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Sample records for esophageal adenocarcinoma ea

  1. Genetic Insights in Barrett's Esophagus and Esophageal Adenocarcinoma.

    PubMed

    Reid, Brian J; Paulson, Thomas G; Li, Xiaohong

    2015-10-01

    Beginning in the 1980s, an alarming rise in the incidence of esophageal adenocarcinoma (EA) led to screening of patients with reflux to detect Barrett's esophagus (BE) and surveillance of BE to detect early EA. This strategy, based on linear progression disease models, resulted in selective detection of BE that does not progress to EA over a lifetime (overdiagnosis) and missed BE that rapidly progresses to EA (underdiagnosis). Here we review the historical thought processes that resulted in this undesired outcome and the transformation in our understanding of genetic and evolutionary principles governing neoplastic progression that has come from application of modern genomic technologies to cancers and their precursors. This new synthesis provides improved strategies for prevention and early detection of EA by addressing the environmental and mutational processes that can determine "windows of opportunity" in time to detect rapidly progressing BE and distinguish it from slowly or nonprogressing BE. PMID:26208895

  2. Recent developments in esophageal adenocarcinoma.

    PubMed

    Lagergren, Jesper; Lagergren, Pernilla

    2013-01-01

    Answer questions and earn CME/CNE Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge. PMID:23818335

  3. Treatment of early-stage esophageal adenocarcinoma.

    PubMed

    Polish, Ariel; Mulcahy, Mary F

    2013-06-01

    Although T2,N0,M0 esophageal adenocarcinoma is grouped with other locoregional disease by NCCN, no consensus exists about how it should be treated. One of the inherent complexities of treating T2,N0,M0 esophageal adenocarcinoma is the inaccuracy of the clinical staging. In addition, conflicting evidence exists about whether neoadjuvant therapy adds any benefit to esophagectomy. A 52-year-old patient recently seen at the Robert H. Lurie Comprehensive Cancer Center illustrates the complexity of these issues. PMID:23744863

  4. Targeting chemokine pathways in esophageal adenocarcinoma

    PubMed Central

    Shrivastava, Makardhwaj S; Hussain, Zulfiqar; Giricz, Orsolya; Shenoy, Niraj; Polineni, Rahul; Maitra, Anirban; Verma, Amit

    2014-01-01

    Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets. PMID:25485576

  5. From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Wang, Rui-Hua

    2015-05-01

    The occurrence of gastroesophageal reflux disease is common in the human population. Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus, which is a complication of esophageal adenocarcinoma precancerous lesions. Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus. The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia, which is closely associated with the development of esophageal adenocarcinoma. However, the exact mechanism of injury is not completely understood. Various animal models of the developmental mechanisms of disease, and theoretical and clinical effects of drug treatment have been widely used in research. Recently, animal models employed in studies on gastroesophageal reflux injury have allowed significant progress. The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results. In this article, various modeling methods are reviewed, with discussion of the major findings on the developmental mechanism of Barrett's esophagus, which should help to develop better prevention and treatment strategies for Barrett's esophagus. PMID:25954094

  6. HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma.

    PubMed

    Hu, Yingchuan; Bandla, Santhoshi; Godfrey, Tony E; Tan, Dongfeng; Luketich, James D; Pennathur, Arjun; Qiu, Xing; Hicks, David G; Peters, Jeffrey H; Zhou, Zhongren

    2011-07-01

    The HER2 oncogene was recently reported to be amplified and overexpressed in esophageal adenocarcinoma. However, the relationship of HER2 amplification in esophageal adenocarcinoma with prognosis has not been well defined. The scoring systems for clinically evaluating HER2 in esophageal adenocarcinoma are not established. The aims of the study were to establish a HER2 scoring system and comprehensively investigate HER2 amplification and overexpression in esophageal adenocarcinoma and its precursor lesion. Using a tissue microarray, containing 116 cases of esophageal adenocarcinoma, 34 cases of Barrett's esophagus, 18 cases of low-grade dysplasia and 15 cases of high-grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and chromogenic in situ hybridization methods. The amplification frequency in an independent series of 116 esophageal adenocarcinoma samples was also analyzed using Affymetrix SNP 6.0 microarrays. In our studies, we have found that HER2 amplification does not associate with poor prognosis in total 232 esophageal adenocarcinoma patients by chromogenic in situ hybridization and high-density microarrays. We further confirm the similar frequency of HER2 amplification by chromogenic in situ hybridization (18%; 21 out of 116) and SNP 6.0 microarrays (16%, 19 out of 116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12% (14 out of 116) of esophageal adenocarcinoma and 7% (1 out of 15) of high-grade dysplasia. No HER2 amplification or overexpression was identified in Barrett's esophagus or low-grade dysplasia. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by chromogenic in situ hybridization than protein overexpression in esophageal adenocarcinoma (18 vs 12%). A modified two-step model for esophageal adenocarcinoma HER2 testing is recommended for clinical esophageal adenocarcinoma HER2 trial. PMID:21460800

  7. Association Between Markers of Obesity and Progression From Barrett’s Esophagus to Esophageal Adenocarcinoma Adenocarcinoma

    PubMed Central

    Duggan, Catherine; Onstad, Lynn; Hardikar, Sheetal; Blount, Patricia L; Reid, Brian J; Vaughan, Thomas L

    2013-01-01

    BACKGROUND & AIMS Individuals with Barrett’s esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EA). Obesity contributes to development of BE and its progression to cancer. We investigated the roles of obesity-induced hyperinsulinemia and dysregulation of adipokines in these processes. METHODS We measured fasting levels of glucose, insulin, leptin, and adiponectin in 392 patients enrolled in the Seattle BE Study. We calculated homeostatic model assessment (HOMA) scores (a measure of insulin sensitivity) and identified subjects with metabolic syndrome. We evaluated the association between these measures and risk of EA using Cox regression models adjusted for known risk factors. RESULTS Increasing HOMA scores were associated with increasing risk for EA; the strongest association was observed within the first 3 years after participants entered the study (hazard ratio (HR)=2.45; 95% confidence interval [CI], 1.43–4.1; Ptrend=.001). Leptin level was also significantly associated with increased risk of EA within 3 y (HR=2.51; 95% CI 1.09–5.81; Ptrend =0.03) and 6 y (HR=2.07; 95% CI 1.01–4.26; Ptrend=0.048) of baseline. The level of high molecular weight adiponectin had a non-linear inverse association with risk of EA; the strongest associations were observed in the second tertile (HR=0.34; 95% CI, 0.14–0.82). Metabolic syndrome was not associated with risk of EA. CONCLUSIONS Among patients with BE, increased levels of leptin and insulin resistance are associated with increased risk for EA, whereas increased level of high molecular weight adiponectin is inversely associated with EA. These biomarkers might be used to determine cancer risk among patients with BE. PMID:23466711

  8. Microbiome, innate Immunity, and esophageal adenocarcinoma

    PubMed Central

    Baghdadi, Jonathan; Chaudhary, Noami; Pei, Zhiheng; Yang, Liying

    2014-01-01

    With the development of culture-independent technique, a complex microbiome has been established and described in the distal esophagus. Over recent decades, the incidence of esophageal adenocarcinoma (EAC)—a relatively rare cancer with high mortality—has increased dramatically in the United States. Several studies documenting an altered microbiome associated with EAC and its precedents (i.e., Barrett’s esophagus and reflux esophagitis) suggest that dysbiosis may be contributing to carcinogenesis, potentially mediated by interactions with toll-like receptors. Investigations attempting to associate viruses, in particular human papilloma virus, with EAC have not been as consistent. Regardless, currently available data is cross-sectional and therefore cannot prove causal relationships. Prospectively, microbiome studies open a new avenue to the understanding of the etiology and pathogenesis of reflux disorders and EAC. PMID:25439272

  9. Dietary Risk Reduction Factors for the Barrett's Esophagus-Esophageal Adenocarcinoma Continuum: A Review of the Recent Literature

    PubMed Central

    Petrick, Jessica L.; Li, Nan; McClain, Kathleen M.; Steck, Susan E.

    2015-01-01

    Esophageal adenocarcinoma (EA) incidence is among the most rapidly increasing of any cancer type in the U.S., and prognosis is poor. Prevalence of the potential precursor lesion, Barrett's esophagus (BE), is also increasing. Candidates for safe and effective risk reduction strategies are needed, potentially including dietary components. In this qualitative review, we summarize recently published epidemiologic studies, in context of earlier work, on dietary intake and BE-EA outcomes. Potential cohort study/intervention trial candidates which could be increased to reduce BE-EA development include intake of: (1) fruits and vegetables; vegetables; fruit (EA only); (2) β-carotene and vitamins C and E; (3) folate (EA only); and (4) total fiber (EA only). Also, (5) red and processed meat intake could be targeted for dietary reduction/omission to reduce EA development. Few dietary constituents have been evaluated among EA patients to examine associations with mortality, thus interventions conducted among EA patients are premature. PMID:25750765

  10. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma

    PubMed Central

    Alexandre, Leo; Long, Elizabeth; Beales, Ian LP

    2014-01-01

    In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma (EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett’s esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the reflux-Barrett’s-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite by increasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett’s cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits. PMID:25400997

  11. Is Campylobacter to esophageal adenocarcinoma as Helicobacter is to gastric adenocarcinoma?

    PubMed

    Kaakoush, Nadeem O; Castaño-Rodríguez, Natalia; Man, Si Ming; Mitchell, Hazel M

    2015-08-01

    Esophageal adenocarcinoma develops through a cascade of cellular changes that shares similarities to the etiology of Helicobacter pylori-associated intestinal-type gastric adenocarcinoma. While host genetics and immune response have been implicated in the progression to esophageal adenocarcinoma, studies investigating esophageal microbial communities suggest that bacteria may also play an important role in driving the inflammation that leads to disease. Of these, emerging Campylobacter species have been found to be more prevalent and abundant in patients progressing through the esophageal adenocarcinoma cascade compared to controls. Given that these bacteria possess several virulence mechanisms such as toxin production, cellular invasion, and intracellular survival, emerging Campylobacter species should be investigated as etiological agents of the chronic esophageal inflammation that leads to cancer. PMID:25937501

  12. The Male Predominance in Esophageal Adenocarcinoma.

    PubMed

    Xie, Shao-Hua; Lagergren, Jesper

    2016-03-01

    The incidence of esophageal adenocarcinoma (EAC) has increased rapidly during the past 4 decades in many Western populations, including North America and Europe. The established etiological factors for EAC include gastroesophageal reflux and obesity, Helicobacter pylori infection, tobacco smoking, and consumption of fruit and vegetables. There is a marked male predominance of EAC with a male-to-female ratio in incidence of up to 9:1. This review evaluates the available literature on the reasons for the male predominance, particularly an update on epidemiologic evidence from human studies during the past decade. The striking sex difference does not seem to be explained by established risk factors, given that the prevalence of the etiological factors and the strengths of associations between these factors and EAC risk are similar between the sexes. Sex hormonal factors may play a role in the development of EAC; estrogenic exposures may prevent such development, whereas androgens might increase the risk of EAC. However, continuing research efforts are still needed to fully understand the reasons for the male predominance of EAC. PMID:26484704

  13. Endoscopic assessment and management of early esophageal adenocarcinoma

    PubMed Central

    Hammoud, Ghassan M; Hammad, Hazem; Ibdah, Jamal A

    2014-01-01

    Esophageal carcinoma affects more than 450000 people worldwide and the incidence is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence. Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus. These risk factors include chronic gastroesophageal reflux disease, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa. The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option. The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia. Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation, photodynamic therapy and cryoablation. Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion. Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor, positive lymph node and submucosal invasion. Surgical resection should be offered to patients with deep submucosal invasion. PMID:25132925

  14. Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

    ClinicalTrials.gov

    2015-12-18

    Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

  15. Simultaneous Esophageal Squamous Cell Carcinoma and Adenocarcinoma: A Case Report

    PubMed Central

    Maleki, Iradj; Shekarriz, Ramin; Nosrati, Anahita; Orang, Elahe

    2015-01-01

    Esophageal squamous cell carcinoma is a rather common cancer in northern Iran. Incidence of adenocarcinoma of esophagus has an increasing trend in Iran. Co-existence of both cancers in one patient is very rare. We report a middle age woman from northern Iran with a typical presentation of esophageal cancer, who was found to have a dual esophageal cancer. The disease was found in the advanced stage with pulmonary metastasis at the presentation. Palliative chemo-radiotherapy induced partial clinical response PMID:26609356

  16. Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus.

    PubMed

    Gharahkhani, Puya; Tung, Joyce; Hinds, David; Mishra, Aniket; Vaughan, Thomas L; Whiteman, David C; MacGregor, Stuart

    2016-02-15

    Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3-11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA. PMID:26704365

  17. Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus

    PubMed Central

    Gharahkhani, Puya; Tung, Joyce; Hinds, David; Mishra, Aniket; Vaughan, Thomas L.; Whiteman, David C.; MacGregor, Stuart

    2016-01-01

    Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3–11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA. PMID:26704365

  18. A Large-scale genetic association study of esophageal adenocarcinoma risk

    PubMed Central

    Liu, Chen-yu; Wu, Michael C.; Chen, Feng; Ter-Minassian, Monica; Asomaning, Kofi; Zhai, Rihong; Wang, Zhaoxi; Su, Li; Heist, Rebecca S.; Kulke, Matthew H.; Lin, Xihong; Liu, Geoffrey; Christiani, David C.

    2010-01-01

    The incidence of esophageal adenocarcinoma (EA) has been increasing rapidly, particularly among white males, over the past few decades in the USA. However, the etiology of EA and the striking male predominance is not fully explained by known risk factors. To identify susceptible genes for EA risk, we conducted a pathway-based candidate gene association study on 335 Caucasian EA cases and 319 Caucasian controls. A total of 1330 single-nucleotide polymorphisms (SNPs) selected from 354 genes were analyzed using an Illumina GoldenGate assay. The genotyped common SNPs include missense and exonic SNPs, SNPs within untranslated regions and 2 kb 5′ of the gene, and tagSNPs for genes with little functional information available. Logistic regression adjusted for potential confounders was used to assess the genetic effect of each SNP on EA risk. We also tested gene–gender interactions using the likelihood ratio tests. We found that the genetic variants in the apoptosis pathway were significantly associated with EA risk after correcting for multiple comparisons. SNPs of rs3127075 in Caspase-7 (CASP7) and rs4661636 in Caspase-9 (CASP9) genes that play a critical role in apoptosis were found to be associated with an increased risk of EA. A protective effect of SNP rs572483 in the progesterone receptor (PGR) gene was observed among women carrying the variant G allele [adjusted odds ratio (OR) = 0.19; 95% confidence interval (CI) = 0.08–0.46] but was not observed among men (adjusted OR = 1.38; 95% CI = 0.95–2.00). In conclusion, this study suggests that the genetic variants of CASP7 and CASP9 in the apoptosis pathway may be important predictive markers for EA susceptibility and that PGR in the sex hormone signaling pathway may be associated with the gender differences in EA risk. PMID:20453000

  19. Association between Polymorphisms in Cancer-Related Genes and Early Onset of Esophageal Adenocarcinoma123

    PubMed Central

    Wu, I-Chen; Zhao, Yang; Zhai, Rihong; Liu, Geoffrey; Ter-Minassian, Monica; Asomaning, Kofi; Su, Li; Liu, Chen-yu; Chen, Feng; Kulke, Matthew H; Heist, Rebecca S; Christiani, David C

    2011-01-01

    There is an increasing incidence of esophageal adenocarcinoma (EA) among younger people in the western populations. However, the association between genetic polymorphisms and the age of EA onset is unclear. In this study, 1330 functional/tagging single-nucleotide polymorphisms (SNPs) from 354 cancer-related genes were genotyped in 335 white EA patients. Twenty important SNPs that have the highest importance scores and lowest classification error rate were identified by the random forest algorithm to be associated with early onset of EA (age ? 55 years). Subsequent logistic regression analysis indicated that 10 SNPs (rs2070744 of NOS3, rs720321 of BCL2, rs17757541 of BCL2, rs11775256 of TNFRSF10A, rs1035142 of CASP8, rs2236302 of MMP14, rs4740363 of ABL1, rs696217 of GHRL, rs2445762 of CYP19A1, and rs11941492 of VEGFR2/KDR) were significantly associated with early onset of EA (?55 vs >55 years, all P < .05 after adjusting for co-variates and false discovery rate). Among them, five SNPs in the NOS3, BCL2, TNFRSF10A, and CASP8 genes were known to be involved in apoptosis processes. In Kaplan-Meier analyses, rs2070744 of NOS3, rs720321 of BCL2, and rs1035142 of CASP8 were also significantly associated with early onset of EA. Moreover, there was a higher risk of developing EA at a younger age when one had more risk genotypes. In conclusion, polymorphisms in cancer-related genes, especially those in the apoptotic pathway, play an important role in the development of younger-aged EA in a dose-response manner. PMID:21472143

  20. Review: Experimental models for Barrett's esophagus and esophageal adenocarcinoma

    PubMed Central

    Orlando, Roy C.; Chen, Xiaoxin

    2012-01-01

    Several different cell culture systems and laboratory animal models have been used over the years to study Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Most of the existing models have key differences with the human esophagus and complex pathogenesis of disease. None of the models offers an ideal system for the complex study of environmental exposure, genetic risk, and prevention strategies. In fact, different model systems may be required to answer different specific research questions about the pathogenesis of BE and EAC. Given the high mortality associated with EAC and the fact that current screening strategies miss most cases of EAC, advances in basic and translational science related to esophageal injury, repair, and carcinogenesis are clearly needed. This review describes several of the existing and potential model systems for BE and EAC with their benefits and disadvantages. PMID:22421618

  1. From reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    Wang, Rui-Hua

    2015-01-01

    The occurrence of gastroesophageal reflux disease is common in the human population. Almost all cases of esophageal adenocarcinoma are derived from Barrett’s esophagus, which is a complication of esophageal adenocarcinoma precancerous lesions. Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett’s esophagus. The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia, which is closely associated with the development of esophageal adenocarcinoma. However, the exact mechanism of injury is not completely understood. Various animal models of the developmental mechanisms of disease, and theoretical and clinical effects of drug treatment have been widely used in research. Recently, animal models employed in studies on gastroesophageal reflux injury have allowed significant progress. The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results. In this article, various modeling methods are reviewed, with discussion of the major findings on the developmental mechanism of Barrett’s esophagus, which should help to develop better prevention and treatment strategies for Barrett’s esophagus. PMID:25954094

  2. Effect of estrogen on growth and apoptosis in esophageal adenocarcinoma cells.

    PubMed

    Sukocheva, O A; Wee, C; Ansar, A; Hussey, D J; Watson, D I

    2013-08-01

    The epidemiology of esophageal adenocarcinoma demonstrates a strong gender bias with a sex ratio of 8-9:1 in favor of males. A potential explanation for this is that estrogen might protect against esophageal adenocarcinoma. Estrogen has previously been shown to stimulate apoptosis in esophageal squamous cancer cells. However, the effect of estrogen on esophageal adenocarcinoma cells has not been determined. We used immunoblotting analysis to determine the expression of estrogen receptors, cell adhesion marker E-cadherin, and proliferation marker Ki-67 in cell lines derived from esophageal adenocarcinoma (OE-19, OE-33) and Barrett's esophagus (QhTRT, ChTRT, GihTRT). Estrogen and selective estrogen receptor modulator (SERM)-dependent effects on cell growth were determined by the CellTiter-96 Aqueous Proliferation Assay. Apoptosis was determined by Annexin V/Propidium Iodide cell labeling and flow cytometry. We detected that physiological and supra-physiological concentrations of 17?-estradiol and SERM decreased cell growth in esophageal adenocarcinoma cells. In Barrett's esophagus cells (QhTRT, ChTRT), decreased growth was also detected in response to estrogen/SERM. The level of estrogen receptor expression in the cell lines correlated with the level of anti-growth effects induced by the receptor agonists. Flow cytometry analysis confirmed estrogen/SERM stimulated apoptosis in esophageal adenocarcinoma cells. Estrogen/SERM treatments were associated with a decrease in the expression of Ki-67 and an increase in E-cadherin expression in esophageal adenocarcinoma cells. This study suggests that esophageal adenocarcinoma and Barrett's esophagus cells respond to treatment with selective estrogen receptor ligands, resulting in decreased cell growth and apoptosis. Further research to explore potential therapeutic applications is warranted. PMID:23163347

  3. Precision Cancer Prevention of Esophageal Adenocarcinoma: A Lesson from Napoleon

    PubMed Central

    Vaughan, Thomas L.; Fitzgerald, Rebecca C.

    2015-01-01

    Summary A rapid and continuous rise in incidence of esophageal adenocarcinoma over the past four decades has been well documented in many developed countries across three continents. Among white males, who are in the highest risk demographic, incidence has risen 10-fold in the U.S. since the early 1970s. Incidence among males in the U.K. are among the highest in the world, and 50% higher than in the U.S. Unfortunately, treatments have not kept pace; unless their cancer is identified at a very early stage, most individuals will not survive a year after diagnosis. The beginnings of this widespread problem were first recognized over 25 years ago, yet rates have continued to rise against a backdrop of much improved understanding and management including the introduction of medical and surgical treatments aimed at reducing acid reflux, one of the most important risk factors; the availability of screening and surveillance programs for the precursor lesion Barrett’s metaplasia; and the development of endoscopic therapies for prevention or treatment of early invasive cancer. We estimate that only about 7% of the 10,000 cases of esophageal adenocarcinoma diagnosed annually in the U.S. are identified through current approaches to cancer control, and trace pathways by which the remaining 93% are “lost.” Based on emerging data on etiology and predictive factors coupled with new diagnostic tools, we suggest a five-tier strategy for prevention and control that begins with a wide population base and triages individuals into progressively higher risk strata, each with risk-appropriate prevention, screening and treatment options. PMID:25666644

  4. Dietary Factors and the Risks of Esophageal Adenocarcinoma and Barrett’s Esophagus

    PubMed Central

    Kubo, Ai; Corley, Douglas A.; Jensen, Christopher D.; Kaur, Rubinder

    2010-01-01

    Incidence rates for esophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastroesophageal reflux disease (GERD), obesity, and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not consistent with the demographic distribution of esophageal adenocarcinoma, which is substantially more common among whites and males than any other demographic groups. Numerous epidemiological studies have suggested associations between dietary factors and the risks of esophageal adenocarcinoma and its precursor, Barrett’s esophagus, though a comprehensive review is lacking. The main aim of the present review is to consider the evidence linking dietary factors with the risks of esophageal adenocarcinoma, Barrett’s esophagus, and the progression from Barrett’s esophagus to esophageal adenocarcinoma. The existing epidemiological evidence is strongest for an inverse relationship between intake of vitamin C, β-carotene, fruits and vegetables, particularly raw fruits and vegetables and dark-green, leafy and cruciferous vegetables, carbohydrates, fiber and iron and the risk of esophageal adenocarcinoma and Barrett’s esophagus. Patients at higher risk for Barrett’s esophagus and esophageal adenocarcinoma may benefit from increasing their consumption of fruits and vegetables and reducing their intake of red meat and other processed food items. Further research is needed to evaluate the relationship between diet and the progression of Barrett’s esophagus to esophageal adenocarcinoma. Evidence from cohort studies will help determine whether randomized chemoprevention trials are warranted for the primary prevention of Barrett’s esophagus or its progression to cancer. PMID:20624335

  5. LYN, a Key Gene From Bioinformatics Analysis, Contributes to Development and Progression of Esophageal Adenocarcinoma

    PubMed Central

    Liu, Dabiao

    2015-01-01

    Background Esophageal adenocarcinoma is a lethal malignancy whose incidence is rapidly growing in recent years. Previous reports suggested that Barretts esophagus (BE), which is represented by metaplasia-dysplasia-carcinoma transition, is regarded as the premalignant lesion of esophageal neoplasm. However, our knowledge about the development of esophageal adenocarcinoma is still very limited. Material/Methods In order to acquire better understanding about the pathological mechanisms in this field, we obtained gene profiling data on BE, esophageal adenocarcinoma patients, and normal controls from the Gene Expression Omnibus (GEO) database. Bioinformatics analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were conducted. Results Our results revealed that several pathways, such as the wound healing, complement, and coagulation pathways, were closely correlated with cancer development and progression. The mitogen-activated protein kinase (MAPK) pathway was discovered to be responsible for the predisposition stage of cancer; while response to stress, cytokine-cytokine receptor interaction, nod-like receptor signaling pathway, and ECM-receptor interaction were chief contributors of cancer progression. More importantly, we discovered in this study that LYN was a critical gene. It was found to be the key nodule of several significant biological networks, which suggests its close correlation with cancer initiation and progression. Conclusions These results provided more information on the mechanisms of esophageal adenocarcinoma, which enlightened our way to the clinical discovery of novel therapeutic makers for conquering esophageal cancer. Keywords: esophageal adenocarcinoma; LYN; Go analysis; KEGG pathway. PMID:26708841

  6. Expression and Effect of Inhibition of the Ubiquitin-Conjugating Enzyme E2C on Esophageal Adenocarcinoma1

    PubMed Central

    Lin, Jules; Raoof, Duna A; Wang, Zhuwen; Lin, Mu-Yen; Thomas, Dafydd G; Greenson, Joel K; Giordano, Thomas J; Orringer, Mark B; Chang, Andrew C; Beer, David G; Lin, Lin

    2006-01-01

    Abstract Ubiquitin-dependent proteolysis of cyclins plays a critical role in cell cycle progression and tumorigenesis. We examined the expression of ubiquitin-conjugating enzyme E2C (UBE2C) during progression from Barrett's metaplasia to esophageal adenocarcinoma (EA) and the effects of targeting this enzyme on EA-derived cell lines. Using oligonucleotide microarrays UBE2C expression was elevated in 73% (11 of 15) of EAs relative to Barrett's metaplasia. Tissue microarray showed elevated UBE2C in 70% (7 of 10) of dysplastic samples and in 87% (58 of 67) of tumors relative to metaplastic samples. Transfection of dominant-negative UBE2C into Seg-1 cells decreased proliferation (P = .04) and increased mitotic arrest compared to vector controls (63.5% vs 6.8%; P < .001). Transfection of UBE2C small interfering RNA also caused inhibiton of cell proliferation and distortion of the cell cycle, with maximal increase of G2 cells (155% of mock cells) at 72 hours and of S-phase cells (308% of mock cells) at 24 hours. Treatment of Seg-1 cells with the proteasome inhibitor MG-262 (1 nM-1 µM) showed decreased proliferation (P = .02). EA-derived cells expressing UBE2C are sensitive to treatment with MG-262 and to silencing of UBE2C, suggesting that patients with EAs overexpressing UBE2C may benefit from agents targeting this ubiquitin-conjugating enzyme. PMID:17217624

  7. MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium

    PubMed Central

    Buas, Matthew F.; Onstad, Lynn; Levine, David M.; Risch, Harvey A.; Chow, Wong-Ho; Liu, Geoffrey; Fitzgerald, Rebecca C.; Bernstein, Leslie; Ye, Weimin; Bird, Nigel C.; Romero, Yvonne; Casson, Alan G.; Corley, Douglas A.; Shaheen, Nicholas J.; Wu, Anna H.; Gammon, Marilie D.; Reid, Brian J.; Hardie, Laura J.; Peters, Ulrike; Whiteman, David C.; Vaughan, Thomas L.

