Early Esophageal Cancer Patients Research Articles

Combining non-invasive liquid biopsy and a methylation analysis to assess surgical risk for early esophageal cancer.

While the widespread use of endoscopic submucosal dissection (ESD) has significantly reduced the incidence of early esophageal cancer (ESCA), the limited ability of ESD to strip deep infiltrating esophageal lesions results in a considerable risk of intraoperative perforation. Circulating-free DNA (cfDNA) is widely used in modern tumor screening due to its non-invasive detection capabilities. A methylation analysis offers vital insights into the condition and advancement of malignancies due to its unique positioning, such as a marker of cancer. This study investigated the potential of combining a non-invasive liquid biopsy technique, along with a methylation analysis, to assess the surgical perforation risk of ESCA patients. In this study, we conducted an analysis of gene expression differences between stage I esophageal squamous carcinoma samples and healthy tissue samples using data from The Cancer Genome Atlas (TCGA) database. We also identified the genes associated with progression-free survival (PFS) in esophageal squamous carcinoma. Integrating the framework of the methylation analysis, we explored the methylated sites of these distinct genes. To refine this process, we used the Shiny Methylation Analysis Resource Tool (SMART) to conduct a comprehensive analysis of these sites. We then confirmed the stability of the methylation sites in different lesion conditions using methylation-specific quantitative polymerase chain reaction (MS-qPCR) with paraffin tissue samples collected after ESD. We analyzed RNA-sequencing data from 42 early stage ESCA patients and 17 controls, identifying 1,263 up-regulated and 460 down-regulated genes. Functional analyses revealed involvement in key pathways such as cell cycle regulation and immune responses. Furthermore, we identified 38 differentially expressed genes associated with PFS. Using SMART analysis, we found 217 hyper-methylated regions in 38 genes, suggesting potential early markers for ESCA. Validation experiments confirmed the reliability of 29 hyper-methylated regions in FFPE tissue samples and 6 regions in cfDNA. A LunaCAM model showed high accuracy [area under the curve (AUC) =0.89] in discriminating early ESCA. Integrated assessment of six highly methylated regions significantly improved predictive performance, with 90.56% sensitivity, highlighting the importance of combinatorial biomarker evaluation for early cancer detection. This study established a novel approach that integrates non-invasive testing with a methylation analysis to assess the surgical risk of early ESCA patients. The significance of changes in methylation sites in relation to lesion status should not be underestimated, as they have the potential to offer vital insights for proactive risk assessments before surgery.

Endoscopic submucosal dissection for early esophageal squamous cell carcinoma after ligation and sclerotherapy of esophageal and gastric varices

Esophageal cancer ranked ten of the most common cancers in China. With the advancement of high-quality endoscopy and chromoendoscopic technique, early esophageal cancer can be diagnosed more easily, even combined with esophageal-gastric fundal varices. Endoscopic resection of early esophageal cancer is a minimally invasive treatment method for early esophageal cancer, and endoscopic submucosal dissection (ESD) is one of the standard treatments for early esophageal cancer in view of the risk of bleeding, the patient in this study successfully received ESD treatment after using endoscopic variceal ligation and endoscopic injection of tissue glue and sclerosing agent before ESD surgery. ESD treatment is safe and feasible for early esophageal cancer patients with cirrhosis of esophageal-gastric fundal varices.

The association between histological subtypes and lymph node metastasis and prognosis in early esophageal cancer: a population-based study.

There is still a lack of high-level clinical evidence and uniform conclusions on whether there are differences in lymph node metastasis (LNM) and prognosis between early esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). Patients with surgically resected, histologically diagnosed, pT1 EAC or ESCC in the Surveillance, Epidemiology and End Results registries database from 2004 to 2015 were included. Multivariable logistic regression, Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the histology and LNM or prognosis. A total of 570 early esophageal cancer patients were included. The LNM rates were 13.8% and 15.1% for EAC and ESCC ( P = 0.757), respectively. Multivariate logistic regression analysis showed no significant association between histological type and LNM (odds ratio [OR], 1.209; 95% CI, 0.538-2.715; P = 0.646). Moreover, the prognosis of early EAC and ESCC was shown to be comparable in both multivariate Cox regression (hazard ratio [HR], 1.483; 95% CI, 0.699-3.150; P = 0.305) and the multivariate competing risk model (subdistribution HR, 1.451; 95% CI, 0.628-3.354; P = 0.383). After propensity score matching, there were no significant differences between early EAC and ESCC in terms of LNM (10.6% vs.18.2%, P = 0.215), 5-year CSS (89.8% [95% CI, 81.0%-98.6%] vs. 79.1% [95% CI, 67.9%-90.3%], P = 0.102) and 5-year cumulative incidence of CSS (10.2% [95% CI, 1.4%-19.0%] vs. 79.1% [95% CI, 9.7%-32.1%], P = 0.124). The risk of LNM and prognosis of early ESCC and EAC are comparable, so the treatment choice for early esophageal cancer does not depend on the histologic type.

