Although gastrointestinal(GI)cancers have been becoming a great public health concern in China,there is currently a lack of comprehensive literature on the overall burden and changing trends of GI cancers in the working-age population.AIM To assess the burden of GI cancers and to examine the overall,age-and genderspecific trends among the working-age population in China from 1990 to 2019.METHODS Data were extracted from the Global Burden of Disease Study 2019.The burden of GI cancers was indicated by incidence,mortality,disability-adjusted life-years(DALYs),age-standardized incidence rate(ASIR),age-standardized mortality rate,and age-standardized DALYs rate.Trends in the burden of GI cancers from 1990 to 2019 were examined using annual percent change and average annual percent change with Joinpoint regression models.RESULTS For overall GI cancers,a declining trend was observed in the ASIR,age-standardized mortality rate,and agestandardized DALYs rate,with reductions of 0.74%,2.23%,and 2.22%,respectively,from 1999 to 2019 in the Chinese working-age population.However,an increasing trend was observed in the ASIR for overall GI cancers from 2016-2019.The number of either incident cases,mortality cases,and DALYs was higher for colon/rectum cancer and liver cancer in younger participants but lower for esophageal,gallbladder,biliary tract,pancreatic,and stomach cancer among older subjects.Moreover,sex disparity in the GI cancers burden was also examined over 30 years.CONCLUSION The total burden of GI cancers remained heavy among the working-age population in China,although declining trends were observed from 1999 to 2019.Disparities in the GI cancers burden existed between sexes,age groups,and cancer types.Population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals,considering the age,sex,and cancer type disparities in China.

Impact of sleep on gastrointestinal cancer

Sleep problems have become a significant public health concern,affecting a large portion of the global population and have been linked to increased morbidity and mortality.The incidence of gastrointestinal(GI)cancers continues to rise,posing a substantial burden on healthcare systems worldwide.This editorial aims to delve into the impact of sleep on GI cancers,including esophageal,gastric,colorectal,hepatobiliary,and pancreatic cancer.Recent literature investigating the potential connections between GI cancers and sleep was reviewed.We considered aspects such as sleep duration,sleep disorders,and circadian rhythmicity,in order to explore the underlying mechanisms that can contribute to the development of GI cancers and propose avenues for future research.

Sine oculis homeobox homolog family function in gastrointestinal cancer:Progression and comprehensive analysis

The sine oculis homeobox homolog(SIX)family,a group of transcription factors characterized by a conserved DNA-binding homology domain,plays a critical role in orchestrating embryonic development and organogenesis across various organisms,including humans.Comprising six distinct members,from SIX1 to SIX6,each member contributes uniquely to the development and differentiation of diverse tissues and organs,underscoring the versatility of the SIX family.Dysregulation or mutations in SIX genes have been implicated in a spectrum of developmental disorders,as well as in tumor initiation and progression,highlighting their pivotal role in maintaining normal developmental trajectories and cellular functions.Efforts to target the transcriptional complex of the SIX gene family have emerged as a promising strategy to inhibit tumor development.While the development of inhibitors targeting this gene family is still in its early stages,the significant potential of such interventions holds promise for future therapeutic advances.Therefore,this review aimed to comprehensively explore the advancements in understanding the SIX family within gastrointestinal cancers,focusing on its critical role in normal organ development and its implications in gastrointestinal cancers,including gastric,pancreatic,colorectal cancer,and hepatocellular carcinomas.In conclusion,this review deepened the understanding of the functional roles of the SIX family and explored the potential of utilizing this gene family for the diagnosis,prognosis,and treatment of gastrointestinal cancers.