    2015-01-01

    Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P<0.05) of 29 SNPs with EA risk, and 25 SNPs with BE risk, were observed. None remained significant after correction for multiple comparisons (FDR q>0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk. PMID:26039359

  8. [A Case of Synchronous Multiple Esophageal Cancers Composed of Squamous Cell Carcinoma and Barrett's Adenocarcinoma].

    PubMed

    Kobayashi, Toshiyuki; Shiozaki, Atsushi; Fujiwara, Hitoshi; Konishi, Hirotaka; Arita, Tomohiro; Kosuga, Toshiyuki; Morimura, Ryo; Murayama, Yasutoshi; Komatsu, Shuhei; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Okamoto, Kazuma; Otsuji, Eigo

    2015-11-01

    A 67-year-old man was admitted to our hospital for treatment for multiple superficial esophageal cancers. Screening upper gastrointestinal endoscopy examination revealed a superficial squamous cell carcinoma (SCC) at the middle thoracic esophagus and Barrett's epithelium and a superficial adenocarcinoma at the abdominal esophagus. We performed a subtotal esophagectomy with gastric tube reconstruction via the retrosternal route. Pathological examination revealed a Barrett's adenocarcinoma at the abdominal esophagus. Esophageal cancer is thought to be a multicentric disease, and we sometimes find multiple esophageal cancers. In Japan, most cases of multiple esophageal cancers are composed of SCCs, and the occurrence of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma is rare. In contrast, the number of the patients with Barrett's esophagus is increasing, and the number of the patients with Barrett's adenocarcinoma also seems to be on the rise. Therefore, it is important be aware of the possibility of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma while making diagnoses. PMID:26805207

  9. Translational research on esophageal adenocarcinoma: from cell line to clinic.

    PubMed

    Boonstra, J J; Tilanus, H W; Dinjens, W N M

    2015-01-01

    Human esophageal adenocarcinoma (EAC) cell lines have made a substantial contribution to elucidating mechanisms of carcinogenesis and drug discovery. Model research on EAC relies almost entirely on a relatively small set of established tumor cell lines because appropriate animal models are lacking. Nowadays, more than 20% of all fundamental translational research studies regarding EAC are partially or entirely based on these cell lines. The ready availability of these cell lines to investigators worldwide have resulted in more than 250 publications, including many examples of important biomedical discoveries. The high genomic similarities (but certainly not completely identical) between the EAC cell lines and their original tumors provide rational for their use. Recently, in a collaborative effort all available EAC cell lines have been verified resulting in the establishment of a reliable panel of 10 EAC cell lines. It could be expected that the value of these cell lines increases as unlimited source of tumor material because new biomedical techniques require more tumor cells and the supply of viable tumor cells is diminishing because of neoadjuvant chemo(radio)therapy of patients with EAC. Here, we review the history of the EAC cell lines and their utility in translational research and biomedical discovery. PMID:23795680

  10. Early onset esophageal adenocarcinoma: a distinct molecular entity?

    PubMed Central

    van Nistelrooij, Anna M.J.; van Marion, Ronald; Biermann, Katharina; Spaander, Manon C.W.; van Lanschot, J. Jan B.; Wijnhoven, Bas P.L.; Dinjens, Winand N.M.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is typically diagnosed in elderly with a median age of 68 years. The incidence of EAC has been rising over the last decades, also among young adults. The aim of the study was to investigate whether early onset EAC is a distinct molecular entity. To identify early onset EACs, the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA) was searched. Twenty-eight tumors of patients aged ≤40 years were selected and matched with 27 tumors of patients aged ≥68 years. DNA was isolated from surgically resected specimen and sequenced on the Ion Torrent Personal Genome Machine with the Ion AmpliSeq Cancer Panel. No differences in mutational load between early onset and conventional EACs were observed (P=0.196). The most frequently mutated genes were TP53 (73%) and P16 (16%). Additional mutations in early onset EACs occurred exclusively in: APC, CDH1, CTNNB1, FGFR2, and STK11. In the conventional EACs additional mutations were exclusively identified in: ABL1, FBXW7, GNA11, GNAS, KRAS, MET, SMAD4, and VHL. Additional mutations besides TP53 and P16 seem to occur in different genes related to cell fate pathways for early onset EACs, while the additional mutations in conventional EACs are related to survival pathways. PMID:26973859

  11. LYN, a Key Gene From Bioinformatics Analysis, Contributes to Development and Progression of Esophageal Adenocarcinoma.

    PubMed

    Liu, Dabiao

    2015-01-01

    BACKGROUND Esophageal adenocarcinoma is a lethal malignancy whose incidence is rapidly growing in recent years. Previous reports suggested that Barrett's esophagus (BE), which is represented by metaplasia-dysplasia-carcinoma transition, is regarded as the premalignant lesion of esophageal neoplasm. However, our knowledge about the development of esophageal adenocarcinoma is still very limited. MATERIAL AND METHODS In order to acquire better understanding about the pathological mechanisms in this field, we obtained gene profiling data on BE, esophageal adenocarcinoma patients, and normal controls from the Gene Expression Omnibus (GEO) database. Bioinformatics analyses, including Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were conducted. RESULTS Our results revealed that several pathways, such as the wound healing, complement, and coagulation pathways, were closely correlated with cancer development and progression. The mitogen-activated protein kinase (MAPK) pathway was discovered to be responsible for the predisposition stage of cancer; while response to stress, cytokine-cytokine receptor interaction, nod-like receptor signaling pathway, and ECM-receptor interaction were chief contributors of cancer progression. More importantly, we discovered in this study that LYN was a critical gene. It was found to be the key nodule of several significant biological networks, which suggests its close correlation with cancer initiation and progression. CONCLUSIONS These results provided more information on the mechanisms of esophageal adenocarcinoma, which enlightened our way to the clinical discovery of novel therapeutic makers for conquering esophageal cancer. PMID:26708841

  12. Cytoplasmic Overexpression of CD95L in Esophageal Adenocarcinoma Cells Overcomes Resistance to CD95-Mediated Apoptosis1

    PubMed Central

    Watson, Gregory A; Naran, Sanjay; Zhang, Xinglu; Stang, Michael T; Queiroz de Oliveira, Pierre E; Hughes, Steven J

    2011-01-01

    Introduction The CD95/CD95L pathway plays a critical role in tissue homeostasis and immune system regulation; however, the function of this pathway in malignancy remains poorly understood. We hypothesized that CD95L expression in esophageal adenocarcinoma confers advantages to the neoplasm other than immune privilege. Methods CD95L expression was characterized in immortalized squamous esophagus (HET-1A) and Barrett esophagus (BAR-T) cells; adenocarcinoma cell lines FLO-1, SEG-1, and BIC-1, and MDA468 (- control); and KFL cells (+ control). Analyses included reverse transcription-polymerase chain reaction, immunoblots of whole cell and secretory vesicle lysates, FACScan analysis, laser scanning confocal microscopy of native proteins and fluorescent constructs, and assessment of apoptosis and ERK1/2 pathways. Results Cleaved, soluble CD95L is expressed at both the RNA and protein levels in these cell lines derived from esophageal adenocarcinoma and other human tissues. CD95L was neither trafficked to the cell membrane nor secreted into the media or within vesicles, rather the protein seems to be sequestered in the cytoplasm. CD95 and CD95L colocalize by immunofluorescence, but an interaction was not proven by immunoprecipitation. Overexpression of CD95L in the adenocarcinoma cell lines induced robust apoptosis and, under conditions of pan-caspase inhibition, resulted in activation of ERK signaling. Conclusions CD95L localization in EA cells is inconsistent with the conference of immune privilege and is more consistent with a function that promotes tumor growth through alternative CD95 signaling. Reduced cell surface expression of CD95 affects cell sensitivity to extracellular apoptotic signals more significantly than alterations in downstream modulators of apoptosis. PMID:21390183

  13. IGFBP2 modulates the chemoresistant phenotype in esophageal adenocarcinoma

    PubMed Central

    Myers, Amy L.; Lin, Lin; Nancarrow, Derek J.; Wang, Zhuwen; Ferrer-Torres, Daysha; Thomas, Dafydd G.; Orringer, Mark B.; Lin, Jules; Reddy, Rishindra M.; Beer, David G.; Chang, Andrew C.

    2015-01-01

    Esophageal adenocarcinoma (EAC) patients commonly present with advanced stage disease and demonstrate resistance to therapy, with response rates below 40%. Understanding the molecular mechanisms of resistance is crucial for improvement of clinical outcomes. IGFBP2 is a member of the IGFBP family of proteins that has been reported to modulate both IGF and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types. In this study, high IGFBP2 expression was observed in a subset of primary EACs and was found to be significantly higher in patients with shorter disease-free intervals as well as in treatment-resistant EACs as compared to chemonaive EACs. Modulation of IGFBP2 expression in EAC cell lines promoted cell proliferation, migration and invasion, implicating a role in the metastatic potential of these cells. Additionally, knockdown of IGFBP2 sensitized EAC cells to cisplatin in a serum-dependent manner. Further in vitro exploration into this chemosensitization implicated both the AKT and ERK pathways. Silencing of IGFBP2 enhanced IGF1-induced immediate activation of AKT and reduced cisplatin-induced ERK activation. Addition of MEK1/2 (selumetinib or trametinib) or AKT (AKT Inhibitor VIII) inhibitors enhanced siIGFBP2-induced sensitization of EAC cells to cisplatin. These results suggest that targeted inhibition of IGFBP2 alone or together with either the MAPK or PI3K/AKT signaling pathway in IGFBP2-overexpressing EAC tumors may be an effective approach for sensitizing resistant EACs to standard neoadjuvant chemotherapy. PMID:26317790

  14. Tumor-specific apoptotic gene targeting overcomes radiation resistance in esophageal adenocarcinoma

    SciTech Connect

    Chang, Joe Y. . E-mail: jychang@mdanderson.org; Zhang Xiaochun; Komaki, Ritsuko; Cheung, Rex; Fang Bingliang

    2006-04-01

    Purpose: To overcome radiation resistance in esophageal adenocarcinoma by tumor-specific apoptotic gene targeting using tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Methods and Materials: Adenoviral vector Ad/TRAIL-F/RGD with a tumor-specific human telomerase reverse transcription promoter was used to transfer TRAIL gene to human esophageal adenocarcinoma and normal human lung fibroblastic cells (NHLF). Activation of apoptosis was analyzed by Western blot, fluorescent activated cell sorting, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate labeling (TUNEL) assay. A human esophageal adenocarcinoma mouse model was treated with intratumoral injections of Ad/TRAIL-F/RGD plus local radiotherapy. Results: The combination of Ad/TRAIL-F/RGD and radiotherapy increased the cell-killing effect in all esophageal adenocarcinoma cell lines but not in NHLF cells. This combination also significantly reduced clonogenic formation (p < 0.05) and increased sub-G1 deoxyribonucleic acid accumulation in cancer cells (p < 0.05). Activation of apoptosis by Ad/TRAIL-F/RGD plus radiotherapy was demonstrated by activation of caspase-9, caspase-8, and caspase-3 and cleaved poly (adenosine diphosphate-ribose) polymerase in vitro and TUNEL assay in vivo. Combined Ad/TRAIL-F/RGD and radiotherapy dramatically inhibited tumor growth and prolonged mean survival in the esophageal adenocarcinoma model to 31.6 days from 16.7 days for radiotherapy alone and 21.5 days for Ad/TRAIL-F/RGD alone (p < 0.05). Conclusions: The combination of tumor-specific TRAIL gene targeting and radiotherapy enhances the effect of suppressing esophageal adenocarcinoma growth and prolonging survival.

  15. Effect of aspirin treatment on the prevention of esophageal adenocarcinoma in a rat experimental model.

    PubMed

    Esquivias, Paula; Cebrián, Carmelo; Morandeira, Antonio; Santander, Sonia; Ortego, Javier; García-González, María Asunción; Lanas, Angel; Piazuelo, Elena

    2014-06-01

    Aspirin has been proposed in recent years as a candidate for chemoprevention of adenocarcinoma in patients with Barrett's esophagus. The aim of the present study was to evaluate the effect of acetylsalicylic acid (ASA) in an experimental model of esophageal adenocarcinoma. An animal model of gastroenteroesophageal reflux was established using Wistar rats undergoing esophagojejunostomy with gastric preservation. Following surgery, rats were divided into three groups: i) control (vehicle); ii) ASA 50 mg/kg/day; and iii) ASA 5 mg/kg/day. Four months after surgery, the surviving animals were sacrificed and the rat esophagi were assessed for histological and biochemical [prostaglandin E2 (PGE2) and lipoxin A4 (LXA4 ) levels] analysis. As in the control rats, those receiving aspirin treatment showed no decrease in inflammation grade, extent of ulcerated esophageal mucosa, length of intestinal metaplasia in continuity with anastomosis, presence of intestinal metaplasia beyond anastomosis, severity of dysplasia or incidence of adenocarcinoma. In contrast, aspirin-treated rats showed decreased esophageal tissue levels of PGE2 and increased LXA4, significantly in the high-dose aspirin group (p=0.008 and p=0.01, respectively). In this rat model of gastroesophageal reflux, the administration of aspirin modified esophageal tissue levels of PGE2 and LXA4, but was not effective in preventing the development of esophageal adenocarcinoma. PMID:24737143

  16. Physical activity is associated with reduced risk of esophageal cancer, particularly esophageal adenocarcinoma: a systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background Physical activity has been inversely associated with risk of several cancers. We performed a systematic review and meta-analysis to evaluate the association between physical activity and risk of esophageal cancer (esophageal adenocarcinoma [EAC] and/or esophageal squamous cell carcinoma [ESCC]). Methods We conducted a comprehensive search of bibliographic databases and conference proceedings from inception through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and esophageal cancer risk. Summary adjusted odds ratio (OR) estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Results The analysis included 9 studies (4 cohort, 5 case–control) reporting 1,871 cases of esophageal cancer among 1,381,844 patients. Meta-analysis demonstrated that the risk of esophageal cancer was 29% lower among the most physically active compared to the least physically active subjects (OR, 0.71; 95% CI, 0.57-0.89), with moderate heterogeneity (I2 = 47%). On histology-specific analysis, physical activity was associated with a 32% decreased risk of EAC (4 studies, 503 cases of EAC; OR, 0.68; 95% CI, 0.55-0.85) with minimal heterogeneity (I2 = 0%). There were only 3 studies reporting the association between physical activity and risk of ESCC with conflicting results, and the meta-analysis demonstrated a null association (OR, 1.10; 95% CI, 0.21-5.64). The results were consistent across study design, geographic location and study quality, with a non-significant trend towards a dose–response relationship. Conclusions Meta-analysis of published observational studies indicates that physical activity may be associated with reduced risk of esophageal adenocarcinoma. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of EAC. PMID:24886123

  17. Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

    ClinicalTrials.gov

    2016-05-31

    Adenocarcinoma of the Gastroesophageal Junction; Esophageal Adenocarcinoma; Stage IB Esophageal Cancer; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer

  18. Epidermal Growth Factor Receptor Kinase Domain Mutations in Esophageal and Pancreatic Adenocarcinomas

    PubMed Central

    Kwak, Eunice L.; Jankowski, Janusz; Thayer, Sarah P.; Lauwers, Gregory Y.; Brannigan, Brian W.; Harris, Patricia L.; Okimoto, Ross A.; Haserlat, Sara M.; Dris coll, David R.; Ferry, David; Muir, Beth; Settleman, Jeff; Fuchs, Charles S.; Kulke, Matthew H.; Ryan, David P.; Clark, Jeff W.; Sgroi, Dennis C.; Haber, Daniel A.; Bell, Daphne W.

    2013-01-01

    Purpose Specific activating mutations within the epidermal growth factor receptor (EGFR) identify a subset of non – small cell lung cancers with dramatic sensitivity to the specific tyrosine kinase inhibitors (TKI), gefitinib and erlotinib. Despite the abundant expression of EGFR protein in a broad range of epithelial cancers, EGFR mutations have not been reported in a substantial fraction of other cancers. Given recent reports of TKI-responsive cases of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers. Experimental Design We sequenced exons 18 to 21 of EGFR from 21cases of Barrett's esophagus, 5 cases of high-grade esophageal dysplasia, 17 cases of esophageal adenocarcinoma, and 55 cases of pancreatic adenocarcinoma. Subsets of esophageal (n = 7) and pancreatic cancer cases (n = 5) were obtained from patients who were subsequently treated with gefitinib or erlotinib-capecitabine, respectively. Results Mutations of EGFR were identified in two esophageal cancers (11.7%), three cases of Barrett's esophagus (14.2%), and two pancreatic cancers (3.6%). The mutations consisted of the recurrent missense L858R and in-frame deletion delE746-A750, previously characterized as activating EGFR mutations in non – small cell lung cancer. We also identified the TKI drug resistance – associated EGFR T790M mutation in an untreated case of Barrett's esophagus and the corresponding adenocarcinoma. Conclusion The presence of activating mutations within EGFR in both esophageal and pancreatic adenocarcinomas defines a previously unrecognized subset of gastrointestinal tumors in which EGFR signaling may play an important biological role. EGFR mutations in premalignant lesions of Barrett's esophagus also point to these as an early event in transformation of the esophageal epithelium. The role of genotype-directed TKI therapy should be tested in prospective clinical trials. PMID:16857803

  19. Comparison of prevalence and resection rates in patients with esophageal squamous cell carcinoma and adenocarcinoma.

    PubMed

    Heitmiller, R F; Sharma, R R

    1996-07-01

    Since 1987 we have observed a predominance of adenocarcinoma in patients undergoing esophagectomy because of carcinoma at our institution. To discover whether this observation represented an actual change in the prevalence of adenocarcinoma, the Johns Hopkins Hospital pathology records were reviewed for the years 1959 to 1994. Overall, esophageal squamous cell carcinoma was the most common histologic type with 817 cases identified versus 284 cases of adenocarcinoma. The number of patients with squamous cell carcinoma rose slowly from 1959 to 1992 but since 1992 has decreased. Whereas adenocarcinoma was uncommon before 1978, its frequency has since increased markedly, exceeding that of squamous cell carcinoma in 1994. The number of patients with adenocarcinoma who underwent surgical resection has equaled or exceeded the number of those treated nonoperatively for all recorded years. Therefore the predominance of adenocarcinoma in patients undergoing esophageal resection for carcinoma appears to result from two factors: an overall increase in the prevalence of adenocarcinoma since 1978 and an increased likelihood of resection for patients with these tumors. PMID:8691857

  20. Advances in the management of Barrett’s esophagus and early esophageal adenocarcinoma

    PubMed Central

    Singh, Ajaypal; Chak, Amitabh

    2015-01-01

    The incidence of esophageal adenocarcinoma (EAC) has markedly increased in the United States over the last few decades. Barrett’s esophagus (BE) is the most significant known risk factor for this malignancy. Theoretically, screening and treating early BE should help prevent EAC but the exact incidence of BE and its progression to EAC is not entirely known and cost-effectiveness studies for Barrett’s screening are lacking. Over the last few years, there have been major advances in our understanding of the epidemiology, pathogenesis and endoscopic management of BE. These developments focus on early recognition of advanced histology and endoscopic treatment of high-grade dysplasia. Advanced resection techniques now enable us to endoscopically treat early esophageal cancer. In this review, we will discuss these recent advances in diagnosis and treatment of Barrett’s esophagus and early esophageal adenocarcinoma. PMID:26486568

  1. Overexpression of claudin proteins in esophageal adenocarcinoma and its precursor lesions.

    PubMed

    Montgomery, Elizabeth; Mamelak, Adam J; Gibson, Michael; Maitra, Anirban; Sheikh, Salwa; Amr, Samir S; Yang, Stephen; Brock, Malcolm; Forastiere, Arlene; Zhang, Shengle; Murphy, Kathleen M; Berg, Karin D

    2006-03-01

    Claudins are components of tight junctions important in intercellular barriers and cell polarity. The authors identified upregulation of Claudins 3, 4, and 7 in gastric adenocarcinoma using Affymetrix U-133 oligonucleotide microarrays and immunohistochemistry (IHC). While normal gastric mucosa lacked Claudin 3, 4, and 7 expression, intestinal metaplasia and dysplasia showed these proteins. The authors hypothesized that Claudins would be similarly overexpressed in Barrett's esophagus (BE)/adenocarcinoma. Claudins 3, 4, and 7 gene expression was analyzed by Affymetrix U-133 microarrays in three esophageal adenocarcinomas, one case of BE, and three normal esophagi. IHC validation was performed using tissue microarrays constructed from esophageal resection specimens containing squamous (44 cases), gastric (40 cases), and non-dysplastic BE (16 cases), low-grade and high-grade dysplasia (16 and 26 cases), adenocarcinoma (58 cases), and nodal metastases (27 cases). IHC staining was scored semiquantitatively (0+ to 4+). By microarray analysis, Claudin 3 showed a marked increase in mRNA expression compared with normal esophagus (approximately 100-fold). Claudins 4 and 7 were modestly increased (2.2- and 1.3-fold). By IHC, Claudin 3 expression was 1+ in most (>95%) normal squamous or gastric tissues and 2+ to 4+ in more than 80% of high-grade dysplasia, adenocarcinoma, and metastases specimens. Claudin 4 protein expression was 2+ or less in most squamous and gastric mucosa (>90%) but 3+ or 4+ in BE, low- and high-grade dysplasia, adenocarcinoma, and metastases specimens (>90%). Claudin 7 expression was minimal in squamous and gastric mucosa but strong (3+ to 4+) in BE and low-grade dysplasia. In high-grade dysplasia, adenocarcinoma, and metastases, Claudin 7 was less intense, with 60% to 70% staining 3+ or 4+ and 30% to 40% staining weakly (1+ or 2+). The findings suggest that alterations in Claudin proteins are an early event in tumorigenesis and may provide targets for diagnosis and directed therapy for esophageal adenocarcinoma and its precursors. PMID:16540726

  2. Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells

    PubMed Central

    Cao, Weibiao

    2016-01-01

    Mechanisms of the progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK) inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA. PMID:26901778

  3. Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of Helicobacter pylori infection status.

