Protein tyrosine phosphatase nonreceptor 2:A New biomarker for digestive tract cancers

In this editorial,the roles of protein tyrosine phosphatase nonreceptor 2(PTPN2)in oncogenic transformation and tumor behavior and its potential as a therapeutic target in the context of gastrointestinal(GI)cancers are presented with respect to the article by Li et al published in ninth issue of the World Journal of Gastrointestinal Oncology.PTPN2 is a member of the protein tyrosine phosphatase family of signaling proteins that play crucial roles in the regulation of inflammation and immunity.Accordingly,early findings highlighted the contribution of PTPN2 to the pathogenesis of inflammatory and autoimmune disorders related to its dysfunction.On the other hand,recent studies have indicated that PTPN2 has many different roles in different cancer types,which is associated with the complexity of its regulatory network.PTPN2 dephosphorylates and inactivates EGFR,SRC family kinases,JAK1 and JAK3,and STAT1,STAT3,and STAT5 in cell type-and context-dependent manners,which indicates that PTPN2 can perform either prooncogenic or anti-oncogenic functions depending on the tumor subtype.While PTPN2 has been suggested as a potential therapeutic target in cancer treatment,to the best of ourknowledge,no clear treatment protocol has referred to PTPN2.Although there are only few studies that investigated PTPN2 expression in the GI system cancers,which is a potential limitation,the association of this protein with tumor behavior and the influence of PTPN2 on many therapy-related signaling pathways emphasize that PTPN2 could serve as a new molecular biomarker to predict tumor behavior and as a target for therapeutic intervention against GI cancers.In conclusion,more studies should be performed to better understand the prognostic and therapeutic potential of PTPN2 in GI tumors,especially in tumors resistant to therapy.

Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers

Resveratrol(RSV),the primary polyphenol found in grapes,has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines,including IL-1β,IL-6,IL-1ra and TNFα.Considering the close association between chronic inflammation and cancer development,RSV’s immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation,proliferation,neovascularization,and migration.Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress.In addition to immunomodulation,RSV inhibits cancer development by expressing anti-oxidant effects,causing cell cycle arrest,stimulating the function of certain enzymes,and activating cell signaling pathways.The end outcome is one of the various forms of cell death,including apoptosis,pyroptosis,necroptosis,and more,as it has been observed in vitro.RSV has been shown to act against cancer in practically every organ,while its effects on colon cancer have been documented more frequently.It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol.The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV,with a particular emphasis on cancers of the digestive tract,as a challenge for future clinical research that may contribute to the better prognosis of cancer.

HIF-1α-1790G>A polymorphism significantly increases the risk of digestive tract cancer:A meta-analysis

AIM:To investigate the association between hypoxiainducible factor-1α(HIF-1α) polymorphisms(-1772C>T and-1790G>A) and the risk of digestive tract cancer.METHODS:A total of 13 eligible studies were retrieved from Pub Med,EMBASE,and the ChinaNational Knowledge Infrastructure database.The odds ratios(ORs) and 95% confidence intervals(CIs) were calculated to estimate the strength of the associations.RESULTS:By pooling the eligible studies,we found that the HIF-1α-1772C>T polymorphism was not associated with the risk of developing digestive tract cancer(dominant comparison,OR:1.156; 95%CI:0.839-1.593; P heterogeneity = 0.007),and no significant association was found in the Asian population or the Caucasian population.However,for the-1790G>A polymorphism,carriers of the variant-1790 A allele had a significantly increased risk of digestive tract cancer compared with those with the wildtype-1790 G allele(dominant comparison,OR:3.252; 95%CI:1.661-6.368; P heterogeneity < 0.001).Additionally,this increased risk of digestive cancer was only detected in Asians; there was no significant association in Caucasians.CONCLUSION:This meta-analysis demonstrates that the HIF-1α-1790G>A polymorphism is associated with a significantly increased risk of digestive tract cancer,while the-1772C>T polymorphism is not.