Prognostic analysis and nomogram establishment in patients with early esophageal cancer receiving endoscopic therapy: a population-based study.

The growing numbers of early esophageal cancer (EEC) have increased the demand for endoscopic therapy. To clarify the influential factors for the prognosis of patients with EEC receiving endoscopic surgery, and to construct a nomogram to evaluate the prognostic value of endoscopic therapy. Prognostic analysis study. Clinical data of EEC patients who received endoscopic therapy between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results database and used to construct the nomogram. The prognosis was analyzed by R language; the nomogram was constructed by Cox survival analysis; and the accuracy of the nomogram was verified by C index and the receiver operating characteristic (ROC) and calibration curves. X-Tile software was used to stratify the risk of patients. Our study constructed the nomogram of the prognosis of patients with EEC treated by endoscopic surgery, including 1118 patients and 5 independent prognostic factors of esophageal cancer-specific survival. The C index and the area under the ROC curve (AUC) of the training and verification cohorts were all >0.75. The calibration curve also reflected the good consistency of the model in predicting survival. Significant difference in the risk of patients from different stratifications with the same T staging existed, and the model had a better C index than that of the T staging. Our study reports potential influential factors affecting the prognosis of EEC patients who received endoscopic therapy and establishes a reliable nomogram to predict the risk and prognosis, which has certain advantages compared with traditional TNM staging system.

Clinical models to predict lymph nodes metastasis and distant metastasis in newly diagnosed early esophageal cancer patients: A population-based study.

Patients with early esophageal cancer (EC) receive individualized therapy based on their lymph node metastasis (LNM) and distant metastasis (DM) status; however, deficiencies in current clinical staging techniques and the issue of cost-effectiveness mean LNM and DM often go undetected preoperatively. We aimed to develop three clinical models to predict the likelihood of LNM, DM, and prognosis in patients with early EC. The Surveillance, Epidemiology, and End Results database was queried for T1 EC patients from 2004 to 2015. Multivariable logistic regression and Cox proportional hazards models were used to recognize the risk factors of LNM and DM, predict overall survival (OS), and develop relevant nomograms. Receiver operating characteristic (ROC)/concordance index and calibration curves were used to evaluate the discrimination and accuracy of the three nomograms. Decision curve analyses (DCAs), clinical impact curves, and subgroups based on model scores were used to determine clinical practicability. The area under the curve of the LNM and DM nomograms were 0.668 and 0.807, respectively. The corresponding C-index of OS nomogram was 0.752. Calibration curves and DCA showed an effective predictive accuracy and clinical applicability. In patients with T1N0M0 EC, surgery alone (p < 0.01) proved a survival advantage. Chemotherapy and radiotherapy indicated a better prognosis in the subgroup analysis for T1 EC patients with LNM or DM. We created three nomograms to predict the likelihood of LNM, DM, and OS probability in patients with early EC using a generalizable dataset. These useful visual tools could help clinical physicians deliver appropriate perioperative care.

Novel Transgastric Endoluminal Segmental Esophagectomy and Primary Anastomosis Technique: A Hybrid Transgastric Thoracoscopic Esophagectomy for the Treatment of High Grade Dysplasia and Early Esophageal Cancer in a Porcine Ex vivo Model.