    PubMed

    Zhai, Rihong; Wei, Yongyue; Su, Li; Liu, Geoffrey; Kulke, Mathew H; Wain, John C; Christiani, David C

    2015-01-01

    Cell free circulating microRNAs (cfmiRNAs) have been recognized as robust and stable biomarkers of cancers. However, little is known about the prognostic significance of cfmiRNAs in esophageal adenocarcinoma (EA). In this study, we explored whether specific cfmiRNA profiles could predict EA prognosis and whether Helicobacter pylori (HP) infection status could influence the association between cfmiRNAs and EA survival outcome. We profiled 1075 miRNAs in pooled serum samples from 30 EA patients and 30 healthy controls. The most relevant cfmiRNAs were then assessed for their associations with EA survival in an independent cohort of 82 patients, using Log-rank test and multivariate Cox regression models. Quantitative real-time PCR (qRT-PCR) was used for cfmiRNA profiling. HP infection status was determined by immunoblotting assay. We identified a panel of 18 cfmiRNAs that could distinguish EA patients from healthy subjects (P = 3.0E-12). In overall analysis and in HP-positive subtype patients, no cfmiRNA was significantly associated with EA prognosis. In HP-negative patients, however, 15 cfmiRNAs were significantly associated with overall survival (OS) (all P < 0.05). A combined 2-cfmiRNA (low miR-3935 and high miR-4286) risk score was constructed; that showed greater risk for worse OS (HR = 2.22, P = 0.0019) than individual cfmiRNA alone. Patients with high-risk score had >10-fold increased risk of death than patients with low risk score (P = 0.0302; HR = 10.91; P = 0.0094). Our findings suggest that dysregulated cfmiRNAs may contribute to EA survival outcome and HP infection status may modify the association between cfmiRNAs and EA survival. PMID:25381453

  4. Infrared light-absorbing gold/gold sulfide nanoparticles induce cell death in esophageal adenocarcinoma

    PubMed Central

    Li, Yan; Gobin, Andre M; Dryden, Gerald W; Kang, Xinqin; Xiao, Deyi; Li, Su Ping; Zhang, Guandong; Martin, Robert CG

    2013-01-01

    Gold nanoparticles and near infrared-absorbing light are each innocuous to tissue but when combined can destroy malignant tissue while leaving healthy tissue unharmed. This study investigated the feasibility of photothermal ablation therapy for esophageal adenocarcinoma using chitosan-coated gold/gold sulfide (CS-GGS) nanoparticles. A rat esophagoduodenal anastomosis model was used for the in vivo ablation study, and three human esophageal cell lines were used to study the response of cancer cells and benign cells to near infrared light after treatment with CS-GGS. The results indicate that both cancerous tissue and cancer cells took up more gold nanoparticles and were completely ablated after exposure to near infrared light. The benign tissue and noncancerous cells showed less uptake of these nanoparticles, and remained viable after exposure to near infrared light. CS-GGS nanoparticles could provide an optimal endoluminal therapeutic option for near infrared light ablation of esophageal cancer. PMID:23818775

  5. Role of epigenetic alterations in the pathogenesis of Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Agarwal, Archana; Polineni, Rahul; Hussein, Zulfiqar; Vigoda, Ivette; Bhagat, Tushar D; Bhattacharyya, Sanchari; Maitra, Anirban; Verma, Amit

    2012-01-01

    Barrett's esophagus, a pre-malignant condition that can lead to esophageal adenocarcinoma, is characterized by histological changes in the normal squamous epithelium of the esophagus. Numerous molecular changes occur during the multistage conversion of Barrett's metaplasia to dysplasia and frank adenocarcinoma. Epigenetic changes, especially changes in DNA methylation are widespread during this process. Aberrant DNA methylation has been shown to occur at promoters of tumor suppressor genes, adhesion molecules and DNA repair genes during Barrett's esophagus. These epigenetic alterations can be used as molecular biomarkers for risk stratification and early detection of esophageal adenocarcinoma. We also show that genome wide analysis of methylation surprisingly reveals that global hypomethylation and not hypermethylation is the dominant change during Barrett's metaplasia. The transformation of Barrett's esophagus to frank adenocarcinoma is in turn characterized by much smaller wave of selective promoter hypermethylation. These studies reveal many novel, potential targets for new therapies and illustrate the utility of incorporating these epigenetic changes as biomarkers during endoscopic surveillance interval for patients with Barrett's esophagus. PMID:22808291

  6. Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma

    PubMed Central

    Le Bras, Gregoire F.; Koumangoye, Rainelli B.; Romero-Morales, Alejandra I.; Quast, Laura L.; Zaika, Alexander I.; El-Rifai, Wael; Andl, Thomas; Andl, Claudia D.

    2015-01-01

    TGFβ signaling has been implicated in the metaplasia from squamous epithelia to Barrett's esophagus and, ultimately, esophageal adenocarcinoma. The role of the family member Activin A in Barrett's tumorigenesis is less well established. As tumorigenesis is influenced by factors in the tumor microenvironment, such as fibroblasts and the extracellular matrix, we aimed to determine if epithelial cell-derived Activin affects initiation and progression differently than Activin signaling stimulation from a mimicked stromal source. Using Barrett's esophagus cells, CPB, and the esophageal adenocarcinoma cell lines OE33 and FLO-1, we showed that Activin reduces colony formation only in CPB cells. Epithelial cell overexpression of Activin increased cell migration and invasion in Boyden chamber assays in CPB and FLO-1 cells, which exhibited mesenchymal features such as the expression of the CD44 standard form, vimentin, and MT1-MMP. When grown in organotypic reconstructs, OE33 cells expressed E-cadherin and Keratin 8. As mesenchymal characteristics have been associated with the acquisition of stem cell-like features, we analyzed the expression and localization of SOX9, showing nuclear localization of SOX9 in esophageal CPB and FLO-1 cells. In conclusion, we show a role for autocrine Activin signaling in the regulation of colony formation, cell migration and invasion in Barrett's tumorigenesis. PMID:26447543

  7. Esophageal adenocarcinoma in a 53-year-old mata mata turtle (Chelus fimbriatus).

    PubMed

    Lombardini, Eric D; Desoutter, Anais V; Montali, Richard J; Del Piero, Fabio

    2013-09-01

    A 53-yr-old male captive mata mata turtle (Chelus fimbriatus) was examined following sudden death. The animal was in good nutritional, muscular and postmortem condition. The esophageal wall was circumferentially expanded by a discrete, oblong, irregular, tan, and soft contiguous glandlike structure. Histologically, the mass comprised uneven, sometimes cavitated islands of polygonal neoplastic cells consistent with an esophageal adenocarcinoma. In addition, peripheral to the mass, there was glandular epithelial hyperplasia, dysplasia, and multifocal heterophilic and lymphohistiocytic adenitis. Neoplastic cells expressed pancytokeratins; however, they demonstrated no immunoreactivity to vimentin, chromogranin, synaptophysin, and thyroglobulin. Additional findings included multifocal to coalescing areas of cortical fibrosis and membranous glomerulonephritis affecting both kidneys, and a focal hepatocellular adenoma. PMID:24063112

  8. Bile Acid Reflux Contributes To Development of Esophageal Adenocarcinoma Via Activation Of Phosphatidylinositol-Specific Phospholipase Cγ2 And NADPH Oxidase NOX5-S

    PubMed Central

    Hong, Jie; Behar, Jose; Wands, Jack; Resnick, Murray; Wang, Li Juan; DeLellis, Ronald A.; Lambeth, David; Cao, Weibiao

    2009-01-01

    Gastroesophageal reflux disease complicated by Barrett’s esophagus (BE) is a major risk factor for esophageal adenocarcinoma (EA). However, the mechanisms of the progression from BE to EA are not fully understood. Besides acid reflux, bile acid reflux may also play an important role in the progression from BE to EA. In this study we examined the role of phosphatidylinositol-specific phospholipase C (PI-PLC) and a novel NADPH oxidase NOX5-S in bile acid-induced in cell proliferation. We found that taurodeoxycholic acid (TDCA) significantly increased NOX5-S expression, H2O2 production and cell proliferation in EA cells. The TDCA-induced increase in cell proliferation was significantly reduced by U73122, an inhibiter of PI-PLC. PI-PLCβ1, β3, β4, γ1 and γ2, but not β2 and δ1 were detectable in FLO cells by Western blot analysis. Knockdown of PI-PLCγ2 or ERK-2 MAP kinase with siRNAs significantly decreased TDCA-induced increase in NOX5-S expression, H2O2 production and cell proliferation. In contrast, knockdown of PI-PLC β1, β3, β4, γ1 or ERK-1 MAP kinase had no significant effect. TDCA significantly increased ERK-2 phosphorylation, an increase which was reduced by U73122 or PI-PLCγ2 siRNA. We conclude that TDCA-induced increase in NOX5-S expression and cell proliferation may depend on sequential activation of PI-PLCγ2 and ERK-2 MAP kinase in EA cells. It is possible that bile acid reflux present in patients with Barrett’s esophagus may increase ROS production and cell proliferation via activation of PI-PLCγ2, ERK-2 MAP kinase and NADPH oxidase NOX5-S, thereby contributing to the development of EA. PMID:20086178

  9. Vitamin D Receptor Polymorphisms Are Associated with Reduced Esophageal Vitamin D Receptor Expression and Reduced Esophageal Adenocarcinoma Risk

    PubMed Central

    Janmaat, Vincent T; van de Winkel, Anouk; Peppelenbosch, Maikel P; Spaander, Manon C W; Uitterlinden, André G; Pourfarzad, Farzin; Tilanus, Hugo W; Rygiel, Agnieszka M; Moons, Leon M G; Arp, Pascal P; Krishnadath, Kausilia K; Kuipers, Ernst J; van der Laan, Luc J W

    2015-01-01

    Epidemiological studies indicate that vitamin D exerts a protective effect on the development of various solid cancers. However, concerns have been raised regarding the potential deleterious role of high vitamin D levels in the development of esophageal adenocarcinoma (EAC). This study investigated genetic variation in the vitamin D receptor (VDR) in relation to its expression and risk of Barrett esophagus (BE) and EAC. VDR gene regulation was investigated by immunohistochemistry, reverse transcriptase–polymerase chain reaction (RT-PCR) and gel shift assays. Fifteen haplotype tagging single-nucleotide polymorphisms (SNPs) of the VDR gene were analyzed in 858 patients with reflux esophagitis (RE), BE or EAC and 202 healthy controls. VDR mRNA expression was higher in BE compared with squamous epithelium. VDR protein was located in the nucleus in BE. An rs1989969T/rs2238135G haplotype was identified in the 5′ regulatory region of the VDR gene. It was associated with an approximately two-fold reduced risk of RE, BE and EAC. Analysis of a replication cohort was done for BE that confirmed this. The rs1989969T allele causes a GATA-1 transcription factor binding site to appear. The signaling of GATA-1, which is regarded as a negative transcriptional regulator, could explain the findings for rs1989969. The rs2238135G allele was associated with a significantly reduced VDR expression in BE; for the rs1989969T allele, a trend in reduced VDR expression was observed. We identified a VDR haplotype associated with reduced esophageal VDR expression and a reduced incidence of RE, BE and EAC. This VDR haplotype could be useful in identifying individuals who benefit most from vitamin D chemoprevention. PMID:25910066

  10. Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

    PubMed Central

    Patch, Ann-Marie; Bailey, Peter; Newell, Felicity; Holmes, Oliver; Fink, J. Lynn; Quinn, Michael C.J.; Tang, Yue Hang; Lampe, Guy; Quek, Kelly; Loffler, Kelly A.; Manning, Suzanne; Idrisoglu, Senel; Miller, David; Xu, Qinying; Waddell, Nick; Wilson, Peter J.; Bruxner, Timothy J.C.; Christ, Angelika N.; Harliwong, Ivon; Nourse, Craig; Nourbakhsh, Ehsan; Anderson, Matthew; Kazakoff, Stephen; Leonard, Conrad; Wood, Scott; Simpson, Peter T.; Reid, Lynne E.; Krause, Lutz; Hussey, Damian J.; Watson, David I.; Lord, Reginald V.; Nancarrow, Derek; Phillips, Wayne A.; Gotley, David; Smithers, B. Mark; Whiteman, David C.; Hayward, Nicholas K.; Campbell, Peter J.; Pearson, John V.; Grimmond, Sean M.; Barbour, Andrew P.

    2015-01-01

    Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n = 40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. These findings suggest that genomic catastrophes have a significant role in the malignant transformation of EAC. PMID:25351503

  11. The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk.

    PubMed

    Becker, Jessica; May, Andrea; Gerges, Christian; Anders, Mario; Schmidt, Claudia; Veits, Lothar; Noder, Tania; Mayershofer, Rupert; Kreuser, Nicole; Manner, Hendrik; Venerito, Marino; Hofer, Jan-Hinnerk; Lyros, Orestis; Ahlbrand, Constantin J; Arras, Michael; Hofer, Sebastian; Heinrichs, Sophie K M; Weise, Katharina; Hess, Timo; Böhmer, Anne C; Kosiol, Nils; Kiesslich, Ralf; Izbicki, Jakob R; Hölscher, Arnulf H; Bollschweiler, Elfriede; Malfertheiner, Peter; Lang, Hauke; Moehler, Markus; Lorenz, Dietmar; Ott, Katja; Schmidt, Thomas; Nöthen, Markus M; Hackelsberger, Andreas; Schumacher, Brigitte; Pech, Oliver; Vashist, Yogesh; Vieth, Michael; Weismüller, Josef; Knapp, Michael; Neuhaus, Horst; Rösch, Thomas; Ell, Christian; Gockel, Ines; Schumacher, Johannes

    2016-05-01

    Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence. PMID:26783083

  12. Obesity and Risk of Esophageal Adenocarcinoma and Barrett’s Esophagus: A Mendelian Randomization Study

    PubMed Central

    Shaheen, Nicholas J.; Gammon, Marilie D.; Bernstein, Leslie; Reid, Brian J.; Onstad, Lynn; Risch, Harvey A.; Liu, Geoffrey; Bird, Nigel C.; Wu, Anna H.; Corley, Douglas A.; Romero, Yvonne; Chanock, Stephen J.; Chow, Wong-Ho; Casson, Alan G.; Levine, David M.; Zhang, Rui; Ek, Weronica E.; MacGregor, Stuart; Ye, Weimin; Hardie, Laura J.; Vaughan, Thomas L.; Whiteman, David C.

    2014-01-01

    Background Data from observational studies suggest that body mass index (BMI) is causally related to esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE). However, the relationships may be affected by bias and confounding. Methods We used data from the Barrett’s and Esophageal Adenocarcinoma Genetic Susceptibility Study: 999 patients with EAC, 2061 patients with BE, and 2169 population controls. We applied the two-stage control function instrumental variable method of the Mendelian randomization approach to estimate the unbiased, unconfounded effect of BMI on risk of EAC and BE. This was performed using a genetic risk score, derived from 29 genetic variants shown to be associated with BMI, as an instrument for lifetime BMI. A higher score indicates propensity to obesity. All tests were two-sided. Results The genetic risk score was not associated with potential confounders, including gastroesophageal reflux symptoms and smoking. In the instrumental variable analyses (IV), EAC risk increased by 16% (IV-odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.01 to 1.33) and BE risk increased by 12% (IV-OR = 1.12, 95% CI = 1.00 to 1.25) per 1kg/m2 increase in BMI. BMI was statistically significantly associated with EAC and BE in conventional epidemiologic analyses. Conclusions People with a high genetic propensity to obesity have higher risks of esophageal metaplasia and neoplasia than people with low genetic propensity. These analyses provide the strongest evidence to date that obesity is independently associated with BE and EAC, and is not due to confounding or bias inherent in conventional epidemiologic analyses. PMID:25269698

  13. MicroRNA Signature Characterizes Primary Tumors That Metastasize in an Esophageal Adenocarcinoma Rat Model

    PubMed Central

    Zaidi, Ali H.; Saldin, Lindsey T.; Kelly, Lori A.; Bergal, Linda; Londono, Ricardo; Kosovec, Juliann E.; Komatsu, Yoshihiro; Kasi, Pashtoon M.; Shetty, Amit A.; Keane, Timothy J.; Thakkar, Shyam J.; Huleihel, Luai; Landreneau, Rodney J.; Badylak, Stephen F.; Jobe, Blair A.

    2015-01-01

    Objective To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). Background The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. Methods The modified Levrat’s surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. Results The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. Conclusion In vivo metastasis was confirmed in the modified Levrat’s model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized. PMID:25826212

  14. Esophageal Adenocarcinoma in Patients Younger than 40 Years: A Two-Decade Experience at a Public and Private Hospital.

    PubMed

    Boys, Joshua A; Oh, Daniel S; Lewis, Justin S; DeMeester, Steven R; Hagen, Jeffrey A

    2015-10-01

    Esophageal adenocarcinoma is typically observed in the older non-Hispanic white population. Changing demographics are altering the epidemiology of the disease. The aim of this study is to review the presentation and outcomes of esophageal adenocarcinoma patients <40 years old at our institution. A retrospective review was performed of patients diagnosed with esophageal adenocarcinoma between 1990 and 2013. Demographics, presentation, and outcomes were compared in those <40 years old and those ?40 years old. There were 772 total cases with 42 (5%) <40 years old consisting of 37 (88.1%) males, five females and median age of diagnosis of 35 (interquartile range: 31-38). The two most common ethnicities were White non-Hispanic/Latino in 19 (45.2%), Hispanic /Latino in 18 (42.9%). Compared with patients 40 years and older, the younger group had more Hispanic/Latinos than the older group (43% vs 17%, P < 0.001), more frequently presented with stage IV disease (50% vs 29%) and had a shorter median survival. In conclusion, younger patients tend to present at a much later stage than the older counterparts, which may be due to a delay in diagnosis as well as more aggressive biology. Esophageal adenocarcinoma seems to be increasing in the Hispanic/Latino population. PMID:26463292

  15. Intakes of dietary folate and other B vitamins are associated with risks of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.

    PubMed

    Sharp, Linda; Carsin, Anne-Elie; Cantwell, Marie M; Anderson, Lesley A; Murray, Liam J

    2013-12-01

    Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Efficient folate metabolism requires other B vitamins and is adversely affected by smoking and alcohol. Esophageal adenocarcinoma (EAC) may develop through a process involving inflammation [reflux esophagitis (RE)] leading to metaplasia [Barrett's esophagus (BE)] and carcinoma. Within a population-based, case-control study, we investigated associations between dietary folate and related factors and risks of EAC, BE, and RE. EAC and BE cases had histologically confirmed disease; RE cases had endoscopically visible inflammation. Controls, age-sex frequency matched to EAC cases, were selected through population and general practice registers. Participants underwent structured interviews and completed food-frequency questionnaires. Multivariate ORs and 95% CIs were computed using logistic regression. A total of 256 controls and 223 EAC, 220 BE, and 219 RE cases participated. EAC risk decreased with increasing folate intake (OR highest vs. lowest = 0.56; 95% CI: 0.31, 1.00; P-trend < 0.01). Similar trends were found for BE (P-trend < 0.01) and RE (P-trend = 0.01). Vitamin B-6 intake was significantly inversely related to risks of all 3 lesions. Riboflavin intake was inversely associated with RE. Vitamin B-12 intake was positively associated with EAC. For EAC, there was a borderline significant interaction between folate intake and smoking (P-interaction = 0.053); compared with nonsmokers with high (≥ median) folate intake, current smokers with low intakes (

  16. A model for predicting individuals' absolute risk of esophageal adenocarcinoma: Moving toward tailored screening and prevention.

    PubMed

    Xie, Shao-Hua; Lagergren, Jesper

    2016-06-15

    Esophageal adenocarcinoma (EAC) is characterized by rapidly increasing incidence and poor prognosis, stressing the need for preventive and early detection strategies. We used data from a nationwide population-based case-control study, which included 189 incident cases of EAC and 820 age- and sex-matched control participants, from 1995 through 1997 in Sweden. We developed risk prediction models based on unconditional logistic regression. Candidate predictors included established and readily identifiable risk factors for EAC. The performance of model was assessed by the area under receiver operating characteristic curve (AUC) with cross-validation. The final model could explain 94% of all case patients with EAC (94% population attributable risk) and included terms for gastro-esophageal reflux symptoms or use of antireflux medication, body mass index (BMI), tobacco smoking, duration of living with a partner, previous diagnoses of esophagitis and diaphragmatic hernia and previous surgery for esophagitis, diaphragmatic hernia or severe reflux or gastric or duodenal ulcer. The AUC was 0.84 (95% confidence interval [CI] 0.81-0.87) and slightly lower after cross-validation. A simpler model, based only on reflux symptoms or use of antireflux medication, BMI and tobacco smoking could explain 91% of the case patients with EAC and had an AUC of 0.82 (95% CI 0.78-0.85). These EAC prediction models showed good discriminative accuracy, but need to be validated in other populations. These models have the potential for future use in identifying individuals with high absolute risk of EAC in the population, who may be considered for endoscopic screening and targeted prevention. PMID:26756848

  17. Clinical Study of Time Optimizing of Endoscopic Photodynamic Therapy on Esophageal and/or Gastric Cardiac Cancer

    ClinicalTrials.gov

    2015-12-10

    Stage I Esophageal Adenocarcinoma; Stage II Esophageal Adenocarcinoma; Stage III Esophageal Adenocarcinoma; Stage I Esophageal Squamous Cell Carcinoma; Stage II Esophageal Squamous Cell Carcinoma; Stage III Esophageal Squamous Cell Carcinoma

  18. Detection of fluorescent organic nanoparticles by confocal laser endomicroscopy in a rat model of Barrett’s esophageal adenocarcinoma

    PubMed Central

    Dassie, Elisa; Arcidiacono, Diletta; Wasiak, Iga; Damiano, Nunzio; Dall’Olmo, Luigi; Giacometti, Cinzia; Facchin, Sonia; Cassaro, Mauro; Guido, Ennio; De Lazzari, Franca; Marin, Oriano; Ciach, Tomasz; Fery-Forgues, Suzanne; Alberti, Alfredo; Battaglia, Giorgio; Realdon, Stefano

    2015-01-01

    For many years, novel strategies for cancer detection and treatment using nanoparticles (NPs) have been developed. Esophageal adenocarcinoma is the sixth leading cause of cancer-related deaths in Western countries, and despite recent advances in early detection and treatment, its prognosis is still very poor. This study investigated the use of fluorescent organic NPs as potential diagnostic tool in an experimental in vivo model of Barrett’s esophageal adenocarcinoma. NPs were made of modified polysaccharides loaded with [4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran] (DCM), a well-known fluorescent dye. The NP periphery might or might not be decorated with ASYNYDA peptide that has an affinity for esophageal cancer cells. Non-operated and operated rats in which gastroesophageal reflux was surgically induced received both types of NPs (NP-DCM and NP-DCM-ASYNYDA) by intravenous route. Localization of mucosal NPs was assessed in vivo by confocal laser endomicroscopy, a technique which enables a “real time” and in situ visualization of the tissue at a cellular level. After injection of NP-DCM and NP-DCM-ASYNYDA, fluorescence was observed in rats affected by esophageal cancer, whereas no signal was observed in control non-operated rats, or in rats with simple esophagitis or Barrett’s esophagus mucosa. Fluorescence was observable in vivo 30 minutes after the administration of NPs. Interestingly, NP-DCM-ASYNYDA induced strong fluorescence intensity 24 hours after administration. These observations suggested that NPs could reach the tumor cells, likely by enhanced permeability and retention effect, and the peptide ASYNYDA gave them high specificity for esophageal cancer cells. Thus, the combination of NP platform and confocal laser endomicroscopy could play an important role for highlighting esophageal cancer conditions. This result supports the potential of this strategy as a targeted carrier for photoactive and bioactive molecules in esophageal cancer diagnosis and treatment. PMID:26586943

  19. Role of intracellular calcium and NADPH oxidase NOX5-S in acid-induced DNA damage in Barrett's cells and Barrett's esophageal adenocarcinoma cells

    PubMed Central

    Li, Dan

    2014-01-01

    Mechanisms whereby acid reflux may accelerate the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. Acid and reactive oxygen species (ROS) have been reported to cause DNA damage in Barrett's cells. We have previously shown that NADPH oxidase NOX5-S is responsible for acid-induced H2O2 production in Barrett's cells and in EA cells. In this study we examined the role of intracellular calcium and NADPH oxidase NOX5-S in acid-induced DNA damage in a Barrett's EA cell line FLO and a Barrett's cell line CP-A. We found that pulsed acid treatment significantly increased tail moment in FLO and CP-A cells and histone H2AX phosphorylation in FLO cells. In addition, acid treatment significantly increased intracellular Ca2+ in FLO cells, an increase that is blocked by Ca2+-free medium with EGTA and thapsigargin. Acid-induced increase in tail moment was significantly decreased by NADPH oxidase inhibitor diphenylene iodonium in FLO cells, and by blockade of intracellular Ca2+ increase or knockdown of NOX5-S with NOX5 small-interfering RNA (siRNA) in FLO and CP-A cells. Acid-induced increase in histone H2AX phosphorylation was significantly decreased by NOX5 siRNA in FLO cells. Conversely, overexpression of NOX5-S significantly increased tail moment and histone H2AX phosphorylation in FLO cells. We conclude that pulsed acid treatment causes DNA damage via increase of intracellular calcium and activation of NOX5-S. It is possible that in BE acid reflux increases intracellular calcium, activates NOX5-S, and increases ROS production, which causes DNA damage, thereby contributing to the progression from BE to EA. PMID:24699332

  20. Radiation induced esophageal adenocarcinoma in a woman previously treated for breast cancer and renal cell carcinoma

    PubMed Central

    2012-01-01

    Background Secondary radiation-induced cancers are rare but well-documented as long-term side effects of radiation in large populations of breast cancer survivors. Multiple neoplasms are rare. We report a case of esophageal adenocarcinoma in a patient treated previously for breast cancer and clear cell carcinoma of the kidney. Case presentation A 56 year-old non smoking woman, with no alcohol intake and no familial history of cancer; followed in the National Institute of Oncology of Rabat Morocco since 1999 for breast carcinoma, presented on consultation on January 2011 with dysphagia. Breast cancer was treated with modified radical mastectomy, 6 courses of chemotherapy based on CMF regimen and radiotherapy to breast, inner mammary chain and to pelvis as castration. Less than a year later, a renal right mass was discovered incidentally. Enlarged nephrectomy realized and showed renal cell carcinoma. A local and metastatic breast cancer recurrence occurred in 2007. Patient had 2 lines of chemotherapy and 2 lines of hormonotherapy with Letrozole and Tamoxifen assuring a stable disease. On January 2011, the patient presented dysphagia. Oesogastric endoscopy showed middle esophagus stenosing mass. Biopsy revealed adenocarcinoma. No evidence of metastasis was noticed on computed tomography and breast disease was controlled. Palliative brachytherapy to esophagus was delivered. Patient presented dysphagia due to progressive disease 4 months later. Jejunostomy was proposed but the patient refused any treatment. She died on July 2011. Conclusion We present here a multiple neoplasm in a patient with no known family history of cancers. Esophageal carcinoma is most likely induced by radiation. However the presence of a third malignancy suggests the presence of genetic disorders. PMID:22873795

  1. Risk of Esophageal Adenocarcinoma Decreases With Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization

    PubMed Central

    Thrift, Aaron P.; Risch, Harvey A.; Onstad, Lynn; Shaheen, Nicholas J.; Casson, Alan G.; Bernstein, Leslie; Corley, Douglas A.; Levine, David M.; Chow, Wong–Ho; Reid, Brian J.; Romero, Yvonne; Hardie, Laura J.; Liu, Geoffrey; Wu, Anna H.; Bird, Nigel C.; Gammon, Marilie D.; Ye, Weimin; Whiteman, David C.; Vaughan, Thomas L.

