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.

Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population

AIM: To investigate the relation of human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC)in Iranian patients as compared to normal controls.METHODS: Using MY09/MY11 consensus primers, we compared the prevalence of a HPV L1 gene in tumor tissues from 38 ESCC cases and biopsied tissues from 38endoscopically normal Iranian individuals. We also compared the presence of HPV16 and HPV18 in the same samples using type-specific E6/E7 primers.RESULTS: Fourteen (36.8%) of the 38 ESCC samples but only 5 (13.2%) of the 38 control samples were positive for the HPV L1 gene (P = 0.02). Five (13.2%) of the ESCC samples but none of the control samples were positive for the HPV16 E6/E7gene (P = 0.05). Three (7.9%) of the ESCC samples and 5 (13.2%) of the control samples were positive for the HPV18 E6/E7gene (P = 0.71).CONCLUSION: Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor contributing to the high incidence of ESCC in Iran and other high-incidence areas of the world.

Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

Basaloid squamous cell carcinoma (BSC) of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC,who was successfully treated by systemic chemotherapy containing 5-fluorouracil (5-FU) and cisplatin (CDDP). A 57-year-old woman was diagnosed as having squamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC. Five months after operation,the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen,and a right paraclavicular lymph node. She was given systemic chemotherapy consisting of continuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared,and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses,with progression afterwards. Although subsequent treatment with CPT-11 and CDDP was not effective,docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.

Squamous Cell Carcinoma and Adenocarcinoma of the Esophagus–Di?erences in Etiology, Epidemiology and Prevention

In Germany, esophageal carcinoma is one of the ten most frequent causes of death. Normally the disease is found in men over the age of 50. Although squamous cell carcinoma (SCC) of the esophagus has been more commonly diagnosed over the past 30 years, there is increasing incidence of esophageal adenocarcinoma (AC) in Western industrialized countries. For SCC the known etiological risk factors are nicotine and alcohol abuse. For AC, they are moderate nicotine and alcohol consumption as well as gastro-esophageal re?ux and obesity.

A case of rapidly progressing leiomyosarcoma combined with squamous cell carcinoma in the esophagus

Esophageal leiomyosarcoma is a rare tumor that accounts for less than 1%of all malignant esophageal tumors.Esophageal leiomyosarcoma combined with squamous cell carcinoma is even rarer than solitary leiomyosarcoma.We experienced a case of leiomyosarcoma combined with squamous cell carcinoma that progressed very rapidly.

Determination of esophageal squamous cell carcinoma and gastric adenocarcinoma on raw tissue using Raman spectroscopy

BACKGROUND Cancer detection is a global research focus,and novel,rapid,and label-free techniques are being developed for routine clinical practice.This has led to the development of new tools and techniques from the bench side to routine clinical practice.In this study,we present a method that uses Raman spectroscopy(RS)to detect cancer in unstained formalin-fixed,resected specimens of the esophagus and stomach.Our method can record a clear Raman-scattered light spectrum in these specimens,confirming that the Raman-scattered light spectrum changes because of the histological differences in the mucosal tissue.AIM To evaluate the use of Raman-scattered light spectrum for detecting endoscopically resected specimens of esophageal squamous cell carcinoma(SCC)and gastric adenocarcinoma(AC).METHODS We created a Raman device that is suitable for observing living tissues,and attempted to acquire Raman-scattered light spectra in endoscopically resected specimens of six esophageal tissues and 12 gastric tissues.We evaluated formalin-fixed tissues using this technique and captured shifts at multiple locations based on feasibility,ranging from six to 19 locations 200 microns apart in the vertical and horizontal directions.Furthermore,a correlation between the obtained Raman scattered light spectra and histopathological diagnosis was performed.RESULTS We successfully obtained Raman scattered light spectra from all six esophageal and 12 gastric specimens.After data capture,the tissue specimens were sent for histopathological analysis for further processing because RS is a label-free methodology that does not cause tissue destruction or alterations.Based on data analysis of molecular-level substrates,we established cut-off values for the diagnosis of esophageal SCC and gastric AC.By analyzing specific Raman shifts,we developed an algorithm to identify the range of esophageal SCC and gastric AC with an accuracy close to that of histopathological diagnoses.CONCLUSION Our technique provides qualitative information for real-time morphological diagnosis.However,further in vivo evaluations require an excitation light source with low human toxicity and large amounts of data for validation.

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.