Multiple modalities are currently employed in the treatment of high grade dysplasia and early esophageal carcinoma. While they are the subject of ongoing investigation, surgery remains the definitive modality for oncological resection. Esophagectomy, however, is traditionally a challenging surgical procedure and carries a significant incidence of morbidity and mortality. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are considerably less invasive alternatives to esophagectomy in the diagnosis and treatment of high grade dysplasia, early esophageal squamous cell carcinoma and adenocarcinoma. However, many early esophageal cancer patients, with favorable histology, who could benefit from endoscopic resection, are referred for formal esophagectomy due to lesion characteristics such as unfavorable lesion morphology or recurrence after previous endoscopic resection. In this study we present a novel, hybrid thoracoscopic transgastric endoluminal segmental esophagectomy with primary anastomosis for the potential treatment of high grade dysplasia and early esophageal cancer in a porcine ex vivo model as a proposed bridge between endoscopic resection and the relatively high mortality and morbidity formal esophagectomy procedure. The novel technique consists of thoracoscopic esophageal mobilization in addition to transgastric endoluminal segmental esophagectomy and anastomosis utilizing a standard circular stapler. The technique was found feasible in all experimental subjects. The minimally invasive nature of this novel procedure as well as the utility of basic surgical equipment and surgical skill is an important attribute of this method and can potentially make it a treatment option for many patients who would otherwise be referred for a formal esophagectomy.

Predictive Value of Routine Blood Test in patients with Early Esophageal Cancer: A Matched Case-Control Study.

Aims: The present study was to evaluate the diagnostic value of routine blood test as potential inflammatory markers in early esophageal cancer (EEC) patients.Methods: A matched case-control study was conducted by recruiting 314 patients who were pathologically diagnosed with EEC and then underwent Endoscopic Submucosal Dissection (ESD) from July 2015 to July 2019 in First Affiliated Hospital of Nanjing Medical University. Each EEC patient was matched against one healthy control on the criteria of gender, and age (±2 years). Additionally, a total of 40 subjects (20 cases and 20 controls) were also included in the validation set. Statistical analysis of selected hematological parameters was performed between the two groups. The correlation between preoperative blood indexes and clinicopathological characteristics after ESD in EEC patients were further assessed.Results: Mono-factor analysis showed that the index of monocyte (p<0.001), MCV (p=0.018), MCH (p=0.01), MPV (p=0.022), PT (p=0.003), PT-INR (p=0.003), PDW (p<0.001) and MLR (p<0.001) were statistically significant in EEC patients when compared with those in healthy controls. Multivariate logistic regression analysis further identified that PDW and MLR was independently associated with the risk of early esophageal cancer (both p<0.001). The higher level of NLR (P=0.007) and MLR (P=0.015) were statistically significant with submucosal invasion in EEC patients and the level of MLR were significantly associated with larger tumor size (P=0.030). The results of the validation group were in consistence with the primary group.Conclusions: Hematological parameters of MLR and PDW can be used as an adjuvant tool for the diagnosis of EEC. Moreover, the value of MLR can reflect the invasion depth index.

Comparison of endoscopic injection of botulinum toxin and steroids immediately after endoscopic submucosal dissection to prevent esophageal stricture: a prospective cohort study.

Background: Widespread endoscopic submucosal dissection (ESD) in early esophageal cancer patients is closely associated with esophageal stricture, which dramatically reduces patients' quality of life and increases huge medical burdens. Endoscopic injection of steroid was proved as a protective method for post-ESD strictures. Other materials such as botulinum toxin type A (BTX-A) may be potential candidates. We conducted this prospective cohort study to compare the efficacy and feasibility of endoscopic injection of BTX-A and triamcinolone acetonide (TA) for the prevention of esophageal stricture.Methods: Seventy-eight patients with esophageal mucosal defects of more than two thirds of the circumference were successively enrolled and divided into 3 groups: BTX-A group (group A, n=26), TA group (group B, n=16) and control group (group C, n=36). Patients in group A were immediately injected with BTX-A after ESD, in group B were immediately injected with TA and in group C received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 6 and 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in all groups received bougie dilation. All patients were followed up for one year.Results: The proportion of patients developing stricture in BTX-A group was 30.00% (intention to treat analysis, 9/30) and 26.92% (per protocol analysis, 7/26), in TA group was 40.90% (intention to treat analysis, 9/22) and 43.75% (per protocol analysis, 7/16), and in control group was 84.21% (intention to treat analysis, 32/38) and 83.33% (per protocol analysis, 30/36) (p<0.001). When further comparing between each of the two groups, the incidence of esophageal stricture was lower in BTX-A group than that in control group (p<0.001), and lower in TA group than that in control group (p=0.004). Furthermore, in entire circumference mucosal defect subgroup, the esophageal stricture was significantly lower in BTX-A group than that in TA group (33.3% vs 100%, p=0.0454).Conclusions: Endoscopic injection of BTX-A and TA were effective in preventing post-ESD esophageal strictures and BTX-A injection was particularly effective in entire circumference mucosal defect patients. Multi-centered, randomized prospective study with larger sample size should be conducted. (Clinical trial registration number: ChiCTR2100042970, registered 1 February 2021, retrospectively registered, http://www.chictr.org.cn/listbycreater.aspx)