    2014-01-01

    BACKGROUND & AIMS Risks for some cancers increase with height. We investigated the relationship between height and risk of esophageal adenocarcinoma (EAC) and its precursor, Barrett’s esophagus (BE). METHODS We analyzed epidemiologic and genome-wide genomic data from individuals of European ancestry in the Barrett’s and Esophageal Adenocarcinoma Consortium, from 999 cases of EAC, 2061 cases of BE, and 2168 population controls. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height and risks of EAC and BE. We performed a Mendelian randomization analysis to estimate an unconfounded effect of height on EAC and BE using a genetic risk score derived from 243 genetic variants associated with height as an instrumental variable. RESULTS Height was associated inversely with EAC (per 10-cm increase in height: OR, 0.70; 95% CI, 0.62–0.79 for men and OR, 0.57; 95% CI 0.40–0.80 for women) and BE (per 10-cm increase in height: OR, 0.69; 95% CI, 0.62–0.77 for men and OR, 0.61; 95% CI, 0.48–0.77 for women). The risk estimates were consistent across strata of age, education level, smoking, gastroesophageal reflux symptoms, body mass index, and weight. Mendelian randomization analysis yielded results quantitatively similar to those from the conventional epidemiologic analysis. CONCLUSIONS Height is associated inversely with risks of EAC and BE. Results from the Mendelian randomization study showed that the inverse association observed did not result from confounding factors. Mechanistic studies of the effect of height on EAC and BE are warranted; height could have utility in clinical risk stratification. PMID:24530603

  2. Squamous esophageal carcinoma and mucinous adenocarcinoma of the colon - an unusual association.

    PubMed

    Mirea, Cecil Sorin; Vasile, Manuela Ioana; Vîlcea, Ionică Daniel; Vasile, Ion; Moraru, Emil; Ciorbagiu, Mihai Călin; Sfeclan, Maria Cristina; Marin, Cătălina; Obleagă, Vasile Cosmin; Gheonea, Ioana Andreea; Vîlcea, Alina Maria

    2016-01-01

    The existence of a simultaneous cancer of the esophagus and colon is a rare situation that recognizes an increased incidence in recent years in the world, probably as a result of the improved measures of diagnosis and treatment, as well as the development of screening programs. The aim of this work is to present a case of synchronous esophageal squamous carcinoma with mucinous adenocarcinoma of the hepatic angle of the colon. The patient was hospitalized to our Surgical Clinic with the thoracic squamous esophageal carcinoma diagnosis. On admission, symptoms were dominated by overall dysphagia, patient showing a weight loss of 10 kg for the last 30 days. Preoperative imaging tests did not revealed regional or distant metastatic disease. Preoperative colonoscopy was incomplete (only until the splenic angle of the left colon) due to the insufficient mechanical preparation. On laparotomy, a carcinoma of the hepatic angle of the colon, partially stenosing was discovered. An upper pole esogastrectomy with intrathoracic esogastrostomy and a right colectomy with ileotransversostomy were practiced, at the same operative session. Postoperative evolution was poor and the patient died on the ninth day from the surgery during an alcohol withdrawal crisis. PMID:27151719

  3. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma

    PubMed Central

    Hedner, Charlotta; Borg, David; Nodin, Björn; Karnevi, Emelie; Jirström, Karin; Eberhard, Jakob

    2016-01-01

    Background Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma. Methods Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology. Results and Discussion High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods. PMID:26844548

  4. Genome-wide methylation analysis shows similar patterns in Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Xu, Enping; Gu, Jian; Hawk, Ernest T; Wang, Kenneth K; Lai, Maode; Huang, Maosheng; Ajani, Jaffer; Wu, Xifeng

    2013-12-01

    Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma (EAC). To identify novel tumor suppressors involved in esophageal carcinogenesis and potential biomarkers for the malignant progression of BE, we performed a genome-wide methylation profiling of BE and EAC tissues. Using Illumina's Infinium HumanMethylation27 BeadChip microarray, we examined the methylation status of 27 578 CpG sites in 94 normal esophageal (NE), 77 BE and 117 EAC tissue samples. The overall methylation of CpG sites within the CpG islands was higher, but outside of the CpG islands was lower in BE and EAC tissues than in NE tissues. Hierarchical clustering analysis showed an excellent separation of NE tissues from BE and EAC tissues; however, the clustering of BE and EAC tissues was less clear, suggesting that methylation occurs early during the progression of EAC. We confirmed many previously reported hypermethylated genes and identified a large number of novel hypermethylated genes in BE and EAC tissues, particularly genes encoding ADAM (A Disintegrin And Metalloproteinase) peptidase proteins, cadherins and protocadherins, and potassium voltage-gated channels. Pathway analysis showed that a number of channel and transporter activities were enriched for hypermethylated genes. We used pyrosequencing to validate selected candidate genes and found high correlations between the array and pyrosequencing data (rho > 0.8 for each validated gene). The differentially methylated genes and pathways may provide biological insights into the development and progression of BE and become potential biomarkers for the prediction and early detection of EAC. PMID:23996928

  5. Esophageal cancer

    MedlinePlus

    Cancer - esophagus ... Esophageal cancer is not common in the United States. It occurs most often in men over 50 years old. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. These two types ...

  6. Human epidermal growth factor receptor 2 overexpression and amplification in endoscopic biopsies and resection specimens in esophageal and junctional adenocarcinoma.

    PubMed

    van Hagen, P; Biermann, K; Boers, J E; Stoss, O; Sleddens, H F; van Lanschot, J J B; Dinjens, W N M; Rueschoff, J; Wijnhoven, B P L

    2015-01-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in a subset of esophageal adenocarcinomas. Frequently, biopsy material is used for evaluation of HER2 status. The aim of the study was to determine if HER2 expression in preoperative endoscopic biopsies is representative for the entire tumor. Preoperative endoscopic biopsies and matched resection specimens were collected from 75 patients who underwent esophagectomy for esophageal adenocarcinoma. Immunohistochemical staining (IHC) on HER2 and dual-color in situ hybridization (ISH) were performed. HER2 status was determined by following a clinical algorithm, first determining HER2 overexpression on immunohistochemistry and, when equivocal (2+), determining HER2 amplification on ISH. Seventy-one of 75 (95%) biopsies and 69/75 (92%) resection specimens could be analyzed due to technical failure. HER2 positivity was seen in 18/71 (25%) biopsies and in 15/69 (22%) resection specimens. Overall, HER2 status in the biopsy was concordant with HER2 status in the resection specimen in 94% of cases. Interobserver agreement on IHC scoring for all three observers was 83% in biopsies and 85% in resection specimens. HER2 positivity was detected in 22% of esophageal adenocarcinomas. Although interobserver agreement was moderate, HER2 status of a primary tumor can be reliably determined based on the endoscopically obtained pretreatment biopsy. PMID:24611982

  7. Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, HER2 overexpressing, esophageal adenocarcinoma

    SciTech Connect

    Safran, Howard . E-mail: hsafran@lifespan.org; Di Petrillo, Thomas; Akerman, Paul; Ng, Thomas; Evans, Devon; Steinhoff, Margaret; Benton, David; Purviance, John; Goldstein, Lisa; Tantravahi, Umadevi; Kennedy, Teresa R.N.

    2007-02-01

    Purpose: To determine the overall survival for patients with locally advanced, HER2 overexpressing, esophageal adenocarcinoma receiving trastuzumab, paclitaxel, cisplatin, and radiation on a Phase I-II study. Methods and Materials: Patients with adenocarcinoma of the esophagus without distant organ metastases and 2+/3+ HER2 overexpression by immunohistochemistry (IHC) were eligible. All patients received cisplatin 25 mg/m{sup 2} and paclitaxel 50 mg/m{sup 2} weekly for 6 weeks with radiation therapy (RT) 50.4 Gy. Patients received trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg. Results: Nineteen patients were entered: 7 (37%) had celiac adenopathy, and 7 (37%) had retroperitoneal, portal adenopathy, or scalene adenopathy. Fourteen of 19 patients (74%) had either 3+ HER2 expression by immunohistochemistry, or an increase in HER2 gene copy number by HER2 gene amplification or high polysomy by fluorescence in situ hybridization. The median survival of all patients was 24 months and the 2-year survival was 50%. Conclusions: Assessment of the effect of trastuzumab in the treatment of patients with esophageal adenocarcinoma overexpressing HER2 is limited by the small number of patients in this study. Overall survival, however, was similar to prior studies without an increase in toxicity. Evaluation of HER2 status should be performed in future trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HER family.

  8. HER 2 Expression in Gastric and Gastro-esophageal Junction (GEJ) Adenocarcinomas

    PubMed Central

    Rajagopal, Indu; Sahadev, R; Nagappa, Preethan Kamagere; Rajendra, Sowmya Goddanakoppal

    2015-01-01

    Introduction: Gastric cancer is one of the leading causes of cancer mortality in the world/India with majority being diagnosed at an advanced stage. Various chemotherapeutic regimens have modestly improved overall survival leading to quest for novel therapeutic agents. Overexpression of HER2 in many gastric cancers has lead to the advent of targeted therapy with anti HER2 antibody like Trastusumab which has improved the overall survival. Materials and Methods: Sixty cases of gastric adenocarcinomas (44 biopsies and 16 gastrectomies) over the past five years ( June 2009 to June 2014),were included in the study. Diagnosis was confirmed by review of slides and IHC with anti HER2 antibodies was performed using Dako Real Envision Detection system and scoring was done by Hoffmann et al., scoring system. Results: Of the 60 cases, majority were males (60%),with a mean age of 65.65 yrs. Tumours in antrum (76.7%) formed the major bulk. HER2 expression was observed in 26.7% of Tumours, predominantly in males (p=0.006) and intestinal type (p= 0.054). HER2 expression correlated with Tumour grade (moderately differentiated and well differentiated, p= 0.042). Tumours of gastro-esophageal junction (GEJ) showed HER2 expression in 45.5% as opposed to 22.4% in gastric location. Poorly differentiated and diffuse type of adenocarcinomas did not express HER2. Two of three Tumours from patients in the age group 31-40 y expressed HER2. Conclusion: Male gender, intestinal-type and moderately differentiated gastric cancers may be the ones that can be targeted for therapy using Herceptin. Though trastusumab is approved for advanced gastric and GEJ cancers, it’s role in adjuvant / neo-adjuvant setting in early stages needs to be evaluated with newer agents like Pertuzumab, Bevacizumab, especially in young patients. PMID:25954623

  9. Osteopontin (OPN/SPP1) isoforms collectively enhance tumor cell invasion and dissemination in esophageal adenocarcinoma

    PubMed Central

    Lin, Jules; Myers, Amy L.; Wang, Zhuwen; Nancarrow, Derek J.; Ferrer-Torres, Daysha; Handlogten, Amy; Leverenz, Kimmy; Bao, Julia; Thomas, Dafydd G.; Wang, Thomas D.; Orringer, Mark B.; Reddy, Rishindra M.; Chang, Andrew C.; Beer, David G.; Lin, Lin

    2015-01-01

    Esophageal adenocarcinoma (EAC) is often diagnosed at an advanced stage, thus understanding the molecular basis for EAC invasion and metastasis is critical. Here we report that SPP1/OPN was highly overexpressed in primary EACs and intracellularly localized to tumor cells. We further demonstrate that all known OPN isoforms (OPNa, b, c, 4 and 5) were frequently co-overexpressed in primary EACs. Distinct pro-invasion and dissemination phenotypes of isoform-specific OPNb and OPNc stable transfectants were observed. Expression of OPNb significantly enhanced cell migration and adhesion to laminin. In contrast, OPNc cells showed significantly decreased cell migration yet increased cell detachment. Enhanced invasion, both in vitro and in vivo, was observed for OPNb- but not OPNc-expressing cells. Inhibition of RGD integrins, one family of OPN receptors, attenuated OPNb cell migration, abrogated OPNb cell adhesion and significantly reduced OPNb cell clonogenic survival but did not affect OPNc phenotypes, indicating that OPNb but not OPNc acts through integrin-dependent signaling. Differential expression of vimentin, E-cadherin and β-catenin in OPN stable cells may account for the variation in cell adhesion and detachment between these isoforms. We conclude that while all OPN isoforms are frequently co-overexpressed in primary EACs, isoforms OPNb and OPNc enhance invasion and dissemination through collective yet distinct mechanisms. PMID:26068949

  10. Ion Mobility-Mass Spectrometry Analysis of Serum N-linked Glycans from Esophageal Adenocarcinoma Phenotypes

    PubMed Central

    Gaye, M. M.; Valentine, S. J.; Hu, Y.; Mirjankar, N.; Hammoud, Z. T.; Mechref, Y.; Lavine, B. K.; Clemmer, D. E.

    2012-01-01

    Three disease phenotypes, Barrett’s esophagus (BE), high-grade dysplasia (HGD), esophageal adenocarcinoma (EAC), and a set of normal control (NC) serum samples are examined using a combination of ion mobility spectrometry (IMS), mass spectrometry (MS) and principal component analysis (PCA) techniques. Samples from a total of 136 individuals were examined, including: 7 characterized as BE, 12 as HGD, 56 as EAC and 61 as NC. In typical datasets it was possible to assign ~20 to 30 glycan ions based on MS measurements. Ion mobility distributions for these ions show multiple features. In some cases, such as the [S1H5N4+3Na]3+ and [S1F1H5N4+3Na]3+ glycan ions, the ratio of intensities of high-mobility features to low-mobility features vary significantly for different groups. The degree to which such variations in mobility profiles can be used to distinguish phenotypes is evaluated for eleven N-linked glycan ions. An outlier analysis on each sample class followed by an unsupervised PCA using a genetic algorithm for pattern recognition reveals that EAC samples are separated from NC samples based on 46 features originating from the 11-glycan composite IMS distribution. PMID:23126309

  11. Geographic Distribution of Regional Metastatic Nodes Affects Outcome of Trimodality-Eligible Patients with Esophageal Adenocarcinoma

    PubMed Central

    Shiozaki, Hironori; Slack, Rebecca; Sudo, Kazuki; Elimova, Elena; Wadhwa, Roopma; Chen, Hsiang-Chun; Skinner, Heath D.; Komaki, Ritsuko; Lee, Jeffrey H.; Weston, Brian; Bhutani, Manoop S.; Blum, Mariela A.; Rogers, Jane E.; Maru, Dipen M.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2014-01-01

    Background Malignant nodes in patients with localized esophageal adenocarcinoma (L-EAC) portend a poor prognosis. We assessed the distribution of nodes to correlate with outcome of patients undergoing chemoradiation/surgery (trimodality). Methods We studied 209 L-EAC patients who had confirmed or suspicious nodes at baseline staging. All patients had trimodality therapy. Patients were grouped by nodal geography: above the diaphragm (AD), below the diaphragm (BD), or above and below the diaphragm (ABD). Survival estimates were calculated using the Kaplan-Meier method. The outcomes in subgroups were assessed by the log-rank test. Results Patients were primarily Caucasians (91%), men (93%), and had baseline stage III L-EAC (89%). The median follow-up was 2.8 years (range, 0.4 to 11.7 years). Of the 209 patients, 35% (n=73) had nodes AD, 20% (n=41) had nodes BD, and 45% (n=95) had nodes ABD. ABD patients had the 5-year overall survival rate of 33% compared to AD patients (55%) and BD (60%; P=0.02). Patients with higher histology grade were also at higher risk of relapse and had poor survival (P<0.01 for both). Conclusions L-EAC patients in the ABD group had worst outcome after trimodality compared to those in the AD or BD group. Novel strategies are needed for ABD patients. PMID:25765098

  12. Intractable Facial Pain and Numb Chin due to Metastatic Esophageal Adenocarcinoma

    PubMed Central

    Elahi, Foad; Luke, Whitney; Elahi, Fazel

    2014-01-01

    The etiologies of facial pain are innumerable, thus facial pain misdiagnosis and resultant mismanagement is common. Numb chin syndrome presents with hypoesthesia and/or anesthesia in the dermatomal distribution of the inferior alveolar or the mental nerve. In this case report, we will discuss a case of intractable facial pain in a 57-year-old male with a history of esophageal adenocarcinoma who was initially misdiagnosed and treated as trigeminal neuralgia. During clinical examination, the loss of sensation in the inferior alveolar nerve distribution was identified and led to the diagnosis of mandibular metastasis. The details of the clinical presentation will be discussed in the context of accurate identification and diagnosis. Focal radiation to the metastatic location along with sphenopalatine ganglion radiofrequency ablation and medication management provided significant pain relief. This case report provides additional information to the current medical knowledge and it enhances the clinical vigilance of the clinicians when they encounter similar cases. We concluded that patients with a history of neoplasms who present with atypical symptoms of facial pain should undergo further investigation with advanced imaging. Targeted treatment based on an accurate diagnosis is the foundation of pain management. PMID:25606033

  13. DNA Damage in CD133-Positive Cells in Barrett's Esophagus and Esophageal Adenocarcinoma

    PubMed Central

    Thanan, Raynoo; Ma, Ning; Hiraku, Yusuke; Iijima, Katsunori; Koike, Tomoyuki; Shimosegawa, Tooru

    2016-01-01

    Barrett's esophagus (BE) caused by gastroesophageal reflux is a major risk factor of Barrett's esophageal adenocarcinoma (BEA), an inflammation-related cancer. Chronic inflammation and following tissue damage may activate progenitor cells under reactive oxygen/nitrogen species-rich environment. We previously reported the formation of oxidative/nitrative stress-mediated mutagenic DNA lesions, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-nitroguanine, in columnar epithelial cells of BE tissues and cancer cells of BEA tissues. We investigated the mechanisms of BEA development in relation to oxidative/nitrative DNA damage and stem cell hypothesis. We examined 8-nitroguanine and 8-oxodG formation and the expression of stem cell marker (CD133) in biopsy specimens of patients with BE and BEA by immunohistochemical analysis in comparison with those of normal subjects. CD133 was detected at apical surface of columnar epithelial cells of BE and BEA tissues, and the cytoplasm and cell membrane of cancer cells in BEA tissues. DNA lesions and CD133 were colocalized in columnar epithelial cells and cancer cells. Their relative staining intensities in these tissues were significantly higher than those in normal subjects. Our results suggest that BE columnar epithelial cells with CD133 expression in apical surface undergo inflammation-mediated DNA damage, and mutated cells acquire the property of cancer stem cells with cytoplasmic CD133 expression. PMID:27069317

  14. Patient Preferences for the Chemoprevention of Esophageal Adenocarcinoma in Barretts Esophagus

    PubMed Central

    Hur, Chin; Broughton, Darcy E.; Ozanne, Elissa; Yachimski, Patrick; Nishioka, Norman S.; Gazelle, G. Scott

    2013-01-01

    OBJECTIVES Although evidence suggests that aspirin and celecoxib may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barretts esophagus (BE), these drugs can also cause harmful side effects. Our aim was to determine and characterize preferences for these two drugs in patients with BE. METHODS Preferences data were collected from recruited BE patients using a customized questionnaire, which incorporated standard risk communication techniques. Summary profiles outlined the benefits and harms of celecoxib and aspirin presented anonymously. Both drugs were portrayed as reducing the risk of EAC and increasing the risk of GI events. However, celecoxib increased the risk of myocardial infarction (MI) while aspirin reduced the risk. Factors influencing patient acceptance of each drug were analyzed. RESULTS One hundred of 109 (92%) subjects completed the study. Under base case conditions, 15% stated that they would take celecoxib and 76% aspirin (P < 0.0001). Patients identified the greater risk of MI as the primary reason for their unwillingness to take celecoxib and the lower risk of EAC for aspirin. Even in scenarios in which the benefits of celecoxib were improved and the harms reduced, a majority continued to find it unacceptable. CONCLUSIONS A majority of those surveyed stated that they would take aspirin but would not take celecoxib. Most patients are interested in EAC chemoprevention, but the amount of protection and the side effect profile of a drug determine its acceptability. These data can inform physicians regarding the tradeoffs patients are willing to consider for chemoprevention. PMID:18775019

  15. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.