Atrophic gastritis: Risk factor for esophageal squamous cell carcinoma in a Latin-American population

AIM: To study the association between atrophic gastritis (AG) and esophageal squamous cell carcinoma (ESCC) in a Latin-America population. METHODS: A case-control study was performed at two reference Brazilian hospitals including patients diagnosed with advanced ESCC and dyspeptic patients who had been subjected to upper gastrointestinal endoscopy, with biopsies of the gastric antrum and body.All cases with ESCC were reviewed by a single pathologist, who applied standard criteria for the diagnosis of mucosal atrophy, intestinal metaplasia, and dysplasia, all classified as AG. The data on the patients' age, sex, smoking status, and alcohol consumption were collected from clinical records, and any missing information was completed by telephone interview. The association between AG and ESCC was assessed by means of univariate and multiple conditional logistic regressions. RESULTS: Most patients were male, and the median age was 59 years (range: 37-79 years) in both the ESCC and control groups. Univariate analysis showed that an intake of ethanol greater than 32 g/d was an independent risk factor that increased the odds of ESCC 7.57 times (P = 0.014); upon multiple analysis, alcohol intake of ethanol greater than 32 g/d exhibited a risk of 4.54 (P = 0.081), as adjusted for AG and smoking. Smoking was shown to be an independent risk factor that increased the odds of ESCC 14.55 times (P = 0.011) for individuals who smoked 0 to 51 packs/year and 21.40 times (P = 0.006) for those who smoked more than 51 packs/year. Upon multiple analyses, those who smoked up to 51 packs/year exhibited a risk of 7.85 (P = 0.058), and those who smoked more than 51 packs/ year had a risk 11.57 times higher (P = 0.04), as adjusted for AG and alcohol consumption. AG proved to be a risk factor that increased the odds of ESCC 5.33 times (95%CI: 1.55-18.30, P = 0.008) according to the results of univariate conditional logistic regression. CONCLUSION: There was an association by univariate conditional logistic regression between AG and ECSS in this sample of Latin-American population.

Clinicopathological and prognostic role of MMP-9 in esophageal squamous cell carcinoma: a meta-analysis

Objective： Many studies reported that matrix metalloproteinase-9 （MMP-9） participated in the development of esophageal squamous cell carcinoma （ESCC） and resulted in poor prognosis, however, they all included few patients and had inconsistent results. So we conducted a meta-analysis to explore the correlation between overexpression of MMP-9 and the clinicopathological characteristics and overall survival （OS） of ESCC. Methods： PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, Google Scholar and other databases were searched for relevant studies. The Newcastle-Ottawa quality assessment scale was used to assess the methodological quality of included study and RevMan 5.2 software was used to conduct meta-analysis. Results： A total of 35 studies were included, and the results of meta-analysis showed that overexpression of MMP-9 was associated with grade of differentiation [well/moderate vs. poor： odds ratio （OR）： 0.39, 95% confidence interval （CI）： 0.29-0.52; P〈0.00001], lymph node metastasis （negative vs. positive： OR： 0.24, 95% CI： 0.16-0.34; P〈0.00001）, TNM stage （T1/T2 vs. T3/T4： OR： 0.28, 95% CI： 0.14-0.54; P=0.0002）, the depth of invasion （T1/T2 vs. T3/T4： OR： 0.29, 95% CI： 0.17-0.49; P〈0.00001）, and vascular invasion of ESCC （negative vs. positive： OR： 0.35, 95% CI： 0.21-0.58; P〈0.0001）, and also associated with poor overall survival ofESCC （HR： 2.17, 95% CI： 1.32-3.57; P=0.002）. Subgroup analysis showed that more than 10% of carcinoma cell staining was associated with significant increase of mortality risk （HR： 2.44, 95 % CI： 1.16-5.15; P=0.02）, and sensitive analysis suggested that MMP-9 was an independent prognostic factor in ESCC （HR： 1.49, 95% CI： 1.16-1.91; P=0.002）. Conclusions：On the basis of limited evidence, overexpression of MMP-9 may be a potential independent prognosis factor of ESCC patients in Asia, and high-quality studies assessing the prognostic significance of MMP-9 for ESCC patients are still needed.