RELATIONSHIP BETWEEN DRINKING WATER,VEGETABLES AND CANCER DEATH IN THE HIGH INCIDENCE AREA OF DIGESTIVE TRACT CANCER

The Paper analyzed of investigation datas on thedeath causes of digestive tract cancer in high-incidencearea between 70s and 80s. The results showed that thecancer-adjusted mortalities were 224.14/100000 and226.66/100000: it was 7 times as high as low-incidence(31.19/100000 and 29.82/100000). In 70s, the cancer deathof esophagus, stomach and liver (87.41/100000,73.93/100000 and 8.59/100000) were 28 times, 10 timesand 4 times as high as low-incidence area (3.70/100000,10.57/100000 and 1.94/100000), respectively (P<0.001). In80s, the cancer death of esophagus, stomach and liver(68.26/100000, 109.39/100000 and 23.89/100000) were 17times, 10 times and 4 times as high as low-incidence area(4.54/100000, 10.84/100000 and 6.35/100000), respectively(P<0.001). In high-incidence area, the cancer death ofesophagus was lower, of stomach and liver were higherin 80s than 70s, respectively (P<0.01)- The result alsoshowed that the nitrate content of drinking water andvegetables were 21.45mg/1 and 1185.27mg/kg in high-incidence area; it were significant higher than that in low-incidence area (2.14mg/1 and 41.6omg/kg), the nitritecontent (0.01mg/l) of drinking water in high-incidencearea was significant higher than that in low-incidencearea (0.004mg/l), but the nitrite content among vegetableswas no significant difference between the two regions(N0.05). Our results suggest that the nitrate and nitritecontents increase in drinking water and vegetables maybe an important risk factor of upper alimentary cancer inhigh-incidence area.

A study of the clinical characteristics in patients with digestive tract cancer related cognitive impairment

Objective:The aims of this study was to explore the clinical characteristics of patients with digestive tract cancer-related cognitive impairment(CRCI),and provide reference for the comprehensive clinical understanding,early prevention and treatment.Methods:164 patients with digestive tract cancer were divided into CRCI group and non-CRCI impairment group based on the Montreal Cognitive Assessment Scale(MOCA)and the Minimal Mental State Scale(MMSE).Baseline features,blood biochemical indexes,anxiety and depression were compared.Statistical analysis were carried out by SPSS software(version 20.0).Results:Among all the patients with CRCI,males were more common.Also,there were statistically differences in marital status,liver metastasis,hypertension,ferritin(FER),high density lipoprotein-cholesterol(HDL-C),low density lipoprotein-cholesterol(LDL-C),NK cells,anxiety and depression(P<0.05).Conclusion:Part of patients with digestive tract cancer have varied degrees of cognitive dysfunction.Marital status,hypertension,immune function,liver metastasis and serum lipid metabolism were the risk factors for patients with digestive tract CRCI.Early identification of CRCI is of great significance to ensure the integrity of treatment,improve the quality of life and prognosis for patients with digestive tract CRCI.

HER2 aberrations and heterogeneity in cancers of the digestive system: Implications for pathologists and gastroenterologists

Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.

Impact of comorbid anxiety and depression on quality of life and cellular immunity changes in patients with digestive tract cancers