    PubMed

    Dulak, Austin M; Stojanov, Petar; Peng, Shouyong; Lawrence, Michael S; Fox, Cameron; Stewart, Chip; Bandla, Santhoshi; Imamura, Yu; Schumacher, Steven E; Shefler, Erica; McKenna, Aaron; Carter, Scott L; Cibulskis, Kristian; Sivachenko, Andrey; Saksena, Gordon; Voet, Douglas; Ramos, Alex H; Auclair, Daniel; Thompson, Kristin; Sougnez, Carrie; Onofrio, Robert C; Guiducci, Candace; Beroukhim, Rameen; Zhou, Zhongren; Lin, Lin; Lin, Jules; Reddy, Rishindra; Chang, Andrew; Landrenau, Rodney; Pennathur, Arjun; Ogino, Shuji; Luketich, James D; Golub, Todd R; Gabriel, Stacey B; Lander, Eric S; Beer, David G; Godfrey, Tony E; Getz, Gad; Bass, Adam J

    2013-05-01

    The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a 5-year survival rate of ~15%, the identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole-exome sequencing of 149 EAC tumor-normal pairs, 15 of which have also been subjected to whole-genome sequencing. We identify a mutational signature defined by a high prevalence of A>C transversions at AA dinucleotides. Statistical analysis of exome data identified 26 significantly mutated genes. Of these genes, five (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) have previously been implicated in EAC. The new significantly mutated genes include chromatin-modifying factors and candidate contributors SPG20, TLR4, ELMO1 and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 identifies increased cellular invasion. Therefore, we suggest the potential activation of the RAC1 pathway as a contributor to EAC tumorigenesis. PMID:23525077

  16. Pralatrexate and Oxaliplatin in Treating Patients With Unresectable or Metastatic Esophageal, Stomach, or Gastroesophageal Junction Cancer

    ClinicalTrials.gov

    2016-01-11

    Adenocarcinoma of the Gastroesophageal Junction; Esophageal Undifferentiated Carcinoma; Gastric Adenocarcinoma; Gastric Squamous Cell Carcinoma; Recurrent Esophageal Adenocarcinoma; Recurrent Esophageal Squamous Cell Carcinoma; Recurrent Gastric Carcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIB Esophageal Squamous Cell Carcinoma; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Adenocarcinoma; Stage IIIC Esophageal Squamous Cell Carcinoma; Stage IIIC Gastric Cancer; Stage IV Esophageal Adenocarcinoma; Stage IV Esophageal Squamous Cell Carcinoma; Stage IV Gastric Cancer; Undifferentiated Gastric Carcinoma

  17. The importance of delivery rate on odds ratios by cigarette smoking and alcohol consumption for esophageal adenocarcinoma and squamous cell carcinoma in the Barretts and Esophageal Adenocarcinoma Consortium

    PubMed Central

    Lubin, Jay H.; Cook, Michael B.; Pandeya, Nirmala; Vaughan, Thomas L.; Abnet, Christian C.; Giffen, Carol; Webb, Penelope M.; Murray, Liam J.; Casson, Alan G.; Risch, Harvey A.; Ye, Weimin; Kamangar, Farin; Bernstein, Leslie; Sharp, Linda; Nyrn, Olof; Gammon, Marilie D.; Corley, Douglas A.; Wu, Anna H.; Brown, Linda M.; Chow, Wong-Ho; Ward, Mary H.; Freedman, Neal D.; Whiteman, David C.

    2012-01-01

    Background Cigarette smoking is associated with esophageal adenocarcinoma (EAC), esophagogastric junctional adenocarcinoma (EGJA) and esophageal squamous cell carcinoma (ESCC), and alcohol consumption with ESCC. However, no analyses have examined how delivery rate modifies the strength of odds ratio (OR) trends with total exposure, i.e., the impact on the OR for a fixed total exposure of high exposure rate for short duration compared with low exposure rate for long duration. Methods The authors pooled data from 12 case-control studies from the Barretts Esophagus and Esophageal Adenocarcinoma Consortium (BEACON), including 1,242 (EAC), 1,263 (EGJA) and 954 (ESCC) cases and 7,053 controls, modeled joint ORs for cumulative exposure and exposure rate for cigarette smoking and alcohol consumption, and evaluated effect modification by sex, body mass index (BMI), age and self-reported acid reflux. Results For smoking, all sites exhibited inverse delivery rate effects, whereby ORs with pack-years increased, but trends weakened with increasing cigarettes/day. None of the examined factors modified associations, except for ESCC where younger ages at diagnosis enhanced smoking effects (P<0.01). For EAC and EGJA, ORs with drink-years exhibited inverse associations in <5 drinks/day consumers and no association in heavier consumers. For ESCC, ORs with drink-years increased, with trends strengthening with greater drinks/day. There was no significant effect modification, except for EAC and EGJA where acid reflux mitigated the inverse associations (P=0.02). For ESCC, younger ages at diagnosis enhanced drinking-related ORs (P<0.01). Conclusions Patterns of ORs by pack-years and drink-years, delivery rate effects and effect modifiers revealed common as well as distinct etiologic elements for these diseases. PMID:22504051

  18. Local synthesis of pepsin in Barrett’s esophagus and the role of pepsin in esophageal adenocarcinoma

    PubMed Central

    Samuels, Tina; Hoekzema, Craig; Gould, Jon; Goldblatt, Matthew; Frelich, Matthew; Bosler, Matthew; Lee, Sang-Hyuk; Johnston, Nikki

    2016-01-01

    Objective Despite widespread use of proton pump inhibitors (PPIs), the incidence of esophageal adenocarcinoma (EAC) continues to rise. PPIs reduce reflux acidity, but only transiently inactivate gastric enzymes. Nonacid reflux, specifically nonacid pepsin, contributes to carcinogenesis in the larynx. Given the carcinogenic potential of pepsin and inefficacy of PPIs to prevent EAC, the presence and effect of pepsin in the esophagus should be investigated. Methods Normal and Barrett’s biopsies from eight Barrett’s esophagus patients were collected for pepsin analysis via Western blot and RT-PCR. Human esophageal cells cultured from healthy patients were treated with pepsin (0.01-1mg/ml; 1-20hours), acid (pH4) +/− pepsin (5minutes); real-time RT-PCR, ELISA and cell migration were assayed. Results Pepsin was detected in all eight Barrett’s, and four of eight adjacent normal specimens. Pepsinogen mRNA was observed in two Barrett’s, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL1β expression and cell migration in vitro. Conclusions Pepsin is synthesized by metaplastic, Barrett’s esophageal mucosa. Nonacid pepsin increases metrics of tumorigenicity in esophageal epithelial cells in vitro. These findings implicate refluxed and locally synthesized pepsin in development and progression of EAC and, in part, explain the inefficacy of PPIs in prevention of EAC. PMID:26077392

  19. Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Ek, Weronica E; Lagergren, Katarina; Cook, Michael; Wu, Anna H; Abnet, Christian C; Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Risch, Harvey A; Shaheen, Nicholas J; Bird, Nigel C; Corley, Douglas A; Hardie, Laura J; Fitzgerald, Rebecca C; Gammon, Marilie D; Romero, Yvonne; Liu, Geoffrey; Ye, Weimin; Vaughan, Thomas L; MacGregor, Stuart; Whiteman, David C; Westberg, Lars; Lagergren, Jesper

    2016-03-01

    The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed. PMID:26414697

  20. Synchronous primary esophageal squamous cell carcinoma and gastric adenocarcinoma: analysis of 41 cases treated in a single institution.

    PubMed

    Li, Xuyan; Lin, Suiling; Zhang, Yuling; Wang, Hongbiao

    2015-01-01

    The present study investigated the treatment and survival outcomes of patients with synchronous primary esophageal squamous cell carcinoma and gastric adenocarcinoma. The medical records of 10,783 patients with primary esophageal squamous cancer treated at our institution between 1995 and 2012 were retrospectively reviewed. Overall survival (OS) rates were calculated using the Kaplan-Meier method. The incidence was 0.38% (41/10,783). Of these 41 patients, 26 underwent curative surgery, ten received palliative chemotherapy or radiotherapy, and five received no treatment. The median OS of the surgery, palliative-therapy, and treatment-free groups was 17.1, 9.0, and 3.8 months, respectively. The 1-, 3-, 5-, and 10-year OS rates for the surgery group were 77%, 45%, 33%, and 19%, respectively. No significant differences in median OS were observed between the surgery group and the historical cohort of isolated esophageal cancer (n = 186) (17.1 vs. 21.0 months, P = 0.061) or isolated gastric cancer (n = 51) (17.1 vs. 28.9 months, P = 0.875), or between the palliative-therapy group and its corresponding historical cohort (n = 30) (9.0 vs. 8.3 months, P = 0.862). The survival outcomes of patients with synchronous primary esophageal squamous and gastric cancers were not worse than those of patients with isolated esophageal cancer or isolated gastric cancer. PMID:26290280

  1. Esophagitis resulting from treatment with crizotinib for anaplastic lymphoma kinase rearrangement-positive lung adenocarcinoma: A case report

    PubMed Central

    TAKAKUWA, OSAMU; OGURI, TETSUYA; YOKOYAMA, MIDORI; HIJIKATA, HISATOSHI; UEMURA, TAKEHIRO; OHKUBO, HIROTSUGU; MAENO, KEN; NIIMI, AKIO

    2014-01-01

    Non-small-cell lung cancer (NSCLC) is the most commonly diagnosed type of cancer and is a leading cause of cancer-related mortality worldwide. Treatment is currently focused on individualization according to the molecular profile of the disease. Here we present the case of a 41-year-old patient who presented with multiple pulmonary nodules, a left pleural effusion and an ovarian tumor. Adenocarcinoma of the lung was diagnosed from pathological examination of the pleural effusion and the surgically resected ovarian tumor, and chemotherapy was initiated. Relapse was experienced following third-line chemotherapy with pemetrexed and anaplastic lymphoma kinase (ALK)-positive adenocarcinoma was diagnosed using a specimen from the resected ovarian tumor. Subsequently, crizotinib therapy was initiated. Eight days later the patient developed severe nausea and vomiting and esophagitis was diagnosed by gastrointestinal endoscopic examination. Following the interruption of crizotinib treatment by treatment with a proton pump inhibitor (PPI), crizotinib treatment was re-initiated and was effective for a minimum of 6 months. Clinicians should be aware that treatment with crizotinib may result in severe esophagitis. PMID:24649319

  2. Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma.

    PubMed

    Becker, Jessica; May, Andrea; Gerges, Christian; Anders, Mario; Veits, Lothar; Weise, Katharina; Czamara, Darina; Lyros, Orestis; Manner, Hendrik; Terheggen, Grischa; Venerito, Marino; Noder, Tania; Mayershofer, Rupert; Hofer, Jan-Hinnerk; Karch, Hans-Werner; Ahlbrand, Constantin J; Arras, Michael; Hofer, Sebastian; Mangold, Elisabeth; Heilmann-Heimbach, Stefanie; Heinrichs, Sophie K M; Hess, Timo; Kiesslich, Ralf; Izbicki, Jakob R; Hölscher, Arnulf H; Bollschweiler, Elfriede; Malfertheiner, Peter; Lang, Hauke; Moehler, Markus; Lorenz, Dietmar; Müller-Myhsok, Bertram; Ott, Katja; Schmidt, Thomas; Whiteman, David C; Vaughan, Thomas L; Nöthen, Markus M; Hackelsberger, Andreas; Schumacher, Brigitte; Pech, Oliver; Vashist, Yogesh; Vieth, Michael; Weismüller, Josef; Neuhaus, Horst; Rösch, Thomas; Ell, Christian; Gockel, Ines; Schumacher, Johannes

    2015-11-01

    The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett's esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett's esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P < 10(-4) in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P < 10(-5) ) although not genome-wide significantly associated with the BEACON GWAS. Therefore, both variants and corresponding genes represent promising candidates for future EAC association studies on independent samples. PMID:26383589

  3. Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma

    PubMed Central

    Becker, Jessica; May, Andrea; Gerges, Christian; Anders, Mario; Veits, Lothar; Weise, Katharina; Czamara, Darina; Lyros, Orestis; Manner, Hendrik; Terheggen, Grischa; Venerito, Marino; Noder, Tania; Mayershofer, Rupert; Hofer, Jan-Hinnerk; Karch, Hans-Werner; Ahlbrand, Constantin J; Arras, Michael; Hofer, Sebastian; Mangold, Elisabeth; Heilmann-Heimbach, Stefanie; Heinrichs, Sophie K M; Hess, Timo; Kiesslich, Ralf; Izbicki, Jakob R; Hölscher, Arnulf H; Bollschweiler, Elfriede; Malfertheiner, Peter; Lang, Hauke; Moehler, Markus; Lorenz, Dietmar; Müller-Myhsok, Bertram; Ott, Katja; Schmidt, Thomas; Whiteman, David C; Vaughan, Thomas L; Nöthen, Markus M; Hackelsberger, Andreas; Schumacher, Brigitte; Pech, Oliver; Vashist, Yogesh; Vieth, Michael; Weismüller, Josef; Neuhaus, Horst; Rösch, Thomas; Ell, Christian; Gockel, Ines; Schumacher, Johannes

    2015-01-01

    The Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome-wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barrett’s esophagus. They identified genome-wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barrett’s esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P <  10−4 in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P < 10−5) although not genome-wide significantly associated with the BEACON GWAS. Therefore, both variants and corresponding genes represent promising candidates for future EAC association studies on independent samples. PMID:26383589

  4. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma.

    PubMed

    Shah, Alok K; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M

    2015-11-01

    We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates were independently verified by lectin magnetic bead array-immunoblotting, confirming the validity of the relative quantitation approach. Thus, we have identified candidate biomarkers, which, following large-scale clinical evaluation, can be developed into diagnostic blood tests. A key feature of the pipeline is the potential for rapid translation of the candidate biomarkers to lectin-immunoassays. PMID:26404905

  5. Medications (NSAID, Statins, PPI) and the Risk of Esophageal Adenocarcinoma in Patients with Barretts Esophagus

    PubMed Central

    Nguyen, Dang M.; Richardson, Peter; El-Serag, Hashem B.

    2010-01-01

    Background & Aims Limited evidence suggests that proton pump inhibitors (PPI), non-steroidal anti inflammatory drugs (NSAID)/aspirin and statins may be associated with low risk of esophageal neoplasia. However, the possible effect these medications may have on the risk of esophageal adenocarcinoma (EAC) in patients with existing Barretts esophagus (BE) is unclear. Methods We conducted a nested case-control study in a cohort of patients with BE identified in the national Department of Veterans Affairs (VA) computerized databases. Cases with incident EAC were matched by incidence density sampling to controls with BE who remained without EAC at the date of the EAC diagnosis for the corresponding case. We identified prescriptions for PPI, NSAID/aspirin, and statins that were filled between BE diagnosis and EAC diagnosis. Incidence density ratios were calculated using conditional logistic regression models that adjusted for race, outpatient encounters, a disease comorbidity index, and socio-economic status. Results In a cohort of 11,823 patients with first time BE diagnosis, we examined 116 EAC cases and 696 matched controls. Most cases and controls had at least one filled PPI prescription (95% vs. 94%, p=0.5). In this setting of almost universal PPI use, filled NSAID/aspirin prescriptions were associated with a reduced risk of EAC (adjusted incidence density ratio: 0.64; 95% CI, 0.420.97). Filled statin prescriptions were also associated with a reduction in EAC risk (0.55; 95% CI, 0.360.86), with a significant trend toward greater risk reduction with longer duration of statin use. However, the strong inverse associations with even short periods of use raise concerns of uncontrolled confounding. Conclusion This observational study indicates that in patients with Barretts esophagus using PPI, NSAID/aspirin or statin therapy might reduce the risk of developing esophageal adenocarcinoma. PMID:20188100

  6. Everolimus and Combination Chemotherapy in Treating Patients With Metastatic Stomach or Esophageal Cancer

    ClinicalTrials.gov

    2016-02-10

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  7. Esophageal atresia

    MedlinePlus

    ... infants with EA have another defect called tracheoesophageal fistula (TEF). This is an abnormal connection between the ... 2016:chap 42. Rothenberg SS. Esophageal atresia and tracheoesophageal fistula malformations. In: Holcomb GW, Murphy JP, Ostlie DJ, ...

  8. Deoxycholic acid induces the overexpression of intestinal mucin, MUC2, via NF-kB signaling pathway in human esophageal adenocarcinoma cells

    PubMed Central

    Wu, JianTao; Gong, Jun; Geng, Juan; Song, YinXue

    2008-01-01

    Background Mucin alterations are a common feature of esophageal neoplasia, and alterations in MUC2 mucin have been associated with tumor progression in the esophagus. Bile acids have been linked to esophageal adenocarcinoma and mucin secretion, but their effects on mucin gene expression in human esophageal adenocarcinoma cells is unknown. Methods Human esophageal adenocarcinoma cells were treated 18 hours with 50–300 μM deoxycholic acid, chenodeoxycholic acid, or taurocholic acid. MUC2 transcription was assayed using a MUC2 promoter reporter luciferase construct and MUC2 protein was assayed by Western blot analysis. Transcription Nuclear factor-κB activity was measured using a Nuclear factor-κB reporter construct and confirmed by Western blot analysis for Nuclear factor-κB p65. Results MUC2 transcription and MUC2 protein expression were increased four to five fold by bile acids in a time and dose-dependent manner with no effect on cell viability. Nuclear factor-κB activity was also increased. Treatment with the putative chemopreventive agent aspirin, which decreased Nuclear factor-κB activity, also decreased MUC2 transcription. Nuclear factor-κB p65 siRNA decreased MUC2 transcription, confirming the significance of Nuclear factor-κB in MUC2 induction by deoxycholic acid. Calphostin C, a specific inhibitor of protein kinase C (PKC), greatly decreased bile acid induced MUC2 transcription and Nuclear factor-κB activity, whereas inhibitors of MAP kinase had no effect. Conclusion Deoxycholic acid induced MUC2 overexpression in human esophageal adenocarcinoma cells by activation of Nuclear factor-κB transcription through a process involving PKC-dependent but not PKA, independent of activation of MAP kinase. PMID:19014523

  9. General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Steffen, Annika; Huerta, José-Maria; Weiderpass, Elisabete; Bueno-de-Mesquita, H B As; May, Anne M; Siersema, Peter D; Kaaks, Rudolf; Neamat-Allah, Jasmine; Pala, Valeria; Panico, Salvatore; Saieva, Calogero; Tumino, Rosario; Naccarati, Alessio; Dorronsoro, Miren; Sánchez-Cantalejo, Emilio; Ardanaz, Eva; Quirós, J Ramón; Ohlsson, Bodil; Johansson, Mattias; Wallner, Bengt; Overvad, Kim; Halkjaer, Jytte; Tjønneland, Anne; Fagherazzi, Guy; Racine, Antoine; Clavel-Chapelon, Françoise; Key, Tim J; Khaw, Kay-Tee; Wareham, Nick; Lagiou, Pagona; Bamia, Christina; Trichopoulou, Antonia; Ferrari, Pietro; Freisling, Heinz; Lu, Yunxia; Riboli, Elio; Cross, Amanda J; Gonzalez, Carlos A; Boeing, Heiner

    2015-08-01

    General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non-cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow-up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty-four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63-2.22 and HR = 3.76; 1.72-8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18-0.68, and HR=4.10; 1.94-8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09-3.37, and HR = 2.23; 1.28-3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation. PMID:25598323

  10. NADPH Oxidase NOX5-S and Nuclear Factor κB1 Mediate Acid-Induced Microsomal Prostaglandin E Synthase-1 Expression in Barrett’s Esophageal Adenocarcinoma Cells

    PubMed Central

    Zhou, Xiaoxu; Li, Dan; Resnick, Murray B.; Wands, Jack

    2013-01-01

    The mechanisms of progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not known. Cycloxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) has been shown to be important in esophageal tumorigenesis. We have shown that COX-2 mediates acid-induced PGE2 production. The prostaglandin E synthase (PGES) responsible for acid-induced PGE2 production in BE, however, is not known. We found that microsomal PGES1 (mPGES1), mPGES2, and cytosolic PGES (cPGES) were present in FLO EA cells. Pulsed acid treatment significantly increased mPGES1 mRNA and protein levels but had little or no effect on mPGES2 or cPGES mRNA. Knockdown of mPGES1 by mPGES1 small interfering RNA (siRNA) blocked acid-induced increase in PGE2 production and thymidine incorporation. Knockdown of NADPH oxidase, NOX5-S, a variant lacking calcium-binding domains, by NOX5 siRNA significantly inhibited acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Overexpression of NOX5-S significantly increased the luciferase activity in FLO cells transfected with a nuclear factor κB (NF-κB) in vivo activation reporter plasmid pNF-κB-Luc. Knockdown of NF-κB1 p50 by p50 siRNA significantly decreased acid-induced increase in mPGES1 expression, thymidine incorporation, and PGE2 production. Two novel NF-κB binding elements, GGAGTCTCCC and CGGGACACCC, were identified in the mPGES1 gene promoter. We conclude that mPGES1 mediates acid-induced increase in PGE2 production and cell proliferation. Acid-induced mPGES1 expression depends on activation of NOX5-S and NF-κB1 p50. Microsomal PGES1 may be a potential target to prevent or treat EA. PMID:23439561

  11. Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    Warren, Andrew; Cheetham, R. Keira; Northen, Helen; O’Donovan, Maria; Malhotra, Shalini; di Pietro, Massimiliano; Ivakhno, Sergii; He, Miao; Weaver, Jamie M.J.; Lynch, Andy G.; Kingsbury, Zoya; Ross, Mark; Humphray, Sean; Bentley, David; Fitzgerald, Rebecca C.

    2015-01-01

    The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett’s esophagus and EAC samples, together with one in-depth Barrett’s esophagus case-study sampled over time and space, we have provided new insights on the following aspects: i) Barrett’s esophagus is polyclonal and highly mutated even in the absence of dysplasia; ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett’s esophagus; and iii) despite differences in specific coding mutations the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett’s epithelium and a molecular Cytosponge™ technique overcomes sampling bias and has capacity to reflect the entire clonal architecture. PMID:26192915

  12. Elevated Tumor Expression of PAI-1 and SNAI2 in Obese Esophageal Adenocarcinoma Patients and Impact on Prognosis

    PubMed Central

    Allott, Emma H; Morine, Melissa J; Lysaght, Joanne; McGarrigle, Sarah A; Donohoe, Claire L; Reynolds, John V; Roche, Helen M; Pidgeon, Graham P

    2012-01-01

    OBJECTIVES: Obesity is linked to increased mortality from many cancer types, and esophageal adenocarcinoma (EAC) displays one of the strongest epidemiological associations. The aims of this study are to dissect molecular pathways linking obesity with EAC and to determine if obesity is linked to increased aggressiveness of this disease. METHODS: Affymetrix microarrays identified altered signaling pathways in an EAC cell line following coculture with visceral adipose tissue or isolated adipocytes from viscerally obese EAC patients (n=6). Differentially expressed genes were subsequently investigated in patient tumor biopsies by quantitative reverse transcriptase PCR and examined with respect to obesity status, tumor biology, and patient survival. RESULTS: Visceral adipose tissue induced expression of genes involved in epithelial mesenchymal transition (EMT), plasminogen activator inhibitor (PAI)-1, and transcription factor SNAI2, in an EAC cell line. In EAC patient tumor biopsies from obese patients, we noted elevated expression of these genes, together with reduced expression of epithelial marker E-cadherin. SNAI2 was associated with EAC prognosis. CONCLUSIONS: Expression of EMT genes, PAI-1 and SNAI2, was elevated in tumors of obese EAC patients, and SNAI2 was associated with poor survival. Genes deregulated in obesity and associated with prognosis may represent potential targets for treatment stratification of obese EAC patients. PMID:23238211

  13. Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

    PubMed

    Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

    2014-01-01

    Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers. PMID:24901722

  14. Polymorphism at the 3'-UTR of the thymidylate synthase gene: A potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation

    SciTech Connect

    Liao Zhongxing . E-mail: zliao@mdanderson.org; Liu Hongji; Swisher, Stephen G.; Wang Luo; Wu, Tsung-Teh; Correa, Arlene M.; Roth, Jack A.; Cox, James D.; Komaki, Ritsuko; Ajani, Jaffer A.; Wei Qingyi

    2006-03-01

    Purpose: To test the hypothesis that TS3'UTR polymorphisms predict outcomes in 146 Caucasian patients with esophageal adenocarcinoma treated with preoperative 5-fluorouracil-based chemoradiation. Methods and Materials: DNA was extracted from hematoxylin-and-eosin stained histologic slides of normal esophageal or gastric mucosa sections from paraffin blocks of esophagectomy specimens. Genotypes of the TS3'UTR polymorphism were determined by polymerase chain reaction for a 6-bp insertion. The genotype groups (0bp/0bp, 6bp/0bp, and 6bp/6bp) were compared for clinical features and overall survival, recurrence-free-survival, locoregional control (LRC), and distant metastasis control. Multivariable Cox regression analyses were performed to find independent predictors for the stated outcomes. Results: There was a trend of association between 6bp/6bp genotype and a decreased risk of local regional recurrence (hazards ratio = 0.211, 95% confidence interval = 0.041-1.095, p = 0.06) compared with other genotypes. There was a trend that patients with 6bp/6bp genotype had a higher 3-year probability of LRC compared with patients with the other two genotypes combined (p = 0.07); however, the difference was not statistically significant. Conclusions: The null hypotheses were not rejected in this study, probably owing to small sample size or the single gene examined. Prospective studies with adequate statistical power analyzing a family of genes involved in the 5-fluorouracil metabolism are needed to assess genetic determinants of treatment-related outcomes in esophageal adenocarcinoma.