Organ and function preservation in gastrointestinal cancer: Current and future perspectives on endoscopic ablation

The escalating prevalence of gastrointestinal cancers underscores the urgency for transformative approaches.Current treatment costs amount to billions of dollars annually,combined with the risks and comorbidities associated with invasive surgery.This highlights the importance of less invasive alternatives with organ preservation being a central aspect of the treatment paradigm.The current standard of care typically involves neoadjuvant systemic therapy followed by surgical resection.There is a growing interest in organ preservation approaches by way of minimizing extensive surgical resections.Endoscopic ablation has proven to be useful in precursor lesions,as well as in palliative cases of unrese-ctable disease.More recently,there has been an increase in reports on the utility of adjunct endoscopic ablative techniques for downstaging disease as well as contributing to non-surgical complete clinical response.This expansive field within endoscopic oncology holds great potential for advancing patient care.By addressing challenges,fostering collaboration,and embracing technological advancements,the gastrointestinal cancer treatment paradigm can shift towards a more sustainable and patient-centric future emphasizing organ and function preservation.This editorial examines the evolving landscape of endoscopic ablation strategies,emphasizing their potential to improve patient outcomes.We briefly review current applications of endoscopic ablation in the esophagus,stomach,duodenum,pancreas,bile ducts,and colon.

Six transmembrane epithelial antigens of the prostate to illustrate inflammatory response in gastrointestinal cancers

Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe^(3+),Cu^(2+) reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

Receptor tyrosine kinase-like orphan receptor 1:A novel antitumor target in gastrointestinal cancers

Receptor tyrosine kinase-like orphan receptor 1(ROR1)is a member of the type I receptor tyrosine kinase family.ROR1 is pivotal in embryonic development and cancer,and serves as a biomarker and therapeutic target.It has soluble and membrane-bound subtypes,with the latter highly expressed in tumors.ROR1 is conserved throughout evolution and may play a role in the development of gastrointestinal cancer through multiple signaling pathways and molecular mechanisms.Studies suggest that overexpression of ROR1 may increase tumor invasiveness and metastasis.Additionally,ROR1 may regulate the cell cycle,stem cell characteristics,and interact with other signaling pathways to affect cancer progression.This review explores the structure,expression and role of ROR1 in the development of gastrointestinal cancers.It discusses current antitumor strategies,outlining challenges and prospects for treatment.

Role of molecular imaging in prognosis,diagnosis,and treatment of gastrointestinal cancers:An update on new therapeutic methods

One of the leading causes of cancer-related death is gastrointestinal cancer,which has a significant morbidity and mortality rate.Although preoperative risk assessment is essential for directing patient care,its biological behavior cannot be accurately predicted by conventional imaging investigations.Potential pathophysiological information in anatomical imaging that cannot be visually identified can now be converted into high-dimensional quantitative image features thanks to the developing discipline of molecular imaging.In order to enable molecular tissue profile in vivo,molecular imaging has most recently been utilized to phenotype the expression of single receptors and targets of biological therapy.It is expected that molecular imaging will become increasingly important in the near future,driven by the expanding range of biological therapies for cancer.With this live molecular fingerprinting,molecular imaging can be utilized to drive expression-tailored customized therapy.The technical aspects of molecular imaging are first briefly discussed in this review,followed by an examination of the most recent research on the diagnosis,prognosis,and potential future clinical methods of molecular imaging for GI tract malignancies.

Association of frailty and malnutrition with overall survival in adults with gastrointestinal cancer:A prospective cohort study

Background:Themortality burden of patients with gastrointestinalmalignancies is increasing worldwide,suggesting the need formore effective prognostic indicators.This study utilized a prospective cohort to(1)analyze the relationship between frailty and malnutrition and their association with the overall survival(OS)in adults with gastrointestinal cancer and(2)explore which specific frailty-related factors most significantly affect the OS.Methods:Participants diagnosed with gastrointestinal cancer from 2013 to 2018 who were enrolled in the Investigation on Nutrition Status and Clinical Outcome of Common Cancers study were identified.Malnutrition was determined using the Patient-Generated Subjective Global Assessment,whereas frailty was assessed using the FRAIL scale.The main outcome measured was the all-cause mortality.Multivariable-adjusted logistic regression was used to analyze the cross-sectional link between the nutritional status and frailty.Univariate and multivariate Cox regression analyses were conducted to explore the longitudinal association of these with the OS.Results:Among the 4,361 patients enrolled in the study,1,136 deaths were observed over a median follow-up of 43.4 months.Malnourished patients had a significantly higher risk of frailty than well-nourished patients(OR=6.25,95%CI=5.23–7.51).Frailty and malnutrition independently predicted the OS,with frailty showing an HR of 1.50(95%CI=1.33–1.69)and malnutrition showing an HR of 1.51(95%CI=1.31–1.74).Patientswith both frailty andmalnutrition had the highest all-causemortality risk(HR=1.82,95%CI=1.55–2.14)compared with patients with neither risk factor.Mortality rates rose with the accumulation of additional frailty-related factors.Conclusions:Malnutrition and frailty are interrelated prognostic factors in patients with gastrointestinalmalignancies,and their simultaneous presence worsens the patient outcomes.Higher scores for resistance and ambulation are major factors associated with a poorer outcome.Future large-scale prospective studies with repeated measurements are necessary to further explore the complex associations among frailty,malnutrition,and the prognosis in patients with gastrointestinal cancer.