AIM:A study was performed to investigate the impact of comorbid anxiety and depression (CAD) on quality of life (QOL) and cellular immunity changes in patients with digestive tract cancers. METHODS: One hundred and fifty-six cases of both sexes with cancers of the digestive tract admitted between March 2001 and February 2004 in the Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University were randomly enrolled in the study. Depressive and anxiety disorder diagnoses were assessed by using the Structured Clinical Interview for DSM-IV. All adult patients were evaluated with the Hamilton depressive scale (HAMD, the 24-item version), the Hamilton anxiety scale (HAMA, a modified 14-item version), quality of life questionnaire-core 30 (QLQ-C30), social support rating scale (SSRS), simple coping style questionnaire (SCSQ), and other questionnaires, respectively. In terms of HAMD ≥ 20 and HAMA ≥ 14, the patients were categorized, including CAD (n = 31) in group A, anxiety disorder (n = 23) in group B, depressive disorder (n = 37) in group C, and non-disorder (n = 65) in group D. Immunological parameters such as T-lymphocyte subsets and natural killer (NK) cell activities in peripheral blood were determined and compared among the four groups. RESULTS: The incidence of CAD was 21.15% in patients with digestive tract cancers. The average scores of social support was 43.67±7.05 for 156 cases, active coping 20.34±7.33, and passive coping 9.55±5.51. Compared with group D, subjective support was enhanced slightly in group A, but social support, objective support, and utilization of support reduced, especially utilization of support with significance (6.16 vs7.80, P<0.05); total scores of active coping decreased, while passive coping reversed; granulocytes proliferated, monocytes declined, and lymphocytes declined significantly (32.87 vs 34.00, P<0.05); moreover, the percentage of CD3, CD4, CD8 and CD56 in T lymphocyte subsets was in lower level, respectively, and CD56 showed a significant decline in group A (26.02 vs 32.20, P<0.05), however, CD4/CD8 ratio increased. Physical function, role function, fatigue, sleeplessness and constipation had significant changes among different groups by one-way ANOVA, and group A was in poor QOL. It revealed that global health-related quality of life (QL) were positively correlated with active coping and CD56; CAD was negatively correlated with QL, active coping and CD56. Furthermore, the step-wise regression analysis suggested that utilization of support, CD56, active coping, fatigue, sleeplessness and depression were significant factors contributing to QOL. CONCLUSION: CAD, which can impair QOL and cellular immunity, occurs with a higher incidence in patients with digestive tract cancers. Hence, it is essential to improve mental health for them with specifically tailored interventions.

Optimal choice of stapler and digestive tract reconstruction method after distal gastrectomy for gastric cancer:A prospective case–control study

BACKGROUND Gastric cancer is the most common cause of cancer-related deaths,and is classified according to its location in the proximal,middle,or distal stomach.Surgical resection is the primary approach for treating gastric cancer.This prospective study aimed to determine the best reconstruction method after distal gastrectomy for gastric cancer.AIM To explore the efficacy of different staplers and digestive tract reconstruction(DTR)methods after radical gastrectomy and their influence on prognosis.METHODS Eighty-seven patients who underwent radical gastrectomy for distal gastric cancer at our institution between April 2017 and April 2020 were included in this study,with a follow-up period of 12-26 mo.The patients were assigned to four groups based on the stapler and DTR plan as follows:BillrothⅠ(B-I)reconstruction+linear stapler group(group A,22 cases),B-I reconstruction+circular stapler group(group B,22 cases),Billroth II(B-II)reconstruction+linear stapler group(group C,22 cases),and B-II reconstruction+circular stapler group(group D,21 cases).The pathological parameters,postoperative gastrointestinal function recovery,postoperative complications,and quality of life(QOL)were compared among the four groups.RESULTS No significant differences in the maximum diameter of the gastric tumors,total number of lymph nodes dissected,drainage tube removal time,QLQ(QOL questionnaire)-C30 and QLQ-STO22 scores at 1 year postoperatively,and incidence of complications were observed among the four groups(P>0.05).However,groups A and C(linear stapler)had significantly lower intraoperative blood loss and significantly shorter anastomosis time,operation time,first fluid diet intake time,first exhaust time,and length of postoperative hospital stay(P<0.05)than groups B and D(circular stapler).CONCLUSION Linear staplers offer several advantages for postoperative recovery.B-I and B-II reconstruction methods had similar effects on QOL.The optimal solution can be selected according to individual conditions and postoperative convenience.

Prognostic Value of Sox2 Expression in Digestive Tract Cancers: A Meta-analysis

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang（up to October 2014）. A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers（esophageal, gastric, and colorectal cancers）. The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas（HR=1.55, 95% CI=1.04–2.31）, especially for patients with esophageal cancer（HR=2.04, 95%CI=1.30–3.22）, colorectal cancer（HR=1.40, 95% CI=1.04–1.89）, and digestive tract adenocarcinoma（HR=1.80, 95% CI=1.12–2.89）, for Europeans（HR=1.98, 95% CI=1.44–2.71） or patients who did not receive neoadjuvant treatment（HR=1.73, 95% CI=1.10–2.72）. Furthermore, Sox2 over-expression was highly correlated with vascular invasion（OR=1.86, 95% CI=1.25–2.77） and poor differentiation（OR=1.88, 95% CI=1.14–3.08）, especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.

