Nomograms and prognosis for superficial esophageal squamous cell carcinoma

In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

VEGF, HIF-1α, and Metabolic Indicators in Esophageal Squamous Cell Carcinoma

Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study

BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.

Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.

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.

Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

Clinical impact of surveillance for head and neck cancer in patients with esophageal squamous cell carcinoma

To evaluate the clinical impact of surveillance for head and neck (HN) region with narrow band imaging (NBI) in patients with esophageal squamous cell carcinoma (ESCC).METHODSSince 2006, we introduced the surveillance for HN region using NBI for all patients with ESCC before treatment, and each follow-up. The patients with newly diagnosed stage I to III ESCC were enrolled and classified into two groups as follows: Group A (no surveillance for HN region); between 1992 and 2000), and Group B (surveillance for HN region with NBI; between 2006 and 2008). We comparatively evaluated the detection rate of superficial head and neck squamous cell carcinoma (HNSCC), and the serious events due to metachronous advanced HNSCC during the follow-up.RESULTSA total 561 patients (group A: 254, group B: 307) were enrolled. Synchronous superficial HNSCC was detected in 1 patient (0.3%) in group A, and in 12 (3.9%) in group B (P = 0.008). During the follow up period, metachronous HNSCC were detected in 10 patients (3.9%) in group A and in 30 patients (9.8%) in group B (P = 0.008). All metachronous lesions in group B were early stage, and 26 patients underwent local resection, however, 6 of 10 patients (60%) in group A lost their laryngeal function and died with metachronous HNSCC.CONCLUSIONSurveillance for the HN region by using NBI endoscopy increase the detection rate of early HNSCC in patients with ESCC, and led to decrease serious events related to advanced metachronous HNSCC.

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in Xinjiang, China

AIM: To analyze the relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 andKazakh's esophageal squamous cell cancer in China.METHODS: The genotypes of cytochromes P450 (CYP) 2E1 and glutathione S-transferase (GST) M1 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) following PCR in 104 Kazakh's patients with esophageal cancer (EC) and 104 non-cancer controls.RESULTS: The frequency of CYP2E1 c1/c1 genotype was significantly higher in patients with cancer (77.9%) thanin control subjects (24.0%) (P＜0.05; OR, 11.13; 95%CI,5.84-21.22). The difference of GSTM1 null was significantly more frequent in the cancer (34.6%) vsthe control group (3.8%) (P＜0.05; OR, 13.24; 95%CI, 4.50-38.89). On the other hand, the combination of GSTM1 presence and CYP2E1 c1/c1 genotypes increased the risk for cancer (P＜0.05;OR, 13.42; 95%CI, 6.29-28.3).CONCLUSION: The CYP2E1 c1/c1, GSTM1 deletion genotypes are genetically susceptible biomarkers for ESCC in Kazakh population. Individuals with allele c1 of RsaI polymorphic locus for CYP2E1 may increase the risk of ESCC. Moreover, CYP2E1 wild type (c1/c1) increased thesusceptibility to ESCC risk in Kazakh individuals with GSTM1 presence genotype.

NEDD9 promotes cancer stemness by recruiting myeloid-derived suppressor cells via CXCL8 in esophageal squamous cell carcinoma

Objective:Esophageal squamous cell carcinoma(ESCC)has high morbidity and mortality rates worldwide.Cancer stem cells(CSCs)may cause tumor initiation,metastasis,and recurrence and are also responsible for chemotherapy and radiotherapy failures.Myeloid-derived suppressor cells(MDSCs),in contrast,are known to be involved in mediating immunosuppression.Here,we aimed to investigate the mechanisms of interaction of CSCs and MDSCs in the tumor microenvironment.Methods:ESCC tissues and cell lines were evaluated.Neural precursor cell expressed,developmentally downregulated 9(NEDD9)was knocked down and overexpressed by lentiviral transfection.Quantitative PCR,Western blot,immunohistochemistry,cell invasion,flow cytometry,cell sorting,multiplex chemokine profiling,and tumor growth analyses were performed.Results:Microarray analysis revealed 10 upregulated genes in esophageal CSCs.Only NEDD9 was upregulated in CSCs using the sphere-forming method.NEDD9 expression was correlated with tumor invasion(P=0.0218),differentiation(P=0.0153),and poor prognosis(P=0.0373).Additionally,NEDD9 was required to maintain the stem-like phenotype.Screening of chemokine expression in ESCC cells with NEDD9 overexpression and knockdown showed that NEDD9 regulated C-X-C motif chemokine ligand 8(CXCL8)expression via the ERK pathway.CXCL8 mediated the recruitment of MDSCs induced by NEDD9 in vitro and in vivo.MDSCs promoted the stemness of ESCC cells through NEDD9 via the Notch pathway.Conclusions:As a marker of ESCC,NEDD9 maintained the stemness of ESCC cells and regulated CXCL8 through the ERK pathway to recruit MDSCs into the tumor,suggesting NEDD9 as a therapeutic target and novel prognostic marker for ESCC.