Potential miRNA biomarkers for the diagnosis and prognosis of esophageal cancer detected by a novel absolute quantitative RT-qPCR method

miRNAs are expected to become potential biomarkers in the diagnosis and prognosis of Esophageal cancer (EC). Through a series of screening, miR-34a-5p, miR-148a-3p and miR-181a-5p were selected as EC-associated miRNAs. Based on AllGlo probe, a novel absolute quantitative RT-qPCR method with high sensitivity, specificity and accuracy was established for detecting miRNAs. Then the clinical significance of these 3 miRNAs was explored with 213 patients (166 cases with EC and 47 cases with benign diseases) and 170 normal controls. Compared with normal controls, the level of miR-34a-5p increased while miR-148a-3p and miR-181a-5p decreased in EC and benign patients (P < 0.001), and the level of miR-181a-5p in early EC patients was significantly lower (P < 0.001). According to logistic regression analysis, combined detection of miR-34a-5p, miR-148a-3p and Cyfra21-1 provided the highest diagnosis efficiency of 85.07% with sensitivity and specificity reaching 85.45% and 84.71%. Compared with preoperative samples, the level of miR-34a-5p decreased while miR-148a-3p and miR-181a-5p increased in postoperative samples (P < 0.001). Collectively, this first developed, novel absolute quantitative RT-qPCR method exhibits high application value in detecting miRNAs, miR-34a-5p, miR-148a-3p and miR-181a-5p may serve as potential biomarkers in the diagnosis and prognosis of EC, and miR-181a-5p probably could serve as a new biomarker for early EC.

Effects of anxiety, depression, and fatigue on quality of life in early esophageal cancer patients following endoscopic submucosal dissection.

Emotional problems such as anxiety, depression, and fatigue may affect the quality of life (QoL) of cancer patients. However, there are no related studies investigating the effects of emotional problems on the QoL of early esophageal cancer (EC) patients receiving endoscopic submucosal dissection (ESD). This is a prospective observational study enrolling 75 early EC patients. Demographic and clinical characteristics of enrolled patients were recorded. QoL was assessed according to the European Organization for Research and Treatment of Cancer QoL (EORTC QLQ-C30). The Beck Anxiety Scale and the Beck Depression Scale were used to measure the severity of anxiety symptoms and depression intensity, respectively. Fatigue was assessed according to the symptom subscale of the EORTC QLQ-C30. Multivariable logistic regression models were constructed to determine the causes of emotional problems and linear regression models were employed to identify the independent risk factors for reduced QoL. Of the enrolled early EC patients, 21, 15, and seven had symptoms of mild, moderate and severe anxiety, respectively. Also, 15, 19, and two patients had symptoms of mild, moderate, and severe depression, respectively. In total, 27 patients frequently felt fatigue. The multivariable logistic regression model revealed that the financial capacity to pay for treatment had an important effect on the prevalence of anxiety and depression symptoms in enrolled patients (both P values <0.001). Age, gender, education status, and tumor size also played a role in emotional problems. Meanwhile, fatigue was found to be related only to age and gender. The mean score for QoL was 76.9±15.2. After adjusting for confounding factors using the multivariable linear regression model, moderate or severe symptoms of anxiety, depression, and fatigue, older age, and insufficient capacity to pay were identified as independent risk factors for reduced QoL. Emotional distress is a significant problem for early EC patients receiving ESD treatment as it may affect their QoL.

Chemoradiotherapy vs radiotherapy for nonoperative early stage esophageal cancer: A seer data analysis.