A meta-analysis of caspase-8-652 6N del polymorphism and digestive tract cancer risk

Caspase-8(CASP8) is one key regulator of apoptosis of T lymphocytes and is encoded by the CASP8 gene. It has been reported that the six-nucleotide deletion polymorphism(-652 6 N del) of the CASP8 gene had effect on some cancer risk. Few studies explored the association between CASP8 gene polymorphism and digestive tract cancer risk.To evaluate the association between the CASP8-652 6 N del polymorphism and the risk of digestive tract cancer, we conducted this meta-analysis. We found that CASP8-652 6 N del polymorphism was associated with a significantly reduced risk of digestive tract cancer in the co-dominant model(del/del vs. ins/ins: OR= 0.82, 95%CI= 0.72-0.95;del/ins vs. ins/ins: OR = 0.92,95%CI = 0.87-0.97;dominant model(del/ins + del/del vs. ins/ins: OR = 0.91,95%CI =0.87-0.96, recessive model: del/del vs. del/ins + ins/ins: OR = 0.85, 95%CI = 0.75-0.97). In the stratified analysis by cancer types, we found that all genetic models had protective effect on gastric cancer. Similar results were observed for colorectal cancer under heterozygote comparison and dominant model, but not under homozygote comparison or recessive model. In addition, a significantly decreased risk was found on esophageal cancer for most genetic models,except heterozygote comparison. When stratified by ethnicity and source of control, an evidently decreased risk was identified in the Asian populations and population-based studies. In conclusion, there exists an association between the CASP8-652 6 N del polymorphism and reduced digestive cancer risk, especially among Asians and populationbased studies.

Tumor circulome in the liquid biopsies for digestive tract cancer diagnosis and prognosis

Digestive tract cancer is one of the main diseases that endanger human health.At present,the early diagnosis of digestive tract tumors mainly depends on serology,imaging,endoscopy,and so on.Although tissue specimens are the gold standard for cancer diagnosis,with the rapid development of precision medicine in cancer,the demand for dynamic monitoring of tumor molecular characteristics has increased.Liquid biopsy involves the collection of body fluids via noninvasive approaches,and analyzes biological markers such as circulating tumor cells,circulating tumor DNA,circulating cell-free DNA,microRNAs,and exosomes.In recent years,liquid biopsy has become more and more important in the diagnosis and prognosis of cancer in clinical practice due to its convenience,non-invasiveness,high specificity and it overcomes temporal-spatial heterogeneity.Therefore,this review summarizes the current evidence on liquid biopsies in digestive tract cancers in relation to diagnosis and prognosis.

Digestive tract reconstruction options after laparoscopic gastrectomy for gastric cancer

In addition to the popularity of laparoscopic gastrectomy(LG),many reconstructive procedures after LG have been reported.Surgical resection and lymphatic dissection determine long-term survival;however,the election of a reconstruction procedure determines the postoperative quality of life for patients with gastric cancer(GC).Presently,no consensus exists regarding the optimal reconstructive procedure.In this review,the current state of digestive tract reconstruction after LG is reviewed.According to the determining influence of the tumor site on the procedures of surgical resection and reconstruction,we divide these reconstruction procedures into three categories consistent with the resection procedures.We focus on the technical tips of every reconstruction procedure and examine the surgical outcomes(length of surgery and blood loss)and postoperative complications(anastomotic leakage and stricture)to facilitate gastrointestinal surgeons to understand the merits and demerits of every reconstruction procedure.