EGFR expression as a predictive marker in esophageal squamous cell cancer:Review article

Esophageal cancer(EC)is a highly aggressive disease and 8thleading cause of death worldwide.Squamous cell cancer is the main histological type in China.Recent improvements in both surgical techniques and adjuvant/neoadjuvant radiotherapy and chemotherapy approaches have increased the survival of patients with the locoregional disease.However,most of the patients with EC have advanced disease either at diagnosis or at follow-up.Despite recent advances in the treatment,these patients still do poorly.Over expression of the epidermal growth factor receptor in esophageal cancer is associated with poor prognosis.However,very few researches have examined the role of epidermal growth factor receptor(EGFR)in prediction and therapeutic sensitivity to esophageal squamous cell cancer(ESCC).If pretherapeutic identification of esophageal squamous cell cancer which does not respond to chemoradiotherapy(CRT)can be done,it will help to improve the outcome of patients by selecting responders to treatment.In this review we describe the predictive significance of EGFR expression in ESCC.

A phase Ⅱ study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma

AIM:To evaluate the efficacy and safety of paclitaxelnedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma(ESCC).METHODS:A two-center,open-label,single-arm phaseⅡstudy was designed.Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events.Patients received 175mg/m2of paclitaxel over a 3 h infusion on 1 d,followed by nedaplatin 80 mg/m2in a 1 h infusion on 2 d every3 wk until the documented disease progression,unac-ceptable toxicity or patient’s refusal.RESULTS:Of the 36 patients assessable for efficacy,there were 2 patients(5.1%)with complete response and 16 patients(41.0%)with partial response,giving an overall response rate of 46.1%.The median progression-free survival and median overall survival for all patients were 7.1 mo(95%CI:4.6-9.7)and 12.4 mo(95%CI:9.5-15.3),respectively.Toxicities were moderate and manageable.Grade 3/4 toxicities included neutropenia(15.4%),nausea(10.3%),anemia(7.7%),thrombocytopenia(5.1%),vomiting(5.1%)and neutropenia fever(2.6%).CONCLUSION:The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.

Esophageal squamous cell carcinoma-precursor lesions and early diagnosis

Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis.Early detection is highly desirable,since surgical and endoscopic resection offers the only possible cure for esophageal cancer.Population screening should be undertaken in high risk areas,and in low or moderate risk areas for people with risk factors (alcoholics,smokers,mate drinkers,history of head and neck cancer,achalasia and lye stricture of the esophagus).Esophageal balloon cytology is an easy and inexpensive sampling technique,but the current methods are insufficient for primary screening due to sampling errors.Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection.It may be enhanced by several techniques such as dye and optic chromoendoscopy,magnifying endoscopy,and optical-based spectroscopic and imaging modalities.Since more than 80% of SCCE deaths occur in developing countries,where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable,the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy,since it is easy,accurate,inexpensive and available worldwide.In ideal conditions,or in developed countries,is it reasonable to think that optimal detection will require a combination of techniques,such as the combination of Lugol’s chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique.The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.

Short term results of endoscopic submucosal dissection in superficial esophageal squamous cell neoplasms

AIM: To evaluate the efficacy of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. METHODS: Between July 2007 and March 2009, 27 consecutive superficial esophageal squamous cell neoplasms in 25 enrolled patients were treated by endoscopic submucosal dissection. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The mean size of the lesions was 21 ± 13 mm (range 2-55 mm); the mean size of the resection specimens was 32 ± 12 mm (range 10-70 mm). The enblock resection rate was 100% (27/27), and en block resection with tumor-free lateral/basal margins was 88.9% (24/27). Perforation occurred in 1 patient who was managed by conservative medical treatments. None of the patients developed local recurrence or distant metastasis in the follow-up period. CONCLUSION: Endoscopic submucosal dissection is applicable to superficial esophageal squamous cell neoplasms with promising results.

Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line

Attrora-A kinase, a serine/threonine protein kinase, is a potential oncogene. Amplification and overexpression of Aurora-A have been found in several types of human tumors, including esophageal squamous cell carcinoma （ESCC）. It has been demonstrated that cells overexpressing Attrora-A are more resistant to cisplatin-induced apoptosis. However, the molecular mechanisms mediating these effects remain largely unknown. In this report, we showed that overexpression of Attrora-A through stable transfection of pEGFP-Aurora-A in human ESCC KYSE150 cells significantly promoted cell proliferation and inhibited cisplatin- or UV irradiation-induced apoptosis. Cleavages of caspase-3 and poly （ADPribose） polymerase （PARP） in Attrora-A overexpressing cells were substantially reduced after cisplatin or UV treatment. Furthermore, we found that silencing of endogenous Aurora-A kinase with siRNA substantially enhanced sensitivity to cisplatin- or UV-induced apoptosis in human ESCC EC9706 cells. In parallel, overexpression of Aurora-A potently upregulated the expression of Bcl-2. Moreover, the knockdown of Bcl-2 by siRNA abrogated the Aurora-A＇s effect on inhibiting apoptosis. Taken together, these data provide evidence that Aurora-A overexpression promoting cell proliferation and inhibiting apoptosis, suggesting a novel mechanism that is closely related to malignant phenotype and anti-cancer drugs resistance of ESCC cells.

Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

AIM To determine the association of p53, carcinoembryonic antigen(CEA) and CA19-9 protein expression with esophageal carcinogenesis.METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia(BCH), 247 with low-grade dysplasia(LGD), 51 with high-grade dysplasia(HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROCcurve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions.RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH.CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.

New magnifying endoscopic classification for superficial esophageal squamous cell carcinoma

To assess the accuracy of a new magnifying endoscopy (ME) classification for predicting depth of invasion of superficial esophageal squamous cell carcinoma (SESCC). METHODSThis study included a total of 70 lesions in 69 patients with SESCC who underwent ME with narrow-band imaging (ME-NBI) before resection from August 2010 to July 2016. Accuracy of ME-NBI for predicting depth of invasion of SESCC was analyzed by using a new ME classification proposed by the Japan Esophageal Society (JES), and interobserver agreement was assessed. RESULTSOverall accuracy of ME-NBI for estimating depth of invasion of SESCC was 78.6%. Sensitivity and specificity of type B1 for tumors limited to the epithelial layer (m1) or invading into the lamina propria (m2) were 71.4% and 100%, respectively. Sensitivity and specificity of type B2 for tumors invading into the muscularis mucosa (m3) or superficial submucosa (≤ 200 μm, sm1) were 94.4% and 73.1%, respectively, while those of type B3 for tumors invading into the deep submucosa (> 200 μm, sm2) were 75.0% and 97.8%, respectively. Interobserver agreement was excellent (κ = 0.86, 95%CI: 0.76-0.95). CONCLUSIONThe recently developed JES ME classification is useful for predicting depth of invasion of SESCC, with reliable interobserver agreement.

Clinicopathological parameters predicting recurrence of pT1N0 esophageal squamous cell carcinoma

AIM To identify the clinicopathological characteristics of pT1 N0 esophageal squamous cell carcinoma(ESCC) that are associated with tumor recurrence. METHODS We reviewed 216 pT1 N0 thoracic ESCC cases who underwent esophagectomy and thoracoabdominal two-field lymphadenectomy without preoperative chemoradiotherapy. After excluding those cases with clinical follow-up recorded fewer than 3 mo and those who died within 3 mo of surgery, we included 199 cases in the current analysis. Overall survival and recurrencefree survival were assessed by the Kaplan-Meier method, and clinicopathological characteristics associated with any recurrence or distant recurrence were evaluated using univariate and multivariate Cox proportional hazards models. Early recurrence(≤ 24 mo) and correlated parameters were assessed using univariate and multivariate logistic regression models.RESULTS Forty-seven(24%) patients had a recurrence at 3 to 178(median, 33) mo. The 5-year recurrence-free survival rate was 80.7%. None of 13 asymptomatic cases had a recurrence. Preoperative clinical symptoms, upper thoracic location, ulcerative or intraluminal mass macroscopic tumor type, tumor invasion depth level, basaloid histology, angiolymphatic invasion, tumor thickness, submucosal invasion thickness, diameter of the largest single tongue of invasion, and complete negative aberrant p53 expression were significantly related to tumor recurrence and/or recurrence-free survival. Upper thoracic tumor location, angiolymphatic invasion, and submucosal invasion thickness were independent predictors of tumor recurrence(Hazard ratios = 3.26, 3.42, and 2.06, P < 0.001, P < 0.001, and P = 0.002, respectively), and a nomogram for predicting recurrence-free survival with these three predictors was constructed. Upper thoracic tumor location and angiolymphatic invasion were independent predictors of distant recurrence. Upper thoracic tumor location, angiolymphatic invasion, submucosal invasion thickness, and diameter of the largest single tongue of invasion were independent predictors of early recurrence.CONCLUSION These results should be useful for designing optimal individual follow-up and therapy for patients with T1 N0 ESCC.

Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile

AIM： To examine the presence of human papillomavirus （HPV） in esophageal squamous cell carcinoma （ESCC） specimens collected from Colombia and Chile located in the northern and southern ends of the continent, respectively.METHODS： We examined 47 and 26 formalin-fixed and paraffin-embedded ESCC specimens from Colombia and Chile, respectively. HPV was detected using GP5＋/GP6＋ primer pair for PCR, and confirmed by Southern blot analysis. Sequencing analysis of L1 region fragment was used to identify HPV genotype. In addition, P16^INK4A protein immunostaining of all the specimens was conducted.RESULTS： HPV was detected in 21 ESCC specimens （29%）. Sequencing analysis of L1 region fragment identified HPV-16 genome in 6 Colombian cases （13%） and in 5 Chilean cases （19%）. HPV-18 was detected in i0 cases （21%） in Colombia but not in any Chilean case. Since Chilean ESCC cases had a higher prevalence of HPV-16 （without statistical significance）, but a significantly lower prevalence of HPV-18 than in Colombian cases （P = 0.011） even though the two countries have similar ESCC incidence rates, the frequency of HPV-related ESCC may not be strongly affected by risk factors affecting the incidence of ESCC. HPV-16 genome was more frequently detected in p16 positive carcinomas, although the difference was not statistically significant. HPV-18 detection rate did not show any association with p16 expression. Well-differentiated tumors tended to have either HPV-16 or HPV-18 but the association was not statistically significant. HPV genotypes other than HPV-16 or 18 were not detected in either country.CONCLUSION： HPV-16 and HPV-18 genotypes can be found in ESCC specimens collected from two South American countries. Further studies on the relationship between HPV-16 presence and p16 expression in ESCC would aid understanding of the mechanism underlying the presence of HPV in ESCC.

No evidence of HPV DNA in esophageal squamous cell carcinoma in a population of Southern Brazil

AIM:To investigate the association between human papillomavirus(HPV)and esophageal squamous cell carcinoma(ESCC)in southern Brazil.METHODS:We studied 189 esophageal samples from125 patients from three different groups:(1)102 biopsies from 51 patients with ESCC,with one sample from the tumor and another from normal esophageal mucosa distant from the tumor;(2)50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma(HNSCC);and(3)37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients,not exposed to smoking or alcohol consumption.Nested-polymerase chain reaction(PCR)with the MY09/11 and GP5/6 L1primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks.All PCR reactions were performed with a positive control(cervicovaginal samples),with a negative control(Human Genomic DNA)and with a blank reaction containing all reagents except DNA.We took extreme care to prevent DNA contamination in sample collection,processing,and testing.RESULTS:The histological biopsies confirmed the diagnosis of ESCC in 52 samples(51 from ESCC group and 1 from the HNSCC group)and classified as well differentiated(12/52,23.1%),moderately differentiated(27/52,51.9%)or poorly differentiated(7/52,13.5%).One hundred twenty-eight esophageal biopsies were considered normal(51 from the ESCC group,42 from the HNSCC group and 35 from dyspeptic patients).Nine had esophagitis(7 from the HNSCC and 2 from dyspeptic patients).Of a total of 189 samples,only 6 samples had insufficient material for PCR analysis:1 from mucosa distant from the tumor in a patient with ESCC,3from patients with HNSCC and 2 from patients without cancer.In 183 samples(96.8%)GAPDH,G3PDH and/orβ-globin were amplified,thus indicating the adequacy of the DNA in those samples.HPV DNA was negative in all the 183 samples tested:52 with ESCC,9 with esophagitis and 122 with normal esophageal mucosa.CONCLUSION:There was no evidence of HPV infection in different ESCC from southern Brazil.