BackgroundThe benefit of endoscopic treatment (ET) and esophagectomy for early esophageal cancer (EC) has been sufficiently recognized. Radiotherapy (RT) is the main treatment modality for patients who do not undergo surgery. The effectiveness of adding chemotherapy (CT) to RT remains unclear. This study aimed to evaluate the impact of chemoradiotherapy (CRT) and RT alone on overall survival (OS) and cancer‐specific survival (CSS) in early EC patients not undergoing surgery.MethodsData collected between 2004 and 2015 were obtained from the national Surveillance, Epidemiology, and End Results (SEER) database. All the samples were randomly grouped into the training cohort or the verification cohort. The training cohort was split into subgroups by stage, age, and histology. Stage was based on the American Joint Committee on Cancer (AJCC) 6th edition published in 2004. The Kaplan‐Meier method and Cox proportional hazards modeling were used to compare OS and CSS. The performance of the nomogram was measured by a concordance index (C‐index) and the calibration curve.ResultsData for a total of 5332 patients were obtained from the SEER database. A total of 3736 patients (stage I: n = 1277; stage IIA: n = 1484; stage IIB: n = 975) were used for the training cohort. Multivariate Cox regression analysis showed that age, sex, histology, grade, therapy, reasons for no surgery, and year of diagnosis were independent predictors of OS. The survival curve of patients treated with CRT showed a significant survival benefit compared to that in patients treated by RT alone in stage I, stage IIA, and stage IIB. CRT was also found to be related to better survival than RT in patients at a younger age (<65) and an older age (≥65) with squamous cell carcinoma or adenocarcinoma.ConclusionsCompared with RT, CRT results in better OS and CSS in early EC patients who do not undergo surgery.

A prospective study of optical coherence tomography for predicting invasion depth of early esophageal cancer

Objective To evaluate optical coherence tomography(OCT)for predicting invasion depth of early esophageal cancer(EEC) and to compare OCT and magnifying endoscopy-narrow band imaging (ME-NBI)in clinical performance. Methods Twenty-eight patients who were diagnosed with EEC and accepted OCT and ME-NBI before endoscopic submucosal dissection(ESD)were enrolled in this prospective study. On the basis of OCT and ME-NBI images, real-time prediction of EEC invasion depth was conducted. Postoperative pathological results were taken as golden standard to compare the accuracy of OCT and ME-NBI in evaluation of EEC invasion depth. The procedure time and incidence of complications during evaluation process were also analyzed. Results The overall accuracy of OCT and ME-NBI in predicting invasion depth of 28 EEC patients were 67.9% (19/28) and 75.0% (21/28) respectively, with no significant difference(P>0.05). The accuracy of OCT and ME-NBI in distinguishing lesions located in epithelium/lamina propria mucosa (EP/LPM) lesions were 78.9%(15/19) and 68.4% (13/19), with no significant difference(P>0.05). The procedure time of OCT was significantly shorter than that of ME-NBI (6.0±2.9 min VS 16.3±5.4 min, P<0.001). Conclusion The ability of OCT to predict invasion depth of EEC and distinguish lesions located in the EP/LPM is comparable with that of ME-NBI. Besides, OCT requires shorter procedure time for evaluation. Key words: Tomography, optical coherence; Esophageal neoplasm; Invasion depth; Magnifying endoscopy with narrow band imaging; Accuracy

Predictors of Pathologic Upstaging in Early Esophageal Cancer Patients: Results from the National Cancer Data Base

Predictors of Pathologic Upstaging in Early Esophageal Cancer Patients: Results from the National Cancer Data Base

Influence on Daily Life of Early Esophageal Cancer Patients After Total Extirpation with Reconstruction by Retrosternal Substitution of the Esophagus

Influence on Daily Life of Early Esophageal Cancer Patients After Total Extirpation with Reconstruction by Retrosternal Substitution of the Esophagus

Updates on endoscopic therapy of esophageal carcinoma.

Endoscopic submucosal dissection (ESD) has the advantage over endoscopic mucosa resection (EMR), permitting removal of gastrointestinal neoplasms en bloc, but is associated with a relatively high risk of complications. Early esophageal cancer (EEC) is indicated when the tumors are confined to the two-third layer of the lamina propria. Esophageal stricture following semicircular or complete circular esophageal ESD is relatively frequent even if treated by multiple pre-emptive endoscopic balloon dilatation. Oral prednisolone may offer a novel, safe, and effective option for prevention of post-ESD stricture associated with ESD for extensive esophageal neoplasms. The procedures include marking, submucosal injection, circumferential mucosal incision and exfoliation of the lesion along the submucosal layer. Complete ESD can achieve a large one-piece resection, allowing precise histological assessment to prevent recurrence. Clinical outcomes of esophageal ESD have been promising, and the prognosis of EEC patients treated by ESD is likely to be excellent, though further long-term follow-up studies are warranted. Notification of a risk of perforation is essential for esophageal ESD. Bleeding during ESD can be managed with coagulation forceps, and postoperative bleeding may be reduced with routine use of the stronger acid suppressant, proton pump inhibitors.