Digestive tract reconstruction pattern as a determining factor in postgastrectomy quality of life

Postgastrectomy quality of life (QoL) is affected by various symptoms, and compared with the preoperative baseline QoL, is typically impaired for the first 6 mo after surgery. Thereafter, improvement to a stable QoL is observed at approximately 12 mo postoperatively. We consider the digestive tract reconstruction pattern to be a determining factor in postgastrectomy QoL among gastric cancer patients, and believe it requires further discussion. Proximal gastrectomy is associated with the worst postoperative QoL among gastrectomy procedures and should be performed cautiously. The trend of better QoL provided by the pouch procedure of total gastrectomy requires further robust support. Whether the use of Billroth-I gastroduodenostomy or Roux-en-Y gastrojejunostomy for distal gastrectomy is optimal remains controversial, but Roux-en-Y gastrojejunostomy is likely to be preferable. (c) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer

Matrix metalloproteinases(MMPs) are implicated in cancer development and progression and are associated with prognosis.Single-nucleotide polymorphisms(SNPs) of MMPs,most frequently located in the promoter region of the genes,have been shown to influence cancer susceptibility and/or progression.SNPs of MMP-1,-2,-3,-7,-8,-9,-12,-13 and-21 and of the tissue inhibitor of metalloproteinases(TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors.The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.

Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome

BACKGROUND Lynch syndrome(LS)is a hereditary cancer predisposition syndrome associated with increased risk of multiple cancers.While colorectal cancer surveillance decreases mortality in LS and is recommended by guidelines,there is lack of evidence for the efficacy of surveillance for extra-colonic cancers associated with LS,including small intestinal cancer(SIC)and urinary tract cancer(UTC).Given the limited evidence,guidelines do not consistently recommend surveillance for SIC and UTC,and it remains unclear how often individuals will choose to undergo and follow through with extra-colonic surveillance recommendations.AIM To study factors associated with SIC and UTC surveillance uptake and outcomes in LS.METHODS This is an IRB-approved retrospective analysis of individuals with LS seen at a tertiary care referral center.Included individuals had a pathogenic or likely pathogenic variant in MLH1,MSH2,MSH6,PMS2,or EPCAM,or were a confirmed obligate carrier,and had at least one documented visit to our center.Information regarding SIC and UTC surveillance was captured for each individual,and detailed personal and family history was obtained for individuals who had an initial LS management visit in our center’s dedicated high-risk LS clinic between January 1,2017 and October 29,2020.During these initial management visits,all patients had in-depth discussions of SIC and UTC surveillance with 1 of 3 providers experienced in LS management to promote informed decision-making about whether to pursue SIC and/or UTC surveillance.Statistical analysis using Pearson’s chi-squared test and Wilcoxon rank-sum test was completed to understand the factors associated with pursuit and completion of SIC and UTC surveillance,and a P value below 0.05 was deemed statistically significant.RESULTS Of 317 individuals with LS,86(27%)underwent a total of 105 SIC surveillance examinations,with 5 leading to additional work-up and no SICs diagnosed.Additionally,99(31%)patients underwent a total of 303 UTC surveillance examinations,with 19 requiring further evaluation and 1 UTC identified.Of 155 individuals who had an initial LS management visit between January 1,2017 and October 29,2020,63(41%)chose to undergo SIC surveillance and 58(37%)chose to undergo UTC surveillance.However,only 26(41%)and 32(55%)of those who initially chose to undergo SIC or UTC surveillance,respectively,successfully completed their surveillance examinations.Individuals with a pathogenic variant in MSH2 or EPCAM were more likely to initially choose to undergo SIC surveillance(P=0.034),and older individuals were more likely to complete SIC surveillance(P=0.007).Choosing to pursue UTC surveillance was more frequent among older individuals(P=0.018),and females more frequently completed UTC surveillance(P=0.002).Personal history of cancer and family history of SIC or UTC were not significantly associated with electing nor completing surveillance.Lastly,the provider discussing SIC/UTC surveillance was significantly associated with subsequent surveillance choices.CONCLUSION Pursuing and completing SIC/UTC surveillance in LS is influenced by several factors,however broad incorporation in LS management is likely unhelpful due to low yield and frequent false positive results.