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

曙光 A kinase， serine/threonine 蛋白质 kinase，是潜在的 oncogene。扩大并且在人的肿瘤的几种类型在曙光 A 的表示上被发现了，包括的食道的有鳞的房间癌(ESCC ) 。在表示曙光 A 上的房间对导致 cisplatin 的 apoptosis 更抵抗，这被表明了。然而，调停的分子的机制这些效果仍然保持大部分未知。在这份报告，我们证明在通过在人的 ESCC KYSE150 的 pEGFP-Aurora-A 的稳定的 transfection 的曙光 A 的表示上，房间显著地支持了房间增长并且禁止了 cisplatin- 或紫外导致照耀的 apoptosis。caspase-3 并且 poly 的劈开(自动数据处理核糖) 在在表示房间上的曙光 A 的聚合酶(PARP ) 实质地在 cisplatin 或紫外处理以后被减少。而且，我们发现有 siRNA 的内长的曙光 A kinase 的那 silencing 实质地提高了敏感到导致 cisplatin 或在人的 ESCC EC9706 房间的紫外导致 apoptosis。在平行，在曙光 A 的表示上 potently 起来调整了 Bcl-2 的表示。而且，由废除的 siRNA 的 Bcl-2 击倒 Aurora-A 禁止 apoptosis 上的效果。总起来说，这些数据提供证据在支持房间增长并且禁止 apoptosis 的表示上的那曙光 A，建议是的新奇机制仔细与恶意的显型和 ESCC 房间的反癌症药抵抗有关。

Serum Folate, MTHFR C677T Polymorphism and Esophageal Squamous Cell Carcinoma Risk

This study examined associations between MTHFR C677T polymorphism and serum folate concentrations with the risk of esophageal precancerous lesions （EPL） and esophageal squamous cell carcinoma （ESCC）. The highest quartile of serum folate concentration significantly decreased the risk of ESCC compared with the lowest quartile （0R=0.11; 95% CI, 0.04-0.33; P〈0.05）. MTHFR 677 C〉T polymorphism was associated with the risk of ESCC by using chi-square tests （P〈0.05）. For the CT genotype, the risk of ESCC significantly increased in study participants with low serum folate concentrations （〈26.92μg/L） compared with participants with high serum folate concentrations （〉26.92 μg/L） by using multinomial logistic regression models. The MTHFR genotype may further modify associations between serum folate concentrations and the risk of ESCC, but it was not significantly associated with the risk of EPL.

S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells

AIM:To investigate a potential role of S100A4 in esophagus squamous cell carcinoma metastasis (ESCCs).METHODS:Expression of S100A4 and E-cadherin were analyzed in frozen sections from ESCCs (metastasis,n=28;non-metastasis,n=20) by reverse transcription-polymerase chain reaction,quantitative polymerase chain reaction and immunohistochemistry.To explore the influence of S100A4 on esophageal cancer invasion and metastasis,S100A4 was overexpressed or silenced by S100A4 siRNA in TE-13 or Eca-109 cells in vitro and in vivo.RESULTS:We found the mRNA and protein levels of S100A4 expression in ESCCs was significantly upregulated,and more importantly,that expression of S100A4 and E cadherin are strongly negatively correlated in patients who had metastasis.It was indicated that overexpression of S100A4 in TE-13 and Eca-109 cells downregulates the expression of E-cadherin,leading to increased cell migration in vitro,whereas knockdown of S100A4 inhibited cell migration and upregulation of E-cadherin expression.Moreover,the loss of cell metastatic potential was rescued by overexpression of E-cadherin completely.In addition,nude mice inoculated with S100A4 siRNA-transfected cells exhibited a significantly decreased invasion ability in vivo.CONCLUSION:S100A4 may be involved in ESCC progression by regulate E-cadherin expression,vectorbased RNA interference targeting S100A4 is a potential therapeutic method for human ESCC.

Preoperative sorting of circulating T lymphocytes in patients with esophageal squamous cell carcinoma: Its prognostic significance

AIM: To elucidate the immunologic parameters for the outcome of patients with malignant tumors, especially esophageal squamous cell carcinoma (ESCC) associated with high malignant potential. METHODS: Clinicopathologic features were compared between patients with lower and higher CD4 and CD8 values as well as CD4/CD8 ratio in peripheral blood. RESULTS: The survival rate of patients with higher CD4 value was significantly better than that in patients with lower CD4 value (P = 0.039). The survival rate of patients with higher CD8 value was significantly worse than that of patients with lower CD8 value (P = 0.026). Similarly, the survival rate of patients with higher CD4/ CD8 ratio was significantly better than that of patients with lower CD4/CD8 ratio (P = 0.042). Additionally, multivariate analysis demonstrated that lower CD8 and lower CD4/CD8 ratio were factors independently associated with worse prognosis of patients. CONCLUSION: All the immunologic parameters can predict the outcome of patients with ESCC.

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.

Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer

AIM: To assess the proteome of normal versus tumor tissue in squamous cell carcinoma of the esophagus (SCCE) in Iranian patients and compare our results with former reports by using proteomics. METHODS: Protein was extracted from normal and tumor tissues. Two dimensional electrophoresis was carried out and spots with differential expression were identified with mass spectrometry. RNA extraction and RT-PCR along with immunodetection were performed. RESULTS: Fourteen proteins were found whose expression levels differed in tumor compared to normal tissues. Mass spectrometric analysis resulted in the identification of β-tropomyosin (TMβ), myosin light chain 2 (and its isoform), myosin regulatory light chain 2, peroxyredoxin 2, annexinⅠand an unknown polypeptide as the down regulated polypeptides in tumor tissue. Heat shock protein 70 (HSP70), TPM4-ALK fusion oncoprotein 2, myosin light polypeptide 6, keratinⅠ, GH16431p and calreticulin were the up-regulated polypeptides found in tumor tissue. Several of these proteins, such as TMβ,HSP70, annexinⅠ, calreticulin, TPM4-ALK and isoforms of myosins, have been well recognized in tumorigenesis of esophageal or other types of cancers. CONCLUSION: Our study not only supports the involve- ment of some of the formerly reported proteins in SCCE but also introduces additional proteins found to be lost in SCCE, including TMβ.

Plasma-metabolite-based machine learning is a promising diagnostic approach for esophageal squamous cell carcinoma investigation

The aim of this study was to develop a diagnostic strategy for esophageal squamous cell carcinoma(ESCC)that combines plasma metabolomics with machine learning algorithms.Plasma-based untargeted metabolomics analysis was performed with samples derived from 88 ESCC patients and 52 healthy controls.The dataset was split into a training set and a test set.After identification of differential metabolites in training set,single-metabolite-based receiver operating characteristic(ROC)curves and multiple-metabolite-based machine learning models were used to distinguish between ESCC patients and healthy controls.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic significance of the plasma metabolites.Finally,twelve differential plasma metabolites(six up-regulated and six down-regulated)were annotated.The predictive performance of the six most prevalent diagnostic metabolites through the diagnostic models in the test set were as follows:arachidonic acid(accuracy:0.887),sebacic acid(accuracy:0.867),indoxyl sulfate(accuracy:0.850),phosphatidylcholine(PC)(14:0/0:0)(accuracy:0.825),deoxycholic acid(accuracy:0.773),and trimethylamine N-oxide(accuracy:0.653).The prediction accuracies of the machine learning models in the test set were partial least-square(accuracy:0.947),random forest(accuracy:0.947),gradient boosting machine(accuracy:0.960),and support vector machine(accuracy:0.980).Additionally,survival analysis demonstrated that acetoacetic acid was an unfavorable prognostic factor(hazard ratio(HR):1.752),while PC(14:0/0:0)(HR:0.577)was a favorable prognostic factor for ESCC.This study devised an innovative strategy for ESCC diagnosis by combining plasma metabolomics with machine learning algorithms and revealed its potential to become a novel screening test for ESCC.

Nicotine enhances migration and invasion of human esophageal squamous carcinoma cells which is inhibited by nimesulide

AIM:To study the effect of nicotine on the migration and invasion of human esophageal squamous carcinoma cells and to investigate whether nimesulide can inhibit the effect of nicotine.METHODS:The esophageal squamous carcinoma cell line(TE-13) was treated with different concentrations of nicotine(100 μg/mL and 200 μg/mL) or 200 μg/mL nicotine plus 100 μmol/L nimesulide.Cell migration and invasion were measured using migration and invasion chamber systems.COX-2 expression was determined by Western blotting.Matrix metalloproteinase-2(MMP-2) was analyzed by zymography and ELISA.RESULTS:Nicotine(100 μg/mL, 200 μg/mL) enhanced TE-13 cells migration and invasion, and increased the protein expression of COX-2 and the activity of MMP-2.Nicotine(200 μg/mL) stimulated TE-13 cells migration and invasion which were partly blocked by nimesulide.This was associated with decreased protein expression of COX-2 and decreased activity and protein expression of MMP-2.CONCLUSION:Nicotine enhances the migration and invasion of the esophageal squamous carcinoma cell line, and nimesulide partly blocks the effect ofnicotine-enhanced esophageal squamous carcinoma cell migration and invasion.