Increased IL-17-producing CD4 + T cells in patients with esophageal cancer

Increased interleukin-17 (IL-17)-producing Th (Th17) cells have been described in a variety of human carcinoma cases, however, the mechanism of Th17 cells’ accumulation in a tumor microenvironment remains elusive. This study was designed to investigate whether Th17 cells were involved in the development of esophageal cancer. We found that the proportion of Th17 cells increased within the peripheral blood and tumor tissues of esophageal cancer patients. Furthermore, the proportion of circulating Th17 cells was higher in advanced esophageal cancer patients than that in early esophageal cancer patients. In addition, the Th17 cells differentiation-related cytokines (IL-23, IL-1β, and IL-6) and accumulation-related chemokines (CCL22 and CCL20) were present in a tumor microenvironment. Therefore, the findings may partly explain the cause for the increased proportion of Th17 cells and indicate a potential prognostic marker of Th17 cells in esophageal cancer.

Risk of perforation during dilation for esophageal strictures after endoscopic resection in patients with early squamous cell carcinoma

Growing evidence suggests that esophageal stricture frequently develops after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in early esophageal cancer patients, with an incidence proportional to the greater extent of mucosal defects resulting from improved EMR/ESD techniques. There seems to be a potential risk of perforation during bougienage in such patients. 648 stricture dilations for 78 lesions in 76 patients were consecutively included. The outcomes after combined use of Maloney and Savary wire-guided bougienage for esophageal strictures after EMR/ESD were analyzed in a single-institute retrospective case series study. The perforation rate was determined and risk factors for perforation were identified. Patients underwent a median of 5.0 dilation procedures performed over a median 3.0 months for post-EMR/ESD strictures. Initial dilation was done a median 14 days following endoscopic resection. Perforations developed in seven patients (7/648 dilation procedures, 1.1%), all in the lower esophagus, and bleeding occurred in one patient (0.1% dilations). Two independent risk factors for development of perforation during dilation therapy for post-EMR/ESD stricture were identified: multiple dilations (odds ratio [OR] 1.2; P=0.012), and lower site of stricture (OR 12.8; P=0.043). Dysphagia was ameliorated by the dilations, and no patient required surgery. A specific emerging risk of perforation in dilation therapy for post-EMR/ESD strictures was identified. Carefully planned treatment is necessary in patients with severe post-EMR/ESD strictures especially strictures requiring multiple dilations or located in the lower esophagus.

Expression profiles of early esophageal squamous cell carcinoma by cDNA microarray

An effective way to decrease the mortality rate in esophageal cancer (EC) is to provide diagnosis and treatment for early EC patients. Identification of molecular markers would be helpful for early diagnosis. In this study, we obtained the gene expression profile of early esophageal squamous cell carcinoma (ESCC) and further screened molecular markers that might be useful in early diagnosis and treatment. RNA extracted from EC cancer tissues and matched normal esophageal epithelium of four EC patients were analyzed using whole-genome microarrays. Welch's t-test was applied to normalized data to identify genes expressed differently between cancer and normal tissues. Significantly differentially expressed genes were classified according to gene ontology. Gene mapping software was used to identify pathways involving the genes that were significantly changed. Among the 54,613 gene transcripts and variants analyzed, 367 were differentially expressed between early ESCC and normal esophageal epithelium (Welch's t-test, P < 0.01). Specifically, 104 genes were significantly upregulated and 263 were downregulated in early ESCC, compared with normal esophageal epithelium. Functional gene sets expressed differentially between ESCC cancer and normal tissues included those involved in gene transcription, cell proliferation, motility, apoptosis, and metabolism (specifically, pathways of cell apoptosis, the cell cycle, G protein, and TGF-β signal transduction). We conclude that a large number of genes are involved in the occurrence and development of early ESCC and take part in various cell processes and pathways. The present findings contribute theoretical information for further screening of genes related to early ESCC.