  15. Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinoma

    PubMed Central

    2014-01-01

    Introduction The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract. Materials and methods Immunohistochemical PIGR expression was examined in a consecutive cohort of patients with surgically resected, radio-chemonaive adenocarcinoma of the esophagus, GE-junction and stomach (n = 173), including paired samples of benign-appearing squamous epithelium (n = 51), gastric mucosa (n = 114), Barrett’s esophagus (BE) or intestinal metaplasia (IM) (n = 57) and lymph node metastases (n = 75). Non-parametric tests were applied to explore associations between PIGR expression in primary tumours and clinicopathological characteristics. Classification and regression tree analysis was applied for selection of prognostic cut-off. The impact of PIGR expression on overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier analysis and hazard ratios (HR) calculated by adjusted and unadjusted Cox proportional hazards modelling. Results PIGR expression was significantly higher in intestinal metaplasia (BE or gastric IM) compared to normal tissues and cancer (p < 0.001). Reduced PIGR expression in primary tumours was significantly associated with more advanced tumour stage (p = 0.002) and inversely associated with involved margins (p = 0.034). PIGR expression did not differ between primary tumours and lymph node metastases. There was no significant difference in PIGR expression between tumours with and without a background of intestinal metaplasia. High PIGR expression was an independent predictor of a prolonged OS (HR = 0.60, 95% CI 0.36-0.99) and RFS (HR = 0.49, 95% CI 0.27-0.90) in patients with radically resected (R0) primary tumours and of an improved RFS (HR = 0.32, 95% CI 0.15-0.69) in curatively treated patients with R0 resection/distant metastasis-free disease. Conclusion High PIGR expression independently predicts a decreased risk of recurrence and an improved survival in patients with adenocarcinoma of the upper gastrointestinal tract. These findings are of potential clinical relevance and merit further validation. PMID:24694107

  16. PLCE1 mRNA and protein expression and survival of patients with esophageal squamous cell carcinoma and gastric adenocarcinoma

    PubMed Central

    Yang, Howard H; Su, Hua; Conway, Catherine M; Wang, Lemin; Wang, Chaoyu; Ding, Ti; Xu, Yi; Giffen, Carol; Abnet, Christian C; Goldstein, Alisa M; Hewitt, Stephen M; Taylor, Philip R

    2014-01-01

    Background Germline genetic variants in PLCE1 (10q23) have demonstrated consistent associations with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression in paired tumor-normal tissues, and their relationship with survival. Methods PLCE1 mRNA was profiled using three probes in the Affymetrix GeneChip U133 for paired tumor-normal tissues of ESCC (n=132), gastric cardia adenocarcinoma (GCA, n=62) and gastric noncardia adenocarcinoma (GNCA, n=72). We used immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in paired tumor-normal tissues of ESCC (n=303), and tumors of GCA (n=298) and GNCA (n=124). Results Compared with normal tissues, PLCE1 mRNA expression was significantly reduced in ESCC tumors (P=0.03, probe_205112_at), as well as in GCA and GNCA tumors (P<0.0001, each probe). Protein expression was non-significantly reduced in ESCC tumors (P=0.51). Increased tumor-normal mRNA fold change (probe_205112_at) was associated with longer survival in ESCC (9.6 months for highest vs lowest quartile; P-trend=0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; P-trend=0.04), but not for GNCA cases (P=0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was also associated with improved survival (8.1 months for highest quartile; P-trend=0.04). Conclusions Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression appears to be associated with cancer prognosis. Impact A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation. PMID:24867265

  17. C-Met Inhibitor AMG 337, Oxaliplatin, Leucovorin Calcium, and Fluorouracil in Treating Patients With Advanced Stomach or Esophageal Cancer

    ClinicalTrials.gov

    2015-01-16

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Gastrointestinal Cancer; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  18. Correlation of the location of superficial Barrett’s esophageal adenocarcinoma (s-BEA) with the direction of gastroesophageal reflux

    PubMed Central

    Omae, Masami; Fujisaki, Junko; Shimizu, Tomoki; Horiuchi, Yusuke; Ishiyama, Akiyoshi; Yoshio, Toshiyuki; Hirasawa, Toshiaki; Yamamoto, Yorimasa; Tsuchida, Tomohiro; Igarashi, Masahiro; Seto, Yasuyuki

    2016-01-01

    Background: Superficial Barrett’s esophageal adenocarcinoma (s-BEA) in Barrett’s esophagus frequently occurs in the right wall of the esophagus. Our aim was to examine the correlation between the location of s-BEA and the direction of acid and non-acid reflux in patients with Barrett’s esophagus. Patients and methods: We performed 24-h pH monitoring in 33 s-BEA patients using a pH catheter with eight sensors. One sensor was located at the 6 o’clock position in the lower esophagus and sensors 1 – 8 were arranged counterclockwise at the same level. The catheter was positioned at the same level as the s-BEA. We measured the maximal total duration of acid (MTD-A) and non-acid (MTD-NA) reflux. When the direction of MTD-A and MTD-NA coincided with the location of the s-BEA, the case was defined as coincidental and we calculated the rate of coincidence, and the probability of the rate of coincidence was estimated with 95 % confidence intervals (95 %CI). Results: Among the 33 cases of s-BEA examined, the rate of coincidence of both MTD-A and MTD-NA was 24/33 (72.7 %) (95 %CI 0.54 – 0.87). The rate of coincidence of either MTD-A or MTD-NA was 30/33 (90.9 %) (95 %CI 0.76 – 0.98). Conclusions: Our study revealed that the location of s-BEA mostly corresponds to the direction of MTD-A or MTD-NA. Accurate observation of the distribution of acid or non-acid reflux by pH monitoring would aid early detection of s-BEA by endoscopy.

  19. Cost-Effectiveness Analysis on Endoscopic Surveillance Among Western Patients With Barrett's Esophagus for Esophageal Adenocarcinoma Screening.

    PubMed

    Yang, Yu; Chen, Hai-Ning; Wang, Rui; Tang, Yun-Jing; Chen, Xin-Zu

    2015-09-01

    Incidence of esophageal adenocarcinoma (EAC) has risen rapidly over the past decades in Western countries. As a premalignant lesion, Barrett's esophagus (BE) is an established risk factor of EAC. This study estimated the impact of surveillance endoscopy for BE on population's survival upon EAC by a whole-population cost-effectiveness analysis among modeled Western population. Possibilities and survival payoffs were retrieved through literature searching based on PubMed database. Patients with BE were classified as adequate surveillance (AS), inadequate surveillance (IAS), and no surveillance groups. Direct cost of endoscopy per person-year was estimated from diagnosis of BE to before diagnosis of EAC in the whole-population model, whereas the payoff was 2-year disease-specific survival rate of EAC. AS for patients with BE had lower cost-effectiveness ratio (CER) than that of IAS group, as well as lower incremental cost-effectiveness ratio (6116 ∈/% vs 118,347 ∈/%). Prolonging the surveillance years could decrease the yearly cost in whole population and also relevant CERs, despite increased total cost. Increasing the proportion of participants in AS group could improve the survival benefit. The maximal payoff was up to 2-year mortality reduction of 2.7 per 100,000 persons by spending extra ∈ 1,658,913 per 100,000 person-years. A longer endoscopic surveillance among BE subpopulation plan can reduce yearly budget. Attempt to increase the proportion of AS participants can induce decline in population mortality of EAC, despite extra but acceptable expenditure. However, regarding optimal cost-effectiveness, further studies are still required to identify a high-risk subpopulation out of BE patients for endoscopic surveillance. PMID:26426603

  20. Dendritic Cells in Esophageal Adenocarcinoma: The Currently Available Information and Possibilities to use Dendritic Cells for Immunotherapeutic Approaches.

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-01-01

    Esophageal adenocarcinoma (EAC) is the second frequent cancer of the esophagus. Barrett's esophagus (BE) takes precedence over EAC. BE is a metaplastic change of the stratified squamous epithelium to the intestinal columnar epithelium due to the acidic gastrointestinal reflux. Further, the disease takes the hyperplastic stage followed by EAC. An initial immune response is an essential reaction of a body to an occurrence of alien/modified cells to be removed. It has been appreciated that an inflammatory reaction occurs in the early stages of EAC or even in BE. Dendritic cells (DCs) play a key role in a frontier of an immune response due to their advanced ability to recognize foreign antigens and mobilize naive T cells to effectors. However, in a cancer condition, tumor-delivered immunosuppression occurs in a variety of mechanisms that alter/switch the functionality of DCs from immune activating to immune suppressive cells. In this brief review, we consider tumor-induced paths of a capacity of tumor cells to down-regulate DCs, with a focus on EAC, and also discuss a possibility to use DCs for immunotherapeutic approaches. Indeed, DCs represent a promising tool for developing new immunotherapeutic approaches for cancer treatment including EAC. It has been reported to achieve effective DC-mediated immune responses by raising anti-tumor cytotoxic T cell responses against multiple cancer antigens through loading DCs with total tumor RNA. However, more studies should be performed in order to understand a precise role in tumor-induced mechanisms of DC suppression in BE/EAC. Likely, these mechanisms should involve general carcinogenic and EAC-specific pathways. PMID:26561054

  1. Iron intake and markers of iron status and risk of Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    O’Doherty, Mark G; Abnet, Christian C; Murray, Liam J; Woodside, Jayne V; Anderson, Lesley A; Brockman, John D; Cantwell, Marie M

    2012-01-01

    Objective To investigate the association between iron intake and iron status with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). Methods 220 BE patients, 224 EAC patients, and 256 frequency-matched controls completed a lifestyle and food frequency questionnaire, and provided serum and toenail samples between 2002 and 2005. Using multiple logistic regression, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated within quartiles of intake/status. Results Comparing the fourth to the first quartile, ferritin (OR 0.47; 95%CI: 0.23, 0.97) and transferrin saturation (OR 0.41; 95%CI: 0.20, 0.82) were negatively associated with BE; whilst total iron binding capacity was positively associated per 50 µg/dl increment (OR 1.47; 95%CI: 1.12, 1.92). Comparing the fourth to the first quartile, iron intake (OR 0.50; 95%CI: 0.25, 0.98), non-heme iron intake per 10 mg/day increment (OR 0.29; 95%CI: 0.08, 0.99), and toenail iron (OR 0.40; 95%CI: 0.17, 0.93) were negatively associated with EAC; whilst heme iron intake was positively associated (OR 3.11 95%CI: 1.46, 6.61). Principal conclusion In contrast to the hypothesis that increased iron intakes and higher iron stores are a risk factor for BE and EAC, this study suggests that higher iron intakes and stores may have a protective association with BE and EAC, with the exception of what was found for heme iron intake. PMID:20936528

  2. S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or gastro-esophageal junction adenocarcinoma patients: a pilot study

    PubMed Central

    Sun, Guoping; Lu, Huishan; Liu, Yunpeng; Zhong, Meizuo; Zhang, Helong; Yu, Shiying; Li, Wei; Hu, Xiaohua; Wang, Jiejun; Cheng, Ying; Zhou, Juntian; Guo, Zengqing; Guan, Zhongzhen; Xu, Ruihua

    2015-01-01

    The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China. PMID:26439700

  3. Surveillance in Patients With Barrett's Esophagus for Early Detection of Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Qiao, Yao; Hyder, Ayaz; Bae, Sandy J; Zarin, Wasifa; O'Neill, Tyler J; Marcon, Norman E; Stein, Lincoln; Thein, Hla-Hla

    2015-01-01

    Objectives: Although endoscopic surveillance of patients with Barrett's esophagus (BE) has been widely implemented for early detection of esophageal adenocarcinoma (EAC), its justification has been debated. This systematic review aimed to evaluate benefits, safety, and cost effectiveness of surveillance for patients with BE. Methods: MEDLINE, EMBASE, EconLit, Scopus, Cochrane, and CINAHL were searched for published human studies that examined screening practices, benefits, safety, and cost effectiveness of surveillance among patients with BE. Reviewers independently reviewed eligible full-text study articles and conducted data extraction and quality assessment, with disagreements resolved by consensus. Random effects meta-analyses were performed to assess the incidence of EAC, EAC/high-grade dysplasia (HGD), and annual stage-specific transition probabilities detected among BE patients under surveillance, and relative risk of mortality among EAC patients detected during surveillance compared with those not under surveillance. Results: A total of 51 studies with 11,028 subjects were eligible; the majority were of high quality based on the Newcastle–Ottawa quality scale. Among BE patients undergoing endoscopic surveillance, pooled EAC incidence per 1,000 person-years of surveillance follow-up was 5.5 (95% confidence interval (CI): 4.2–6.8) and pooled EAC/HGD incidence was 7.7 (95% CI: 5.7–9.7). Pooled relative mortality risk among surveillance-detected EAC patients compared with nonsurveillance-detected EAC patients was 0.386 (95% CI: 0.242–0.617). Pooled annual stage-specific transition probabilities from nondysplastic BE to low-grade dysplasia, high-grade dysplasia, and EAC were 0.019, 0.003, and 0.004, respectively. There was, however, insufficient scientific evidence on safety and cost effectiveness of surveillance for BE patients. Conclusions: Our findings confirmed a low incidence rate of EAC among BE patients undergoing surveillance and a reduction in mortality by 61% among those who received regular surveillance and developed EAC. Because of knowledge gaps, it is important to assess safety of surveillance and health-care resource use and costs to supplement existing evidence and inform a future policy decision for surveillance programs. PMID:26658838

  4. Pilot Trial of CRLX101 in Treatment of Patients With Advanced or Metastatic Stomach, Gastroesophageal, or Esophageal Cancer That Cannot be Removed by Surgery

    ClinicalTrials.gov

    2015-06-03

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  5. A Phase I/II Study of Oblimersen Plus Cisplatin and Fluorouracil in Gastric & Esophageal Junction Cancer

    ClinicalTrials.gov

    2015-06-10

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Esophageal Cancer; Recurrent Gastric Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer

  6. Principal component analysis of dietary and lifestyle patterns in relation to risk of subtypes of esophageal and gastric cancer

    PubMed Central

    Silvera, Stephanie A. Navarro; Mayne, Susan T; Risch, Harvey A.; Gammon, Marilie D; Vaughan, Thomas; Chow, Wong-Ho; Dubin, Joel A; Dubrow, Robert; Schoenberg, Janet; Stanford, Janet L; West, A. Brian; Rotterdam, Heidrun; Blot, William J

    2011-01-01

    Purpose To perform pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. Methods We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. Results PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing GERD/BMI score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. Conclusions PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, while fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC. PMID:21435900

  7. Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

    ClinicalTrials.gov

    2016-03-01

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer

  8. Intestinal Metaplasia is Present in Most if Not All Patients Who Have Undergone Endoscopic Mucosal Resection for Esophageal Adenocarcinoma.

    PubMed

    Smith, Jennifer; Garcia, Alfred; Zhang, Ruth; DeMeester, Steven; Vallone, John; Chandrasoma, Parakrama

    2016-04-01

    Barrett esophagus is presently defined in the United States by the presence of intestinal metaplasia in columnar-lined esophagus based on the premise that the risk for adenocarcinoma depends on the presence of intestinal metaplasia. Recently, arguments have been made that nonintestinalized cardiac epithelium is also at risk and should be included in the definition of Barrett esophagus, as it is in England and Japan. One of these arguments is that residual intestinal metaplasia is frequently absent around early adenocarcinomas removed by endoscopic mucosal resection (EMR). We reviewed 27 EMRs performed in 21 patients. Residual intestinal metaplasia was absent in 10/27 (37%) EMR specimens. An in-depth study of these 10 cases showed that 3 had intestinal metaplasia in a concurrent second EMR specimen, 4 had intestinal metaplasia in prior biopsy material available in our unit, and 2 had intestinal metaplasia in an esophagectomy that followed the EMR. The single patient in whom no intestinal metaplasia was found, neither in biopsies nor in EMR, and who did not undergo an esophagectomy had been under surveillance for Barrett esophagus for over 20 years. We conclude that the frequent absence of residual intestinal metaplasia around an adenocarcinoma in an EMR specimen is the result of sampling error. When evaluated in depth by looking at history, biopsies preceding the EMR, and esophagectomy following the EMR, all of these patients with adenocarcinoma had intestinal metaplasia in their columnar-lined esophagus. This indicates that intestinal metaplasia is a necessary precursor to adenocarcinoma of the esophagus. PMID:26813746

  9. Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma

    PubMed Central

    Krause, Lutz; Nones, Katia; Loffler, Kelly A.; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J.; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J.; Watson, David I.; Lord, Reginald V.; Phillips, Wayne A.; Gotley, David; Smithers, B.Mark; Whiteman, David C.; Hayward, Nicholas K.; Grimmond, Sean M.; Waddell, Nicola; Barbour, Andrew P.

    2016-01-01

    The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett’s esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. PMID:26905591

  10. Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation

    PubMed Central

    Kresty, Laura A.; Weh, Katherine M.; Zeyzus-Johns, Bree; Perez, Laura N.; Howell, Amy B.

    2015-01-01

    Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) were investigated utilizing acid-sensitive and acid-resistant human esophageal adenocarcinoma (EAC) cell lines and esophageal tumor xenografts in athymic NU/NU mice. C-PAC induced caspase-independent cell death mainly via autophagy and low levels of apoptosis in acid-sensitive JHAD1 and OE33 cells, but resulted in cellular necrosis in acid-resistant OE19 cells. Similarly, C-PAC induced necrosis in JHAD1 cells pushed to acid-resistance via repeated exposures to an acidified bile cocktail. C-PAC associated cell death involved PI3K/AKT/mTOR inactivation, pro-apoptotic protein induction (BAX, BAK1, deamidated BCL-xL, Cytochrome C, PARP), modulation of MAPKs (P-P38/P-JNK) and G2-M cell cycle arrest in vitro. Importantly, oral delivery of C-PAC significantly inhibited OE19 tumor xenograft growth via modulation of AKT/mTOR/MAPK signaling and induction of the autophagic form of LC3B supporting in vivo efficacy against EAC for the first time. C-PAC is a potent inducer of EAC cell death and is efficacious in vivo at non-toxic behaviorally achievable concentrations, holding promise for preventive or therapeutic interventions in cohorts at increased risk for EAC, a rapidly rising and extremely deadly malignancy. PMID:26378019

  11. Cranberry proanthocyanidins inhibit esophageal adenocarcinoma in vitro and in vivo through pleiotropic cell death induction and PI3K/AKT/mTOR inactivation.

    PubMed

    Kresty, Laura A; Weh, Katherine M; Zeyzus-Johns, Bree; Perez, Laura N; Howell, Amy B

    2015-10-20

    Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) were investigated utilizing acid-sensitive and acid-resistant human esophageal adenocarcinoma (EAC) cell lines and esophageal tumor xenografts in athymic NU/NU mice. C-PAC induced caspase-independent cell death mainly via autophagy and low levels of apoptosis in acid-sensitive JHAD1 and OE33 cells, but resulted in cellular necrosis in acid-resistant OE19 cells. Similarly, C-PAC induced necrosis in JHAD1 cells pushed to acid-resistance via repeated exposures to an acidified bile cocktail. C-PAC associated cell death involved PI3K/AKT/mTOR inactivation, pro-apoptotic protein induction (BAX, BAK1, deamidated BCL-xL, Cytochrome C, PARP), modulation of MAPKs (P-P38/P-JNK) and G2-M cell cycle arrest in vitro. Importantly, oral delivery of C-PAC significantly inhibited OE19 tumor xenograft growth via modulation of AKT/mTOR/MAPK signaling and induction of the autophagic form of LC3B supporting in vivo efficacy against EAC for the first time. C-PAC is a potent inducer of EAC cell death and is efficacious in vivo at non-toxic behaviorally achievable concentrations, holding promise for preventive or therapeutic interventions in cohorts at increased risk for EAC, a rapidly rising and extremely deadly malignancy. PMID:26378019

  12. Identification of the CIMP-like subtype and aberrant methylation of members of the chromosomal segregation and spindle assembly pathways in esophageal adenocarcinoma.

    PubMed

    Krause, Lutz; Nones, Katia; Loffler, Kelly A; Nancarrow, Derek; Oey, Harald; Tang, Yue Hang; Wayte, Nicola J; Patch, Ann Marie; Patel, Kalpana; Brosda, Sandra; Manning, Suzanne; Lampe, Guy; Clouston, Andrew; Thomas, Janine; Stoye, Jens; Hussey, Damian J; Watson, David I; Lord, Reginald V; Phillips, Wayne A; Gotley, David; Smithers, B Mark; Whiteman, David C; Hayward, Nicholas K; Grimmond, Sean M; Waddell, Nicola; Barbour, Andrew P

    2016-04-01

    The incidence of esophageal adenocarcinoma (EAC) has risen significantly over recent decades. Although survival has improved, cure rates remain poor, with <20% of patients surviving 5 years. This is the first study to explore methylome, transcriptome and ENCODE data to characterize the role of methylation in EAC. We investigate the genome-wide methylation profile of 250 samples including 125 EAC, 19 Barrett's esophagus (BE), 85 squamous esophagus and 21 normal stomach. Transcriptome data of 70 samples (48 EAC, 4 BE and 18 squamous esophagus) were used to identify changes in methylation associated with gene expression. BE and EAC showed similar methylation profiles, which differed from squamous tissue. Hypermethylated sites in EAC and BE were mainly located in CpG-rich promoters. A total of 18575 CpG sites associated with 5538 genes were differentially methylated, 63% of these genes showed significant correlation between methylation and mRNA expression levels. Pathways involved in tumorigenesis including cell adhesion, TGF and WNT signaling showed enrichment for genes aberrantly methylated. Genes involved in chromosomal segregation and spindle formation were aberrantly methylated. Given the recent evidence that chromothripsis may be a driver mechanism in EAC, the role of epigenetic perturbation of these pathways should be further investigated. The methylation profiles revealed two EAC subtypes, one associated with widespread CpG island hypermethylation overlapping H3K27me3 marks and binding sites of the Polycomb proteins. These subtypes were supported by an independent set of 89 esophageal cancer samples. The most hypermethylated tumors showed worse patient survival. PMID:26905591

  13. The Changing Face of Esophageal Cancer

    PubMed Central

    Melhado, Rachel E.; Alderson, Derek; Tucker, Olga

    2010-01-01

    The two main histological esophageal cancer types, adenocarcinoma and squamous cell carcinoma, differ in incidence, geographic distribution, ethnic pattern and etiology. This article focuses on epidemiology with particular reference to geographic and temporal variations in incidence, along with a review of the evidence supporting environmental and genetic factors involved in esophageal carcinogenesis. Squamous cell carcinoma of the esophagus remains predominantly a disease of the developing world. In contrast, esophageal adenocarcinoma is mainly a disease of western developed societies, associated with obesity and gastro-esophageal reflux disease. There has been a dramatic increase in the incidence of adenocarcinoma in developed countries in parallel with migration of both esophageal and gastric adenocarcinomas towards the gastro-esophageal junction. PMID:24281163

  14. Esophageal Cancer

    MedlinePlus

    ... Cancer Screening PDQ Screening Information for Patients Esophageal Cancer Screening More information Clinical Trials to Screen for Esophageal Cancer Statistics Esophageal cancer statistics based ...

  15. The relationship between pathologic nodal disease and residual tumor viability after induction chemotherapy in patients with locally advanced esophageal adenocarcinoma receiving a tri-modality regimen

    PubMed Central

    Rybicki, Lisa A.; Sohal, Davendra; Allende, Daniela S.; Videtic, Gregory M. M.; Rodriguez, Cristina P.; Stephans, Kevin L.; Murthy, Sudish C.; Raja, Siva; Raymond, Daniel; Ives, Denise I.; Bodmann, Joanna W.; Adelstein, David J.