Effect of music therapy on chemotherapy-induced nausea and vomiting in gastrointestinal cancer:A systematic review and metaanalysis

BACKGROUND Chemotherapy is the primary treatment for patients with advanced gastrointestinal cancer,but it has many adverse reactions,particularly nausea and vomiting.Music therapy can reduce anxiety symptoms,avoid the response to the human body under various stress conditions through psychological adjustment,and improve the adverse reactions of chemotherapy.AIM To investigate the impact of music therapy on relieving gastrointestinal adverse reactions in chemotherapy for patients with digestive tract cancer by metaanalysis.METHODS EMBASE,PubMed,OVID,WoS,CNKI,CBM,and VIP database were all used for searching relevant literature,and the efficacy after treatment was combined for analysis and evaluation.RESULTS This study included seven articles.The results of meta-analysis indicated that music therapy could reduce the nausea symptom score of patients after chemotherapy[mean difference(MD)=-3.15,95%confidence interval(CI):-4.62 to-1.68,Z=-4.20,P<0.0001].Music therapy could reduce the vomiting symptom score of patients after chemotherapy(MD=-2.28,95%CI:-2.46 to-2.11,Z=-25.15,P<0.0001).Furthermore,music therapy could minimize the incidence of grade I and above nausea or vomiting in patients after chemotherapy(odds ratio=0.38,95%CI:0.26-0.56,Z=-4.88,P<0.0001).Meta-regression analysis found that publication year was not a specific factor affecting the combined results.There was no significant publication bias(P>0.05).CONCLUSION Music therapy can significantly improve the scores of nausea and vomiting symptoms in patients with digestive system cancer during chemotherapy and reduce the incidence of grade I and above nausea and vomiting after chemotherapy,making it an effective psychological intervention method worthy of clinical promotion.

Roles of cancer stem cells in gastrointestinal cancers

Cancer stem cells(CSCs)are the main cause of tumor growth,invasion,metastasis and recurrence.Recently,CSCs have been extensively studied to identify CSCspecific surface markers as well as signaling pathways that play key roles in CSCs self-renewal.The involvement of CSCs in the pathogenesis of gastrointestinal(GI)cancers also highlights these cells as a priority target for therapy.The diagnosis,prognosis and treatment of GI cancer have always been a focus of attention.Therefore,the potential application of CSCs in GI cancers is receiving increasing attention.This review summarizes the role of CSCs in GI cancers,focusing on esophageal cancer,gastric cancer,liver cancer,colorectal cancer,and pancreatic cancer.In addition,we propose CSCs as potential targets and therapeutic strategies for the effective treatment of GI cancers,which may provide better guidance for clinical treatment of GI cancers.