Role of microRNAs in the predisposition to gastrointestinal malignancies

MicroRNAs(miRNAs)are highly deregulated in cancer and play a role in the initiation of tumorigenesis.Recently,miRNAs have attracted attention in gastrointestinal(GI)cancers.Single nucleotide polymorphisms(SNPs)could affect the genes involved in each step of miRNA biosynthesis.Several metaanalyses of case-control studies have assessed the association between miRNA“pathway”gene-SNPs(including biosynthesis regulators and binding sites)and susceptibility to GI cancers.We present in this mini-review the current knowledge on the association between miRNAs“pathway”genes and GI cancer predisposition.The interaction between miRNA/regulators/binding site-SNPs and environmental as well as genomic factors is an interesting field that should be exploited in future studies.

Double Primary Cancers in Extragastric Sites with Gastric Cancer: Report of Six Cases and Literature Review

OBJECTIVE To explore the clinical features, pathologiccharacteristics and prognosis of double primary malignant tumorswith involvement of the stomach and an extragastric site.METHODS We reviewed the records of 496 patients whounderwent surgery for gastric cancer in our department fromJanuary 2004 to December 2006. Synchronous double primarycancer was defined as an extragastric cancer diagnosed within a6-month interval before the detection of gastric cancer; any gastriccancer metastasis to other areas of the body was excluded.RESULTS Synchronous and metachronous double primarycancers were identified in 1 and in 5 patients, respectively. Theextragastric sites of the primary tumors in patients with gastriccancer were esophagus in 1 case, right colon in 1, rectum in 1,breast in 2 and lung in 1. Following gastric surgery, 5 patientsdied (within 2 mon, 24 mon, 30 mon, 48 mon and 60 mon). Only 1patient has survived and remains disease free.CONCLUSION The prognosis of patients with gastric cancerand a second primary is relatively poor. It is necessary to performregular esophagogastroduodenoscopy (EGD) on patients whohave been diagnosed with extragastric cancer, regardless of theirsymptoms.

Role of Ubiquitin-Conjugating Enzyme UBE2C in Gastrointestinal Cancers

Ubiquitin-conjugating enzyme UBE2C is one of the important members of ubiquitin-proteasome pathway(UPP).Amplification and/or overexpression of UBE2C have been reported in many malignancies,and a high expression of UBE2C is associated with poor clinical outcomes.In this review,the pathological role of dysregulated UBE2C in gastrointestinal cancers and its potential role as a diagnostic and/or a prognostic marker as well as a therapeutic target in these cancers are discussed.

Role of narrow band imaging in endoscopic submucosal dissection

Narrow band imaging(NBI) is a new image enhancement system employing optic digital methods to enhance images of blood vessels on mucosal surfaces,allowing improved visualization of mucosal surface structures.Studies have progressed over the last several years,and the clinical usefulness has been demonstrated.NBI has become frequently applied for preoperative diagnosis before endoscopic submucosal dissection(ESD) of digestive tract cancers,as well as for assessment of the range of ESD for en-bloc resection of large lesions.Consensus has been reached with regard to the usefulness of NBI for detecting micro-lesions of esophageal squamous cell carcinoma indicated for ESD,for the diagnosis of the range and depth.NBI has also been attracting attention for diagnosing gastric cancer based on the observation of micro blood vessels on the mucosal surface and mucosal surface microstructures.The usefulness of NBI has been reported in relation to various aspects of colon cancer,including diagnoses of the presence,quality,range,and depth of lesions.However,as NBI has not surpassed diagnostic methods based on magnifying observation combined with the established and widely employed dye method,its role in ESD is limited at present.Although NBI is very useful for the diagnosis of digestive tract cancers,comprehensive endoscopic diagnosis employing the combination of conventional endoscopy including dye spraying,EUS,and NBI may be important and essential for ESD.

E2F transcription factors and digestive system malignancies:How much do we know?

The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell&#x02019;s fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current &#x02018;&#x02018;Letter to the Editor&#x02019;&#x02019;, we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.