The relationship between treatment-induced hypertension and efficacy of anlotinib in recurrent or metastatic esophageal squamous cell carcinoma

Objective:In this post-hoc analysis,we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma(ESCC)patients.Methods:A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included.The tumor response was assessed by computed tomography at week 3,week 6,and then every 6 weeks until progressive disease was observed.The primary endpoint of the study was progression free survival(PFS).The secondary endpoints included overall survival(OS)and objective response rate(ORR).Results:In all patients,the median PFS was 3.02 months[95%confidence interval(CI):2.63–3.65 months]and the OS was 6.11 months(95%CI:4.40–7.79 months).The ORR was 7.34%(95%CI:3.22%–13.95%).A total of 59(54%)patients were diagnosed with treatment-induced hypertension(Group A),and the remaining patients(n=50,46%)were in Group B.Baseline prognostic factors were similar between the 2 groups.Patients in Group A had a longer PFS and OS and higher ORR.When stratifying patients using a previously known history of hypertension,treatment-induced hypertension was a predictor only for patients without previous hypertension,who had longer PFS[hazard ratio(HR):0.40,95%CI:0.24–0.68]and OS(HR:0.37,95%CI:0.21–0.67).Conclusions:We showed,for the first time,a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib,without a previously known history of hypertension.Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients,which may also reflect the intended target inhibition.

Expression and clinical significance of HIF-1α,VEGF and Survivin in esophageal squamous cell carcinoma

Objective:To evaluate the expression and correlation of hypoxia inducible factor 1α(HIF-1α)and vascular endothelial growth factor(VEGF)and Survivin proteins in biopsy specimens of esophageal squamous cell carcinoma(ESCC), and then determine whether the levels of expression of these proteins could predict the clinical effectiveness of radiotherapy in individual cancers.Methods:The expressions of HIF-1α,VEGF and Survivin were shown by S-P immunohistochemical stainingmethodinbiopsyspecimensofESCC,whichwereobtainedendoscopicallyfrom50patientsbeforeradiotherapy,and 10 cases of normal esophageal tissue.Results:The positive expression rates of HIF-1α,VEGF and Survivin were 68%,74% and72%inESCCrespectively.However,thethreetumormarkershadnegativeexpressionsinnormalesophagealtissue.The positive rate of HIF-1αwas positively correlated with VEGF and Survivin proteins.The positive rates of HIF-1αand Survivin were closely related to the clinical stage,radiotherapy effectiveness and survival,otherwise,the expression of HIF-1αwas closely related to distant metastasis;both of them were no correlation with the differentiation degree of tumor.The effective rates of radiotherapy and mean survival periods of those cases with positive and negative expressions of HIF-1αwere 8.8%, 10 months and 81.25%,25 months,respectively.The one,two,and three years survival rates of patients with positive and negative expressions of HIF-1αwere 38.2%,5.9%,2.9%,and 81.3%,54.2%,15.8%,respectively(P=0.001).Patients with HIF-1αpositive expression obviously survived less than those with negative expression and the difference was significant. The expression of VEGF was only related to the distant metastasis.Conclusion:Over expressions of HIF-1α,VEGF and Survivin were found in ESCC.The positive rate of HIF-1αwas positively correlated with VEGF and Survivin proteins.The expression of HIF-1αmay serve as an important parameter in evaluating response for radiotherapy and prognosis of ESCC. It may play an important role by up-regulating the transcription of VEGF and Survivin genes.

An extremely rare case of pancreatic metastasis of esophageal squamous cell carcinoma

We report a rare case of a 68-year-old male with metachronous pancreatic metastasis that was resected2 years after salvage esophagectomy for local recurrence of esophageal squamous cell carcinoma(ESCC).Two years and 8 mo ago,he had undergone definitive chemoradiotherapy for the lower thoracic ESCC and achieved a complete response.Chemoradiotherapy used the protocol of the Japan Clinical Oncology Group trial 9906.Approximately 8 mo later,he developed a local recurrence of the ESCC and underwent thoracoscopic salvage esophagectomy followed by reconstruction with a conduit colon graft via a subcutaneous route.Recently,a tumor of the pancreatic body was found on routine follow-up computed tomography(CT).The tumor diameter was 15 mm on CT,and the maximum standardized uptake value of the lesion was 5.49at 18F-2-fluoro-2-deoxy-D-glucose positron-emission tomography,strongly suggesting pancreatic cancer.In addition,all tumor markers were within the reference intervals.Therefore,distal pancreatectomy was performed with the resultant histological diagnosis being confirmed as pancreatic metastasis of the ESCC.He was treated with adjuvant chemotherapy,and there has been no evidence of recurrence 9 mo after the surgery.Resection of pancreatic metastasis offers a good prognosis and should be considered for solitary ESCC metastasis.