Predictive value of frailty assessment tools in patients undergoingsurgery for gastrointestinal cancer: An observational cohort study

BACKGROUND Few studies have simultaneously compared the predictive value of various frailty assessment tools for outcome measures in patients undergoing gastrointestinal cancer surgery.Therefore,it is difficult to determine which assessment tool is most relevant to the prognosis of this population.AIM To investigate the predictive value of three frailty assessment tools for patient prognosis in patients undergoing gastrointestinal cancer surgery.METHODS This single-centre,observational,prospective cohort study was conducted at the Affiliated Lianyungang Hospital of Xuzhou Medical University from August 2021 to July 2022.A total of 229 patients aged≥18 years who underwent surgery for gastrointestinal cancer were included in this study.We collected baseline data on the participants and administered three scales to assess frailty:The comprehen-sive geriatric assessment(CGA),Fried phenotype and FRAIL scale.The outcome measures were the postoperative severe complications and increased hospital RESULTS The prevalence of frailty when assessed with the CGA was 65.9%,47.6%when assessed with the Fried phenotype,and 34.9%when assessed with the FRAIL scale.Using the CGA as a reference,kappa coefficients were 0.398 for the Fried phenotype and 0.291 for the FRAIL scale(both P<0.001).Postoperative severe complications and increased hospital costs were observed in 29(12.7%)and 57(24.9%)patients,respectively.Multivariate logistic analysis confirmed that the CGA was independently associated with increased hospital costs(odds ratio=2.298,95%confidence interval:1.044-5.057;P=0.039).None of the frailty assessment tools were associated with postoperative severe complications.CONCLUSION The CGA was an independent predictor of increased hospital costs in patients undergoing surgery for gastro-intestinal cancer.

Comprehensive analysis of cell-extracellular matrix protein Ras suppressor-1 in function and prognosis of gastrointestinal cancers

BACKGROUND Ras suppressor 1(RSU1),a highly conserved protein,plays an important role in actin cytoskeleton remodeling and cell-extracellular matrix adhesion.Aberration of RSU1 activity can cause changes in cell adhesion and migration,thereby enhancing tumor proliferation and metastasis.However,the correlation between RSU1 and gastrointestinal cancers(GICs),as well as its prognostic role related to tumor-infiltrating immune cells(TIICs)remains unclear.AIM To shows RSU1 plays a potential promoting role in facilitating tumor immune escape in GIC.METHODS Differential expression of RSU1 in different tumors and their corresponding normal tissues was evaluated by exploring the Gene Expression Profiling Interactive Analysis(GEPIA)dataset.The correlation between RSU1 expression and prognosis of GIC cancer patients was evaluated by Kaplan-Meier plotter.Then,RSU1-correlated genes were screened and functionally characterized via enrichment analysis.The correlation between RSU1 and TIICs was further characterized using the Tumor Immune Estimation Resource(TIMER).In addition,the correlation between RSU1 and immune cell surface molecules was also analyzed by TIMER.RESULTS High RSU1 expression was associated with poor overall survival of gastric cancer patients,exhibiting a hazard ratio(HR)=1.36,first progression HR=1.53,and post progression survival HR=1.6.Specifically,high RSU1 Levels were associated with prognosis of gastric cancer in females,T4 and N3 stages,and Her-2-negative subtypes.Regarding immune-infiltrating cells,RSU1 expression level was positively correlated with infiltration of CD4+T cells,macrophages,neutrophils,and dendritic cells(DCs)in colorectal adenocarcinoma and stomach adenocarcinoma.RSU1 expression was also predicted to be strongly correlated with immune marker sets in M2 macrophage,DCs and T cell exhaustion in GICs.CONCLUSION In gastrointestinal cancers,RSU1 is increased in tumor tissues,and predicts poor survival of patients.Increased RSU1 may be involved in promoting macrophage polarization,DC infiltration,and T cell exhaustion,inducing tumor immune escape and the development of tumors in GICs.We suggest that RSU1 is a promising prognostic biomarker reflecting immune infiltration level of GICs,as well as a potential therapeutic target for precision treatment through improving the immune response.