    2016-01-01

    Background A complete pathologic response to induction chemo-radiotherapy (CRT) has been identified as a favorable prognostic factor for patients with loco-regionally advanced (LRA) adenocarcinoma (ACA) of the esophagus and gastro-esophageal junction (E/GEJ). Nodal involvement at the time of surgery has been found to be prognostically unfavorable. Less is known, however, about the prognostic import of less than complete pathologic regression and its relationship to residual nodal disease after induction chemotherapy. Methods Between February 2008 and January 2012, 60 evaluable patients with ACA of the E/GEJ enrolled in a phase II trial of induction chemotherapy, surgery, and post-operative CRT. Eligibility required a clinical stage of T3-T4 or N1 or M1a (AJCC 6th). Induction chemotherapy with epirubicin 50 mg/m2 d1, oxaliplatin 130 mg/m2 d1, and fluorouracil 200 mg/m2/day continuous infusion for 3 weeks, was given every 21 days for three courses and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy at 1.8-2.0 Gy/d and two courses of cisplatin (20 mg/m2/d) and fluorouracil (1,000 mg/m2/d) over 4 days during weeks 1 and 4 of radiotherapy. Residual viability (RV) was defined as the amount of remaining tumor in relation to acellular mucin pools and scarring. Results Of the 60 evaluable patients, 54 completed induction therapy and underwent curative intent surgery. The Kaplan-Meier projected 3-year overall survival (OS) for patients with pathologic N0 (n=20), N1 (n=12), N2 (n=13), and N3 (n=9) disease is 73%, 57%, 35%, and 0% respectively (P<0.001). The Kaplan-Meier projected 3-year OS of patients with low (0-25%, n=19), intermediate (26-75%, n=26), and high (>75%, n=9) residual tumor viability was 67%, 42%, and 17% respectively (P=0.004). On multivariable analysis (MVA), both the pN descriptor and RV were independently prognostic for OS. In patients with less nodal dissemination (N0/N1), RV was prognostic for OS [3-year OS 85% (0-25% viable) vs. 51% (>25% viable), P=0.028]. Outcomes were poor, however, for patients with advanced nodal disease (N2/N3) regardless of RV [3-year OS 20% (0-25% viable) vs. 21% (>25% viable), P=0.55]. Conclusions RV and the pN descriptor after induction chemotherapy are independent pathologic prognostic factors for OS in patients with LRA ACA of the E/GEJ. Patients with extensive nodal disease, however, have poor outcomes irrespective of residual tumor viability. PMID:27034786

  16. Upper esophageal and pharyngeal cancers

    PubMed Central

    Bock, Jonathan M.; Howell, Amy B.; Johnston, Nikki; Kresty, Laura A.; Lew, Daniel

    2014-01-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on laryngopharyngeal reflux as a risk factor for laryngeal cancer; the role of pepsin in laryngopharyngeal neoplasia; natural fruit and vegetable compounds for the prevention and treatment of pharyngeal and esophageal cancers; and evaluation of cranberry constituents as inhibitors of esophageal adenocarcinoma utilizing in vitro assay and in vivo models. PMID:25266014

  17. Restoring esophageal continuity following a failed colonic interposition for long-gap esophageal atresia

    PubMed Central

    Dionigi, Beatrice; Bairdain, Sigrid; Smithers, Charles Jason; Jennings, Russell W.; Hamilton, Thomas E.

    2015-01-01

    The Foker process is a method of esophageal lengthening through axial tension-induced growth, allowing for subsequent primary reconstruction of the esophagus in esophageal atresia (EA). In this unique case, the Foker process was used to grow the remaining esophageal segment long enough to attain esophageal continuity following failed colonic interpositions for long-gap esophageal atresia (LGEA). Initially developed for the treatment of LGEA in neonates, this case demonstrates that (i) an active esophageal lengthening response may still be present beyond the neonate time-period; and, (ii) the Foker process can be used to restore esophageal continuity following a failed colonic interposition if the lower esophageal segment is still present. PMID:25907539

  18. Improved body weight and performance status and reduced serum PGE2 levels after nutritional intervention with a specific medical food in newly diagnosed patients with esophageal cancer or adenocarcinoma of the gastro-esophageal junction

    PubMed Central

    Faber, Joyce; Uitdehaag, Madeleen J; Spaander, Manon; van Steenbergen-Langeveld, Sabine; Vos, Paul; Berkhout, Marloes; Lamers, Cor; Rümke, Hans; Tilanus, Hugo; Siersema, Peter; van Helvoort, Ardy; van der Gaast, Ate

    2015-01-01

    Background The majority of cancer patients loses weight and becomes malnourished during the course of their disease. Metabolic alterations and reduced immune competence lead to wasting and an increased risk of infectious complications. In the present study, the effect of a nutritionally complete medical food, which is high in protein and leucine and enriched with fish oil and specific oligosaccharides, was investigated on immune function, nutritional status, and inflammation in patients with esophageal cancer and compared with routine care. Methods In this exploratory double-blind study, 64 newly diagnosed esophageal cancer patients were randomized. All patients received dietary counselling and dietary advice. In the Active group, all patients received the specific medical food for 4 weeks before the start of anticancer therapy. In the routine care control arm, patients with <5% weight loss received a non-caloric placebo product, and patients with weight loss ≥5% received an iso-caloric control product to secure blinding of the study. The required study parameters of body weight and performance status were recorded at baseline and after 4 weeks of nutritional intervention, and patients were asked to complete quality of life questionnaires. In addition, blood samples were taken for the measurement of several immune, nutritional, and safety-parameters. Results No effect of the specific nutritional intervention could be detected on ex vivo stimulations of blood mononuclear cells. By contrast, body weight was significantly increased (P < 0.05) and ECOG performance status was improved after intervention with the specific medical food (P < 0.05). In addition, serum Prostaglandin E2 (PGE2) levels were significantly decreased in the specific medical food group and increased in the control group (P = 0.002). Conclusions Nutritional intervention with the specific medical food significantly increased body weight and improved performance status compared with routine care in newly diagnosed esophageal cancer patients. This effect was accompanied by significantly reduced serum PGE2 levels. PMID:26136410

  19. Esophageal malignancy: a growing concern.

    PubMed

    Chai, Jianyuan; Jamal, M Mazen

    2012-12-01

    Esophageal cancer is mainly found in Asia and east Africa and is one of the deadliest cancers in the world. However, it has not garnered much attention in the Western world due to its low incidence rate. An increasing amount of data indicate that esophageal cancer, particularly esophageal adenocarcinoma, has been rising by 6-fold annually and is now becoming the fastest growing cancer in the United States. This rise has been associated with the increase of the obese population, as abdominal fat puts extra pressure on the stomach and causes gastroesophageal reflux disease (GERD). Long standing GERD can induce esophagitis and metaplasia and, ultimately, leads to adenocarcinoma. Acid suppression has been the main strategy to treat GERD; however, it has not been proven to control esophageal malignancy effectively. In fact, its side effects have triggered multiple warnings from regulatory agencies. The high mortality and fast growth of esophageal cancer demand more vigorous efforts to look into its deeper mechanisms and come up with better therapeutic options. PMID:23236223

  20. Diet and lifestyle factors and risk of subtypes of esophageal and gastric cancer: classification tree analysis

    PubMed Central

    Navarro Silvera, Stephanie A; Mayne, Susan T; Gammon, Marilie D; Vaughan, Thomas L; Chow, Wong-Ho; Dubin, Joel A; Dubrow, Robert; Stanford, Janet L; West, A Brian; Rotterdam, Heidrun; Blot, William J; Risch, Harvey A

    2014-01-01

    Purpose Although risk factors for squamous cell carcinoma of the esophagus (SCC) and adenocarcinomas of the esophagus (EA), gastric cardia (GC) and other (non-cardia) gastric sites (OG) have been identified, little is known about interactions among risk factors. We sought to examine interactions of diet, other lifestyle, and medical factors with risks of subtypes of esophageal and gastric cancer. Methods We used classification tree analysis to analyze data from a population-based case-control study (1,095 cases, 687 controls) conducted in Connecticut, New Jersey, and western Washington State. Results Frequency of reported gastroesophageal reflux (GERD) symptoms was the most important risk stratification factor for EA, GC, and OG, with dietary factors (EA, OG), smoking (EA, GC), wine intake (GC, OG), age (OG), and income (OG) appearing to modify risk of these cancer sites. For SCC, smoking was the most important risk stratification factor, with GERD, income, race, non-citrus fruit, and energy intakes further modifying risk. Conclusion Various combinations of risk factors appear to interact to affect risk of each cancer subtype. Replication of these data-mining analyses are required before suggesting causal pathways; however, the classification tree results are useful in partitioning risk and mapping multi-level interactions among risk variables. PMID:24239095

  1. Complete and sustained objective response per RECIST to Irvalec (PM02734) in undifferentiated large cell esophageal adenocarcinoma: A case report and a review of the literature.

    PubMed

    Salazar, Ramón; Cuadra, Carmen; Gil-Martín, Marta; Vandermeeren, Andrea; Alfaro, Vicente; Coronado, Cinthya

    2012-05-01

    Undifferentiated large cell carcinoma is a rare entity in esophageal cancer and very few data are available in the literature on this uncommon histological subtype. We report a case of a 58-year-old Caucasian male previously treated with cisplatin/5-fluorouracil, docetaxel and carboplatin/plitidepsin who received treatment with a novel antitumor agent, Irvalec (PM02734), as fourth line. The patient received treatment from July 2006 to July 2009, a total of 49 cycles, at a dose of 2.4 mg/m(2) as a 24-hour infusion every 3 weeks. He did not present severe complications or unplanned or cumulative toxicities. Complete and durable response according to RECIST was reported. He was alive at the last follow-up on March 2012. PMID:22807904

  2. Complete and Sustained Objective Response per RECIST to Irvalec (PM02734) in Undifferentiated Large Cell Esophageal Adenocarcinoma: A Case Report and a Review of the Literature

    PubMed Central

    Salazar, Ramón; Cuadra, Carmen; Gil-Martín, Marta; Vandermeeren, Andrea; Alfaro, Vicente; Coronado, Cinthya

    2012-01-01

    Undifferentiated large cell carcinoma is a rare entity in esophageal cancer and very few data are available in the literature on this uncommon histological subtype. We report a case of a 58-year-old Caucasian male previously treated with cisplatin/5-fluorouracil, docetaxel and carboplatin/plitidepsin who received treatment with a novel antitumor agent, Irvalec (PM02734), as fourth line. The patient received treatment from July 2006 to July 2009, a total of 49 cycles, at a dose of 2.4 mg/m2 as a 24-hour infusion every 3 weeks. He did not present severe complications or unplanned or cumulative toxicities. Complete and durable response according to RECIST was reported. He was alive at the last follow-up on March 2012. PMID:22807904

  3. Intensity modulated radiation therapy with simultaneous integrated boost based dose escalation on neoadjuvant chemoradiation therapy for locally advanced distal esophageal adenocarcinoma

    PubMed Central

    Zeng, Ming; Aguila, Fernando N; Patel, Taral; Knapp, Mark; Zhu, Xue-Qiang; Chen, Xi-Lin; Price, Phillip D

    2016-01-01

    AIM: To evaluate impact of radiation therapy dose escalation through intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB). METHODS: We retrospectively reviewed the patients who underwent four-dimensional-based IMRT-SIB-based neoadjuvant chemoradiation protocol. During the concurrent chemoradiation therapy, radiation therapy was through IMRT-SIB delivered in 28 consecutive daily fractions with total radiation doses of 56 Gy to tumor and 5040 Gy dose-painted to clinical tumor volume, with a regimen at the discretion of the treating medical oncologist. This was followed by surgical tumor resection. We analyzed pathological completion response (pCR) rates its relationship with overall survival and event-free survival. RESULTS: Seventeen patients underwent dose escalation with the IMRT-SIB protocol between 2007 and 2014 and their records were available for analysis. Among the IMRT-SIB-treated patients, the toxicity appeared mild, the most common side effects were grade 1-3 esophagitis (46%) and pneumonitis (11.7%). There were no cardiac events. The Ro resection rate was 94% (n = 16), the pCR rate was 47% (n = 8), and the postoperative morbidity was zero. There was one mediastinal failure found, one patient had local failure at the anastomosis site, and the majority of failures were distant in the lung or bone. The 3-year disease-free survival and overall survival rates were 41% (n = 7) and 53% (n = 9), respectively. CONCLUSION: The dose escalation through IMRT-SIB in the chemoradiation regimen seems responsible for down-staging the distal esophageal with well-tolerated complications. PMID:27190587

  4. Esophagitis - infectious

    MedlinePlus

    Infectious esophagitis is rare. It often occurs in people whose immune systems are weakened. People who have ... people who are treated for an episode of infectious esophagitis need other, long-term medicines to suppress ...

  5. Esophageal Cancer

    MedlinePlus

    ... from your throat to your stomach. Early esophageal cancer usually does not cause symptoms. Later, you may ... You're at greater risk for getting esophageal cancer if you smoke, drink heavily, or have acid ...

  6. Eosinophilic esophagitis in patients with esophageal atresia and chronic dysphagia

    PubMed Central

    Kassabian, Sirvart; Baez-Socorro, Virginia; Sferra, Thomas; Garcia, Reinaldo

    2014-01-01

    Esophageal atresia (EA) is defined as a discontinuity of the lumen of the esophagus repaired soon after birth. Dysphagia is a common symptom in these patients, usually related to stricture, dysmotility or peptic esophagitis. We present 4 cases of patients with EA who complained of dysphagia and the diagnosis of Eosinophilic esophagitis (EoE) was made, ages ranging from 9 to 16 years. Although our patients were on acid suppression years after their EA repair, they presented with acute worsening of dysphagia. Esophogastroduodenoscopy and/or barium swallow did not show stricture and biopsies revealed elevated eosinophil counts consistent with EoE. Two of 4 patients improved symptomatically with the topical steroids. It is important to note that all our patients have asthma and 3 out of 4 have tested positive for food allergies. One of our patients developed recurrent anastomotic strictures that improved with the treatment of the EoE. A previous case report linked the recurrence of esophageal strictures in patients with EA repair with EoE. Once the EoE was treated the strictures resolved. On the other hand, based on our observation, EoE could be present in patients without recurrent anastomotic strictures. There appears to be a spectrum in the disease process. We are suggesting that EoE is a frequent concomitant problem in patients with history of congenital esophageal deformities, and for this reason any of these patients with refractory reflux symptoms or dysphagia (with or without anastomotic stricture) may benefit from an endoscopic evaluation with biopsies to rule out EoE. PMID:25548504

  7. Epidemiologic differences in esophageal cancer between Asian and Western populations.

    PubMed

    Zhang, Han-Ze; Jin, Guang-Fu; Shen, Hong-Bing

    2012-06-01

    Esophageal cancer is a common cancer worldwide and has a poor prognosis. The incidence of esophageal squamous cell cancer has been decreasing, whereas the incidence of esophageal adenocarcinoma has been increasing rapidly, particularly in Western men. Squamous cell cancer continues to be the major type of esophageal cancer in Asia, and the main risk factors include tobacco smoking, alcohol consumption, hot beverage drinking, and poor nutrition. In contrast, esophageal adenocarcinoma predominately affects the whites, and the risk factors include smoking, obesity, and gastroesophageal reflux disease. In addition, Asians and Caucasians may have different susceptibilities to esophageal cancer due to different heritage backgrounds. However, comparison studies between these two populations are limited and need to be addressed in the near future. Ethnic differences should be taken into account in preventive and clinical practices. PMID:22507220

  8. Evaluation of a four-protein serum biomarker panel – biglycan, annexin-A6, myeloperoxidase and protein S100-A9 (B-AMP©) – for detection of esophageal adenocarcinoma

    PubMed Central

    Zaidi, Ali H.; Gopalakrishnan, Vanathi; Kasi, Pashtoon M.; Zeng, Xuemei; Malhotra, Usha; Balasubramanian, Jeya; Visweswaran, Shyam; Sun, Mai; Flint, Melanie S.; Davison, Jon M.; Hood, Brian L.; Conrads, Thomas P.; Bergman, Jacques J.; Bigbee, William L.; Jobe, Blair A.

    2015-01-01

    Objective Esophageal adenocarcinoma (EAC) is associated with a dismal prognosis. The identification of cancer biomarkers advances the possibility for early detection and better monitoring of tumor progression and/or response to therapy. The current study presents results of the development of a serum based four-protein (biglycan, myeloperoxidase, annexin-A6, and protein S100-A9) biomarker-panel for EAC. Design A vertically integrated proteomics-based biomarker discovery approach was used to identify candidate serum biomarkers for detection of EAC. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis was performed on FFPE tissue samples that were collected from across the Barrett's esophagus (BE)-EAC disease spectrum. The MS-based spectral count data was used to guide the selection of candidate serum biomarkers. The serum ELISA data was validated in an independent cohort and used to develop a multi-parametric risk assessment model to predict the presence of disease. Results With a minimum threshold of 10 spectral counts, 351 proteins were identified as differentially abundant along the spectrum of BE, HGD and EAC (p < 0.05). Eleven proteins from this dataset were then tested using ELISAs in serum samples of which five proteins were significantly elevated in abundance in the EAC patients compared to normal controls, which mirrored trends across the disease spectrum present in the tissue data. Using serum data a Bayesian Rule Learning predictive model with four biomarkers was developed to accurately classify disease class; the cross-validation results for the merged dataset yielded accuracy of 87% and AUROC of 93 %. Conclusion Serum biomarkers hold significant promise for early non-invasive detection of EAC. PMID:25100294

  9. Esophageal development and epithelial homeostasis.

    PubMed

    Rosekrans, Sanne L; Baan, Bart; Muncan, Vanesa; van den Brink, Gijs R

    2015-08-15

    The esophagus is a relatively simple organ that evolved to transport food and liquids through the thoracic cavity. It is the only part of the gastrointestinal tract that lacks any metabolic, digestive, or absorptive function. The mucosa of the adult esophagus is covered by a multilayered squamous epithelium with a remarkable similarity to the epithelium of the skin despite the fact that these tissues originate from two different germ layers. Here we review the developmental pathways involved in the establishment of the esophagus and the way these pathways regulate gut-airway separation. We summarize current knowledge of the mechanisms that maintain homeostasis in esophageal epithelial renewal in the adult and the molecular mechanism of the development of Barrett's metaplasia, the precursor lesion to esophageal adenocarcinoma. Finally, we examine the ongoing debate on the hierarchy of esophageal epithelial precursor cells and on the presence or absence of a specific esophageal stem cell population. Together the recent insights into esophageal development and homeostasis suggest that the pathways that establish the esophagus during development also play a role in the maintenance of the adult epithelium. We are beginning to understand how reflux of gastric content and the resulting chronic inflammation can transform the squamous esophageal epithelium to columnar intestinal type metaplasia in Barrett's esophagus. PMID:26138464

  10. Herpetic esophagitis

    SciTech Connect

    Shortsleeve, M.J.; Gauvin, G.P.; Gardner, R.C.; Greenberg, M.S.

    1981-12-01

    Four patients with herpetic esophagitis were examined. In three of them, the presenting symptom was odynophagia. Early in the course of herpetic esophagitis, shallow round and oval ulcers were seen on barium esophagograms. Later, the ulcers filled with fibrinous exudate, forming nodular plaques that projected into the esophageal lumen. Although these findings are diagnostic of esophagitis, they are not specific for a herpes virus infection. The definitive diagnosis must be established by histologic examination, which demonstrates the cytopathic effect of the herpes virus infection within the squamous epithelium.

  11. Contractile profile of esophageal and gastric fundus strips in experimental doxorubicin-induced esophageal atresia.

    PubMed

    Capeto, F A; Lima, F J B; Okoba, W; Ramos, F L; Messias, T F A; Rigonatto, G A; Sbragia, L; Magalhes, P J C; Melo-Filho, A A

    2015-05-01

    Esophageal atresia (EA) is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO). Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA), and DOXO with EA (DOXO+EA). Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh). The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P<0.05). The maximum effect values (Emax) for DOXO+EA and DOXO-EA were significantly lower than control (P<0.05), but the half-maximal effective concentration (EC50) values were not significantly different when the three groups were compared (P>0.05). In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05). No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05). In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation. PMID:25760030

  12. Food group intake and risk of subtypes of esophageal and gastric cancer

    PubMed Central

    SA, Navarro Silvera; ST, Mayne; H, Risch; MD, Gammon; T, Vaughan; W-H, Chow; R, Dubrow; J, Schoenberg; JL, Stanford; AB, West; H, Rotterdam; WJ, Blot; JF, Fraumeni

    2010-01-01

    Incidence rates for adenocarcinomas of the esophagus and gastric cardia have been increasing rapidly, while rates for non-cardia gastric adenocarcinoma and esophageal squamous cell carcinoma have declined. We examined food group intake as a risk factor for subtypes of esophageal and gastric cancers in a multi-center, population-based case-control study in Connecticut, New Jersey, and western Washington state. Associations between food groups and risk were estimated using adjusted odds ratios (OR), based on increasing intake of one serving per day. Total vegetable intake was associated with decreased risk of esophageal adenocarcinoma (OR = 0.85, 95% CI = 0.75, 0.96). Conversely, total meat intake was associated with increased risk of esophageal adenocarcinoma (OR = 1.43, 95% CI = 1.11, 1.83), gastric cardia adenocarcinoma (OR = 1.37, 95% CI = 1.08, 1.73), and non-cardia gastric adenocarcinoma (OR = 1.39, 95% CI = 1.12, 1.71), with red meat most strongly associated with esophageal adenocarcinoma risk (OR = 2.49, 95% CI = 1.39, 4.46). Poultry was most strongly associated with gastric cardia adenocarcinoma (OR = 1.89, 95% CI = 1.15, 3.11) and non-cardia gastric adenocarcinoma (OR = 1.90, 95% CI = 1.19, 3.03). High-fat dairy was associated with increased risk of both esophageal and gastric cardia adenocarcinoma. Higher intake of meats, particularly red meats, and lower intake of vegetables were associated with an increased risk of esophageal adenocarcinoma, while higher intake of meats, particularly poultry, and high-fat dairy was associated with increased risk of gastric cardia adenocarcinoma. PMID:18537156

  13. Esophageal Cancer

    MedlinePlus

    ... lower part of the esophagus near the stomach. Squamous cell carcinoma - the most common type of esophageal cancer worldwide. ... use, and diseases such as achalasia can cause squamous cell carcinoma, while gastroesophageal reflux disease (GERD) can lead to ...

  14. Esophageal culture

    MedlinePlus

    ... for infection-causing germs in a sample of tissue from the esophagus. ... Culture - esophageal ... A sample of tissue from your esophagus is needed. The sample is ... or viruses. Other tests may be done to determine what medicine ...

  15. Esophageal perforation

    MedlinePlus

    ... or call 911 if: You have recently had surgery or a tube placed in the esophagus and you have pain, problems swallowing or breathing You have another reason to suspect that you may have esophageal perforation.

  16. Esophageal manometry

    MedlinePlus

    ... its ability to move food toward the stomach ( achalasia ) A weak LES, which causes heartburn (GERD) Abnormal contractions of the esophagus muscles that do not effectively move food to the stomach ( esophageal spasm )

  17. Management of refractory and complicated reflux esophagitis.

    PubMed

    Hirschowitz, B I

    1996-01-01

    Simple intermittent heartburn with minor or no esophagitis can be treated with simple measures including lifestyle changes and antacids as needed, or H2 receptor antagonists (H2RA), and has a good outcome. Problematic reflux includes resistance to therapy, stricture, Barrett's esophagus and aspiration. Severe reflux esophagitis, often resistant to H2RA therapy, requires more potent treatment with potent acid suppression using proton pump inhibitors, often indefinitely. When complicated by stricture, dilatations with potent acid suppression are needed. Barrett's esophagus is subject to esophagitis, which is no more difficult to treat than other cases of esophagitis. Reflux in Barrett's esophagus should be treated on its own merits without regard to the presence of Barrett's epithelium. Dysplasia leading to adenocarcinoma is a different problem, apparently not influenced by reduced exposure to acid. Indications for antireflux surgery are quite limited and should be carefully analyzed as a cost/risk/benefit problem. PMID:9165696

  18. Fatty acid synthase expression and esophageal cancer.

    PubMed

    Zhou, Yongli; Niu, Chunyan; Li, Yandong; Gao, Baohua; Zheng, Jianyun; Guo, Xiaoli; Ma, Weiguo

    2012-10-01

    Fatty acid synthase (FASN) overexpression has also been associated with a variety of human malignancies including tumor progression, aggressiveness, and metastasis. To investigate the role of FASN expression in esophageal cancer, we evaluated 60 cases of squamous cell carcinoma, 20 cases of adenocarcinoma, and 10 cases of normal esophageal tissues. We found that FASN was detected in 95 % human squamous cell carcinoma, and in 90 % human adenocarcinoma samples. However, all cases of normal esophageal epithelium did not express the protein of FASN. Further, to investigate the role of FASN in tumorigenesis and development, we analyze the growth and migration by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation and wound healing assay. We found that inhibition of FASN expression in TE13 cells by RNAi suppressed the growth of cells. Decreased FASN expression mitigated the migration of TE13 cells. These studies demonstrated the functional importance of FASN in esophageal tumorigenesis, and suggested that inhibiting FASN might be applied to treat esophageal cancer. PMID:22723001

  19. The imaging features of protruding esophageal lesions.

    PubMed

    Tomita, Hayato; Miyakawa, Kunihisa; Wada, Shinji; Okamoto, Satoko; Morimoto, Tsuyoshi; Kishimoto, Keiko; Nakajima, Yasuo

    2016-05-01

    Except for squamous cell carcinoma and adenocarcinoma, lesions that protrude into the esophagus are rare, and include benign and malignant tumors. The imaging findings of these lesions on esophagography, computed tomography (CT), and magnetic resonance imaging (MRI) are often non-specific. However, some of them reveal characteristic imaging findings. In addition, esophagography, CT, and MRI are useful to evaluate location, extent, invasion, vascularity, lymphadenopathy, and metastasis. Knowledge of the imaging features of protruding esophageal lesions helps to narrow the differential diagnosis. We describe the main features of esophageal protruding lesions. PMID:26968999

  20. Molecular Pathways: Pathogenesis and clinical implications of microbiome alteration in esophagitis and Barrett’s esophagus

    PubMed Central

    Yang, Liying; Francois, Fritz; Pei, Zhiheng

    2013-01-01

    Esophageal adenocarcinoma is preceded by the development of reflux-related intestinal metaplasia or Barrett’s esophagus which is a response to inflammation of the esophageal squamous mucosa, reflux esophagitis. Gastroesophageal reflux impairs the mucosal barrier in the distal esophagus, allowing chronic exposure of the squamous epithelium to the diverse microbial ecosystem or microbiome, and inducing chronic inflammation. The esophageal microbiome is altered in both esophagitis and Barrett's esophagus, characterized by a significant decrease in Gram-positive bacteria and an increase in Gram-negative bacteria in esophagitis and Barrett's esophagus. Lipopolysaccharides (LPS), a major structure of the outer membrane in Gram-negative bacteria, can up-regulate gene expression of proinflammatory cytokines via activation of the TLR4 and NF-kB pathway. The potential impact of LPS on reflux esophagitis may be through relaxation of the lower esophageal sphincter via iNOS and by delaying gastric emptying via COX-2. Chronic inflammation may be play a critical role in the progression from benign to malignant esophageal disease. Therefore analysis of the pathways leading to chronic inflammation in the esophagus may help to identify biomarkers in Barrett's esophagus patients for neoplastic progression and provide insight into molecular events suitable for therapeutic intervention in prevention of esophageal adenocarcinoma development in patients with reflux esophagitis and Barrett's esophagus. PMID:22344232

  1. Herpetic esophagitis (image)

    MedlinePlus

    Herpetic esophagitis is a herpes simplex infection causing inflammation and ulcers of the esophagus. Symptoms include difficulty swallowing and pain (dysphagia). Herpetic esophagitis can be effectively treated ...