Endoscopic Full-Thickness Resection (EFTR) with Sutured Closure of Defect: Wedge Resection for Gastric Tumours

Endoscopic Full-Thickness Resection (EFTR) with Sutured Closure of Defect: Wedge Resection for Gastric Tumours Keiichi Ikeda, Paul Swain, Sandy Mosse, Tim Mills, Hisao Tajiri, Annette Fritscher-Ravens Background: Tumours, which extend into the deep submucosa or proximal muscularis propria or further, might be advantageously staged and treated by full thickness resection if secure methods for performing the procedure and closing the defect were available. Full thickness resection would allow more complete histological examination of the cancer and allow less-invasive removal of more deeply penetrating cancers, which have not spread to the serosal surface. A method for rapid closure of full thickness defects in the stomach wall would be valuable for other flexible endosurgical applications. Aims: 1. To test the feasibility of full thickness gastric wedge resection and defect closure. 2. To develop methods for suturing full thickness defects or perforations in the stomach. Materials and Methods: A new sewing method was developed using a flexible sheathed needle with a metal tag and thread at the tip, which passes through the accessory channel. Prototype cutting and knot-tying devices closed the defect after full-thickness resection. Full-thickness wedge resection was achieved by two methods. 1. Aspiration method using a ligating device without submucosal injection with subsequent snare removal. 2. A circumferential cutting method using an insulated tip knife. They were studied in survival experiments in pigs (n=10). A check endoscopy was performed at 7 days after the procedure and again at 21-28 days with subsequent retrieval of the healed defect for further examination at postmortem. At the time of the last endoscopy the EFTR procedure was repeated. Tests of water-tightness and measurements of the force required to pull out the stitches were performed at post-mortem. Results: It was possible to take full-thickness wedge resections from the gastric wall (100%: 20/20) and close the defect after resection using sewing, cutting and knot-tying devices (100%: 20/20). Water tightness at the suturing site was confirmed in experiment at postmortem (100%: 10/10). A healing ulcer at the suturing site was evident at follow-up endoscopy in experiment with survival pigs. The pullout force with stitches using this new sewing method was significantly higher than with endoscopic clips (20.3NG 0.94 vs. 2.2G 0.42, p ! 0.05). There were no serious complications during these experiments. Conclusion: Full-thickness gastric wedge resection with sutured defect closure was feasible and appeared safe in these survival experiments. New methods of sutured defect closure are presented. 221 Novel Procedure of Endoscopic Submucosal Dissection (ESD) Using a New Device (MUCOSECTOME) Yoshiro Kawahara, Atsushi Imagawa, Shigeatsu Fujiki, Yasushi Shiratori Backgrounds: En-bloc resection is beneficial for accurate histological assessment of resected specimen of Endoscopic mucosal resection (EMR). Variable EMR methods were developed. Conventional EMR technique or technique using Cap device method (EMRC) is technically simple and convenient but with this procedure the size of specimen obtained from one-piece resection is very limited. Endoscopic submucosal dissection (ESD) procedure using IT knife, Hook knife, Flex knife, etc. has already reported and it is actually useful to some expert endoscopists of it, but sometimes difficult for general endoscopists to use it safely. We developed a safe and easy technique of the ESD using a new device (Mucosectome, Prototype, Pentax Japan). Device and Methods: Mucosectome is an electrosurgical device, which is newly developed for ESD. Mucosectome is composed with flexible plastic shaft and cutting wire. Traction applied on the handle manipulates the tip of the Mucosectome to assist in the proper alignment of the cutting wire to the tissue. Plastic shaft moves a muscular layer side; cutting wire moves a mucosal layer side of the submucosa during ESD, and then procedure itself becomes safe. Results: 65 cases of early gastric cancer and 5 cases of early esophageal cancer patients received ESD using Mucosectome. En-bloc resection of the lesion succeeded in 67 cases. Dissection of the submucosa was very easily and quickly carried out. Minor bleeding including oozing occurred in 9.8% and no perforation encountered. Conclusion: Here we present a new method of ESD using Mucosectome, which can realize safer, easier, and less time-consuming ESD compared to previous methods. By using this device, general endoscopists may also be able to performe ESD safely.