Clinical application of subjective global assessment in Chinese patients with gastrointestinal cancer

AIM： To investigate the role of subjective global assessment （SGA） in nutritional assessment and outcome prediction of Chinese patients with gastrointestinal cancer. METHODS： A total of 751 patients diagnosed with gastrointestinal cancer between August 2004 and August 2006 were enrolled in this study. Within 72 h after admission, SGA, anthropometric parameters, and laboratory tests were used to assess the nutritional status of each patient. The outcome variables including hospital stay, complications, and in-hospital medical expenditure were also obtained.RESULTS： Based on the results of SGA, 389 （51.8%）, 332 （44.2%）, and 30 （4.0%） patients were classified into well nourished group （SGA-A）, mildly to moderately malnourished group （SGA-B）, and severely malnourished group （SGA-C）, respectively. The prevalence of malnutrition classified by SGA, triceps skinfold thickness （TSF）, mid-upper arm muscle circumference （MAMC）, albumin （ALB）, prealbumin （PA）, and body mass index （BMI） was 48.2%, 39.4%, 37.7%, 31.3%, 21.7%, and 9.6%, respectively. In addition, ANOVA tests revealed significant differences in body mass index （BMI）, TSF, PA, and ALB of patients in different SGA groups. The more severely malnourished the patient was, the lower the levels of BMI, TSF, PA, and ALB were （P 〈 0.05）. x^2 tests showed a significant difference in SGA classification between patients receiving different types of treatment （surgery vs chemotherapy/radiotherapy）. As the nutritional status classified by SGA deteriorated, the patients stayed longer in hospital and their medical expenditures increased significantly. Furthermore, multiple regression analysis showed that SGA and serum ALB could help predict the medical expenditures and hospital stay of patients undergoing surgery. The occurrence of complications increased in parallel with the increasing grade of SGA, and was the highest in the SGA-C group （23.3%） and the lowest in the SGA-A group （16.8%）. CONCLUSION： SGA is a reliable assessment too and helps to predict the hospital stay and medica expenditures of Chinese surgical gastrointestina cancer patients.

Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer

AIM： To clarify alterations of Dickkopfs （Dkks） and Kremen2 （Krm2） in gastrointestinal cancer. METHODS： We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR, tissue microarray analysis, and methylation specific PCR （MSP）. Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor. WST-8 assays and/n y/tro invasion assays after treatment with specific siRNA for those genes were performed. RESULTS： Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues. This was correlated with promoter hypermethylation. There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer. In colorectal cancers with beta-catenin over-expression, Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without. Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION： Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.

Endoscopic submucosal dissection for premalignant lesions and noninvasive early gastrointestinal cancers

AIM: To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS: The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESDhad premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS: Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION: ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.

Evaluating efficacy of screening for upper gastrointestinal cancer in China:a study protocol for a randomized controlled trial

Objective： To evaluate the efficacy and feasibility of screening procedure for upper gastrointestinal cancer in both high-risk and non-high-risk areas in China. Setting： Seven cities/counties, representing three economical-geographical regions （Eastern, Central and Western） in China, were selected as screening centers： three in high-risk areas and four in non-high-risk areas. Participants： Villages/communities in these seven centers regarded as clusters were randomly assigned to either intervention group （screening by endoscopic examination） or control group （with normal community care） in a 1：1 ratio stratified by each center. Eligible participants are local residents aged 40-69 years in the selected villages/communities with no history of cancer or endoscopic examination in the latest 3 years who are mentally and physically competent. Those who are not willing to take endoscopic examination or are unwilling to sign the consent form are excluded from the study. Totally 140,000 participants will be enrolled. Interventions： In high-risk areas of upper gastrointestinal cancer, all subjects in screening group will be screened by endoscopy. In non-high-risk areas, 30% of the subjects in screening group, identified through a survey, will be screened by endoscopy. Primary and secondary outcome measures： The primary outcome is the mortality caused by upper gastrointestinal cancer. The secondary outcomes include detection rate, incidence rate, survival rate, and clinical stage distribution. Additional data on quality of life and cost-effectiveness will also be collected to answer important questions regarding screening effects. Conclusions： Screening strategy evaluated in those areas with positive findings may be promoted nationally and applied to the majority of Chinese people. On the other hand, negative findings will provide scientific evidence for abandoning a test and shifting resources elsewhere. Trial registration： The study has been registered with the Protocol Registration System in Chinese Clinical Trial Registry （identifier： ChiCTR-EOR-16008577）.