  2. Eosinophilic esophagitis

    PubMed Central

    Merves, Jamie; Muir, Amanda; Chandramouleeswaran, Prasanna Modayur; Cianferoni, Antonella; Wang, Mei-Lun; Spergel, Jonathan M.

    2015-01-01

    Objective To review the understanding of the pathogenesis of eosinophilic esophagitis (EoE) and the role of the immune system in the disease process. Data Sources Peer-reviewed articles on EoE from PubMed searching for “Eosinophilic Esophagitis and fibrosis” in the period of 1995 to 2013. Study Selection Studies on the clinical and immunologic features, pathogenesis, and management of EoE. Results Recent work has revealed that thymic stromal lymphopoietin and basophil have an increased role in the pathogenesis of disease. Additional understanding on the role of fibrosis in EoE is emerging. Conclusion The incidence of EoE is increasing like most atopic disease. Similar to other allergic diseases, EoE is treated with topical steroids and/or allergen avoidance. PMID:24566295

  3. Prevention strategies for esophageal cancer: Perspectives of the East vs. West.

    PubMed

    Chung, Chen-Shuan; Lee, Yi-Chia; Wu, Ming-Shiang

    2015-12-01

    Esophageal cancer is the eighth most common cancer worldwide. Esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) are the two major phenotypes in Western and Eastern countries, respectively. Because of different pathways in carcinogenesis, the risk factors and effective steps for prevention of esophageal cancer are different between EAC and ESCC. The carcinogenesis of EAC is initiated by the acid exposure of the esophageal mucosa from stomach while that of the ESCC are related to the chronic irritation of carcinogens mainly by the alcohol, cigarette, betel quid, and hot beverage. To eliminate the burden of esophageal cancer on the global health, the effective strategy should be composed of the primary, secondary, and tertiary prevention. In this article, we perform a systematic review of the preventive strategies for esophageal cancer with special emphasis on the differences from the perspectives of Western and Eastern countries. PMID:26651249

  4. Androgens and esophageal cancer: What do we know?

    PubMed Central

    Sukocheva, Olga A; Li, Bin; Due, Steven L; Hussey, Damian J; Watson, David I

    2015-01-01

    Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer. PMID:26034350

  5. Adenocarcinoma

    Cancer.gov

    Compared to adenomas, adenocarcinomas show greater cytological atypia, increased frequency of mitoses, regional variation in growth pattern, more papillary structures, have size over 5 mm in diameter, show invasion of vessels, large airways or pleura, as well as lymphatic and hematogenous metastases.

  6. Etiology of esophageal atresia and tracheoesophageal fistula: "mind the gap".

    PubMed

    de Jong, Elisabeth M; Felix, Janine F; de Klein, Annelies; Tibboel, Dick

    2010-06-01

    Esophageal atresia and tracheoesophageal fistula (EA/TEF) are major congenital malformations affecting 1:3500 live births. Current research efforts are focused on understanding the etiology of these defects. We describe well-known animal models, human syndromes, and associations involving EA/TEF, indicating its etiologically heterogeneous nature. Recent advances in genotyping technology and in knowledge of human genetic variation will improve clinical counseling on etiologic factors. This review provides a clinical summary of environmental and genetic factors involved in EA/TEF. PMID:20425471

  7. Metastases of esophageal carcinoma to skeletal muscle: single center experience.

    PubMed

    Cincibuch, Jan; Mysliveček, Miroslav; Melichar, Bohuslav; Neoral, Cestmír; Metelková, Iva; Zezulová, Michaela; Procházková-Študentová, Hana; Flodr, Patrik; Zlevorová, Miloslava; Aujeský, René; Cwiertka, Karel

    2012-09-21

    Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma. In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases, muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma. In all cases, skeletal muscle metastases were the first manifestation of systemic disease. In three patients palliation was obtained with the combination of external beam radiation therapy, systemic chemotherapy or surgical resection. Skeletal muscle metastases are a rare complication of esophageal carcinoma. PMID:23002370

  8. Current endoscopic methods of radical therapy in early esophageal cancer

    PubMed Central

    Mocanu, A; Bârla, R; Hoara, P; Constantinoiu, S

    2015-01-01

    During the last three decades, there has been an increasing incidence of the esophageal cancer at the global level, approx. 400,000 new esophageal cancers being currently diagnosed annually. This is the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. If we refer to the countries of Western Europe and North America, we could see an increase in the esophageal adenocarcinoma in detriment of squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. Considering that the incidence of gastric cancer in Japan is very high, the endoscopic screenings performed inevitably led to an increased rate of early detection of esophageal cancer, reaching approximately 20% of all esophageal cancers detected. This has led to the possibility of developing therapeutic endoscopic techniques with radical visa that we will describe while presenting comparative data from literature. Currently, however, there are not enough data on the effectiveness of these types of therapies, compared to surgery, in order to be transformed into standard therapeutic endoscopic treatment for early esophageal cancer. However, the combined therapy, resection/ endoscopic ablation + chemoradiotherapy, appears as an alternative to be taken into account. Abbreviations EEC = esophageal early cancer, BE = Barrett’s esophagus, HGD = High-grade dysphagia, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE = Upper gastro endoscopy, PET-CT = Positron Emission Tomography, FNAB = Fine needle aspiration biopsy, EMR = Esophageal mucosal resection, ESD = Esophageal submucosal dissection, SCC = Squamous cellular cancer, PCT = Poli-chemotherapy, RT- Radio-therapy. PMID:25866570

  9. Robotic benign esophageal procedures.

    PubMed

    Hanna, Jennifer M; Onaitis, Mark W

    2014-05-01

    Robotic master-slave devices can assist surgeons to perform minimally invasive esophageal operations with approaches that have already been demonstrated using laparoscopy and thoracoscopy. Robotic-assisted surgery for benign esophageal disease is described for the treatment of achalasia, epiphrenic diverticula, refractory reflux, paraesophageal hernias, duplication cysts, and benign esophageal masses, such as leiomyomas. Indications and contraindications for robotic surgery in benign esophageal disease should closely approximate the indications for laparoscopic and thoracoscopic procedures. Given the early application of the technology and paucity of clinical evidence, there are currently no procedures for which robotic esophageal surgery is the clinically proven preferred approach. PMID:24780427

  10. Lymph Node Metastases in Esophageal Carcinoma: An Endoscopist's View.

    PubMed

    Cho, Jin Woong; Choi, Suck Chei; Jang, Jae Young; Shin, Sung Kwan; Choi, Kee Don; Lee, Jun Haeng; Kim, Sang Gyun; Sung, Jae Kyu; Jeon, Seong Woo; Choi, Il Ju; Kim, Gwang Ha; Jee, Sam Ryong; Lee, Wan Sik; Jung, Hwoon-Yong

    2014-11-01

    One of the most important prognostic factors in esophageal carcinoma is lymph node metastasis, and in particular, the number of affected lymph nodes, which influences long-term outcomes. The esophageal lymphatic system is connected longitudinally and transversally; thus, the pattern of lymph node metastases is very complex. Early esophageal cancer frequently exhibits skipped metastasis, and minimal surgery using sentinel node navigation cannot be performed. In Korea, most esophageal cancer cases are squamous cell carcinoma (SCC), although the incidence of adenocarcinoma has started to increase recently. Most previous reports have failed to differentiate between SCC and adenocarcinoma, despite the fact that the Union for International Cancer Control (7th edition) and American Joint Committee on Cancer staging systems both consider these separately because they differ in cause, biology, lymph node metastasis, and outcome. Endoscopic tumor resection is an effective and safe treatment for lesions with no associated lymph node metastasis. Esophageal mucosal cancer confined to the lamina propria is an absolute indication for endoscopic resection, and a lesion that has invaded the muscularis mucosae can be cured by local resection if invasion to the lymphatic system has not occurred. PMID:25505718

  11. [Esophageal stenting complications].

    PubMed

    Smoliar, A N; Radchenko, Iu A; Nefedova, G A; Abakumov, M M

    2014-01-01

    The aim of the study was to analyze esophageal stenting complications in case of cancer and benign diseases. It was investigated complications in 8 patients in terms from 7 days to 1 year after intervention. In 4 patients esophageal stenting was performed for constrictive esophageal cancer and compression with pulmonary cancer metastases into mediastinal lymphatic nodes. 2 patients had esophageal stenting for post-tracheostomy tracheo-esophageal fistula, 1 patient - for spontaneous esophageal rupture, 1 patient - for post-burn scar narrowing of esophagus and output part of the stomach. Severe patients' condition with tumor was determined by intensive esophageal bleeding in 2 cases, bilateral abscessed aspiration pneumonia, tumor bleeding, blood aspiration (1 case), posterior mediastinitis (1 case). Severe patients' condition with benign disease was associated with decompensated esophageal narrowing about proximal part of stent (1 case), increase of tracheo-esophageal fistula size complicated by aspiration pneumonia (1 case), stent migration into stomach with recurrence of esophago-mediastino-pleural fistula and pleural empyema (1 case), decompensated narrowing of esophagus and output part of the stomach (1 case). Patients with cancer died. And patients with benign diseases underwent multi-stage surgical treatment and recovered. Stenting is palliative method for patients with esophageal cancer. Patients after stenting should be under outpatient observation for early diagnosis of possible complications. Esophageal stenting in patients with benign diseases should be performed only by life-saving indications, in case of inability of other treatment and for the minimum necessary period. PMID:25589315

  12. Signaling pathways in the molecular pathogenesis of adenocarcinomas of the esophagus and gastroesophageal junction

    PubMed Central

    Clemons, Nicholas J; Phillips, Wayne A; Lord, Reginald V

    2013-01-01

    Esophageal adenocarcinoma develops in response to severe gastroesophageal reflux disease through the precursor lesion Barrett esophagus, in which the normal squamous epithelium is replaced by a columnar lining. The incidence of esophageal adenocarcinoma in the United States has increased by over 600% in the past 40 years and the overall survival rate remains less than 20% in the community. This review highlights some of the signaling pathways for which there is some evidence of a role in the development of esophageal adenocarcinoma. An increasingly detailed understanding of the biology of this cancer has emerged recently, revealing that in addition to the well-recognized alterations in single genes such as p53, p16, APC, and telomerase, there are interactions between the components of the reflux fluid, the homeobox gene Cdx2, and the Wnt, Notch, and Hedgehog signaling pathways. PMID:23792587

  13. High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death

    PubMed Central

    2014-01-01

    Background High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma. Material and methods Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett’s esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS). Results RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS). Conclusion High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation. PMID:24963396

  14. Mapping Local Cytosolic Enzymatic Activity in Human Esophageal Mucosa with Porous Silicon Nanoneedles.

    PubMed

    Chiappini, Ciro; Campagnolo, Paola; Almeida, Carina S; Abbassi-Ghadi, Nima; Chow, Lesley W; Hanna, George B; Stevens, Molly M

    2015-09-16

    Porous silicon nanoneedles can map Cathepsin B activity across normal and tumor human esophageal mucosa. Assembling a peptide-based Cathepsin B cleavable sensor over a large array of nano-needles allows the discrimination of cancer cells from healthy ones in mixed culture. The same sensor applied to tissue can map Cathepsin B activity with high resolution across the tumor margin area of esophageal adenocarcinoma. PMID:26197973

  15. Added Value of pH Multichannel Intraluminal Impedance in Adults Operated for Esophageal Atresia.

    PubMed

    Gatzinsky, Vladimir; Andersson, Olof; Eriksson, Anders; Jönsson, Linus; Abrahamsson, Kate; Sillén, Ulla

    2016-04-01

    Background Gastroesophageal reflux (GER) and dysphagia are common following repaired esophageal atresia (EA). The risk of esophagitis and Barrett esophagus is increased compared with the general population. As yet, the causes are not fully explained. Purpose The aim of this study was to investigate how GER, measured by pH multichannel intraluminal impedance (pH-MII), is correlated to the esophageal symptoms and histological findings. Methods Twenty-nine adult subjects operated for EA in Gothenburg from 1968 to 1983 were evaluated with pH-MII, manometry, and gastroscopy. Results pH-MII was performed in 15, manometry in 19, and gastroscopy in 24 subjects. Eleven subjects displayed pathological reflux parameters of any kind, mainly nonacid reflux (10/15). Dysphagia correlated to the number of weakly acidic reflux episodes. Lower esophageal sphincter (LES) incompetence, which correlated to a pathological number of acid reflux episodes (p = 0.012), was noted in 21/24 subjects, but the majority had a normal resting pressure. Esophagitis was present in 14/24, two of whom had Barrett esophagus. Histological changes correlated to the reflux index and the number of weakly acidic reflux episodes (p = 0.028 and 0.040) and tended to correlate to dysphagia (p = 0.052). Conclusion pH-MII adds further information when it comes to explaining what causes symptoms and esophageal histological changes in adults operated for EA. PMID:25643247

  16. Endoscopic resection of gastric and esophageal cancer

    PubMed Central

    Balmadrid, Bryan; Hwang, Joo Ha

    2015-01-01

    Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) techniques have reduced the need for surgery in early esophageal and gastric cancers and thus has lessened morbidity and mortality in these diseases. ESD is a relatively new technique in western countries and requires rigorous training to reproduce the proficiency of Asian countries, such as Korea and Japan, which have very high complete (en bloc) resection rates and low complication rates. EMR plays a valuable role in early esophageal cancers. ESD has shown better en bloc resection rates but it is easier to master and maintain proficiency in EMR; it also requires less procedural time. For early esophageal adenocarcinoma arising from Barrett’s, ESD and EMR techniques are usually combined with other ablative modalities, the most common being radiofrequency ablation because it has the largest dataset to prove its success. The EMR techniques have been used with some success in early gastric cancers but ESD is currently preferred for most of these lesions. ESD has the added advantage of resecting into the submucosa and thus allowing for endoscopic resection of more aggressive (deeper) early gastric cancer. PMID:26510452

  17. Adenocarcinoma of the cervical esophagus arising from ectopic gastric mucosa: report of two cases and review of the literature.

    PubMed

    Nomura, Kosuke; Iizuka, Toshiro; Inoshita, Naoko; Kuribayashi, Yasutaka; Toba, Takahito; Yamada, Akihiro; Yamashita, Satoshi; Furuhata, Tsukasa; Kikuchi, Daisuke; Matsui, Akira; Mitani, Toshifumi; Ogawa, Osamu; Hoteya, Shu; Ueno, Masaki; Udagawa, Harushi; Kaise, Mitsuru

    2015-12-01

    Esophageal adenocarcinoma arising from ectopic gastric mucosa (EGM) is extremely rare. We describe here two Japanese patients with adenocarcinoma of the cervical esophagus arising from EGM. Case 1 is a 62-year-old man who had slightly red EGM in the cervical esophagus on upper gastrointestinal endoscopy (UGE). Because the biopsy showed atypical glands that were suspicious for adenocarcinoma, endoscopic submucosal dissection was performed. Histopathological examination revealed that the lesion was a well-differentiated adenocarcinoma (pT1a MM). Lymphovascular invasion was absent, and the margins were free from carcinoma. Case 2 is a 57-year-old man who had an elevated lesion with a bleeding tendency in an area of EGM in the cervical esophagus on UGE. Adenocarcinoma was diagnosed in the biopsy. Because of the presence of enlarged lymph nodes (#106recL), preoperative chemoradiotherapy was performed to reduce the size of the adenocarcinoma and lymph nodes prior to resection of the cervical esophagus and reconstruction with free jejunal grafts. Histopathological examination revealed moderately differentiated adenocarcinoma (0-I, pT2N1M0, pStage II). In both cases, adenocarcinoma was surrounded by EGM, which led to the diagnosis of EGM-derived esophageal adenocarcinoma. Here, we report its immunohistochemical characteristics in the present cases and discuss the histogenesis. PMID:26476962

  18. Endoscopic palliation of advanced esophageal cancer

    PubMed Central

    Mocanu, A; Bârla, R; Hoara, P; Constantinoiu, S

    2015-01-01

    Esophageal cancer represents one of the most aggressive digestive tumors, with a survival rate at 5 years of only 10%. Globally, during the last three decades, there has been an increasing incidence of the esophageal cancer, approx. 400,000 new esophageal cancers being currently diagnosed annually. This represents the eighth leading cause of cancer incidence and the sixth leading cause of cancer death overall. Taking into account the population’s global aging and thus, the increase in the number of patients who will not bear surgery, PCT and radiation, or the fact that they do not want it especially because of deficiencies and associated pathology, the endoscopic ablative techniques with palliation purposes represent the alternative. If we refer to the Western Europe countries and North America, we notice an increase of esophageal adenocarcinoma rate versus squamous cancer. As for the Asian region, referring in particular to China and Japan, 9 out of 10 esophageal cancers are squamous cell carcinomas. For at least half of the patients with EC (esophageal cancer) there is no hope of healing because of the advanced regional malignant invasion (T3-4, N+, M+) with no chemo and radiotherapy response, poor preoperative patients’ conditions or systemic metastasis. The low life expectancy does not justify the risky medical procedures, the goal of the therapy consisting in the improvement of the quality of life by eliminating dysphagia (reestablishing oral feeding) which represents the most common complication of EC, the respiratory tract complication caused by eso-tracheal fistulas or by eliminating chest pain. To treat dysphagia, which is the main target of palliation, combined methods like endoscopic, chemo and radio-therapy, can be used, each one with indications, benefits and risks. Abbreviations: SEPS = self expanding plastic stent, SREMS = self expanding metal stent, EBRT = Endoscopic brachy radiotherapy, EUS = Ultra sound endoscopy, CT = Computer tomograph, UGE = Upper gastro endoscopy, PET-CT = Positron Emission Tomography, APC = argon plasma coagulation, PDT = photo dynamic therapy, PCT = Poli-chemotherapy, RT = Radio-therapy PMID:25866578

  19. Advances in targeted therapies and new promising targets in esophageal cancer.

    PubMed

    Belkhiri, Abbes; El-Rifai, Wael

    2015-01-30

    Esophageal cancer, comprising squamous carcinoma and adenocarcinoma, is a leading cause of cancer-related death in the world. Notably, the incidence of esophageal adenocarcinoma has increased at an alarming rate in the Western world. Unfortunately, the standard first-line chemo-radiotherapeutic approaches are toxic and of limited efficacy in the treatment of a significant number of cancer patients. The molecular analysis of cancer cells has uncovered key genetic and epigenetic alterations underlying the development and progression of tumors. These discoveries have paved the way for the emergence of targeted therapy approaches. This review will highlight recent progress in the development of targeted therapies in esophageal cancer. This will include a review of drugs targeting receptor tyrosine kinases and other kinases in esophageal cancer. Additional studies will be required to develop a rational integration of these targeted agents with respect to histologic types of esophageal cancer and the optimal selection of cancer patients who would most likely benefit from targeted therapy. Identification of AURKA and AXL as key molecular players in esophageal tumorigenesis and drug resistance strongly justifies the evaluation of the available drugs against these targets in clinical trials. PMID:25593196

  20. Methylation in esophageal carcinogenesis

    PubMed Central

    Wu, Da-Long; Sui, Feng-Ying; Jiang, Xiao-Ming; Jiang, Xiao-Hong

    2006-01-01

    Genetic abnormalities of proto-oncogenes and tumor suppressor genes have been demonstrated to be changes that are frequently involved in esophageal cancer pathogenesis. However, hypermethylation of CpG islands, an epigenetic event, is coming more and more into focus in carcinogenesis of the esophagus. Recent studies have proved that promoter hypermethylation of tumor suppressor genes is frequently observed in esophageal carcinomas and seems to play an important role in the pathogenesis of this tumor type. In this review, we will discuss current research on genes that are hypermethylated in human esophageal cancer and precancerous lesions of the esophagus. We will also discuss the potential use of hypermethylated genes as targets for detection, prognosis and treatment of esophageal cancer. PMID:17109513

  1. Esophageal stricture - benign

    MedlinePlus

    ... medicines) can keep a peptic stricture from returning. Surgery is rarely needed. If you have eosinophilic esophagitis, you may need to take medicines or make changes to your diet to reduce the inflammation. In some cases, dilation is done.

  2. Thoracoscopic Repair of Esophageal Atresia and Tracheoesophageal Fistula

    PubMed Central

    Holcomb, George W.; Rothenberg, Steven S.; Bax, Klaas M. A.; Martinez-Ferro, Marcelo; Albanese, Craig T.; Ostlie, Daniel J.; van Der Zee, David C.; Yeung, C K.

    2005-01-01

    Objectives: For the past 60 years, successful repair of esophageal atresia (EA) and distal tracheoesophageal fistula (TEF) has been performed via a thoracotomy. However, a number of reports have described adverse musculoskeletal sequelae following thoracotomy in infants and young children. Until now, only a few scattered case reports have detailed an individual surgeon's success with thoracoscopic repair of EA/TEF. This multi-institutional review represents the largest experience describing the results with this approach. Methods: A cohort of international pediatric surgeons from centers that perform advanced laparoscopic and thoracoscopic operations in infants and children retrospectively reviewed their data on primary thoracoscopic repair in 104 newborns with EA/TEF. Newborns with EA without a distal TEF or those with an isolated TEF without EA were excluded. Results: In these 104 patients, the mean age at operation was 1.2 days (1.1), the mean weight was 2.6 kg (0.5), the mean operative time was 129.9 minutes (55.5), the mean days of mechanical ventilation were 3.6 (5.8), and the mean days of total hospitalization were 18.1 (18.6). Twelve (11.5%) infants developed an early leak or stricture at the anastomosis and 33 (31.7%) required esophageal dilatation at least once. Five operations (4.8%) were converted to an open thoracotomy and one was staged due to a long gap between the 2 esophageal segments. Twenty-five newborns (24.0%) later required a laparoscopic fundoplication. A recurrent fistula between the esophagus and trachea developed in 2 infants (1.9%). A number of other operations were required in these patients, including imperforate anus repair in 10 patients (7 high, 3 low), aortopexy (7), laparoscopic duodenal atresia repair (4), and various major cardiac operations (5). Three patients died, one related to the EA/TEF on the 20th postoperative day. Conclusions: The thoracoscopic repair of EA/TEF represents a natural evolution in the operative correction of this complicated congenital anomaly and can be safely performed by experienced endoscopic surgeons. The results presented are comparable to previous reports of babies undergoing repair through a thoracotomy. Based on the associated musculoskeletal problems following thoracotomy, there will likely be long-term benefits for babies with this anomaly undergoing the thoracoscopic repair. PMID:16135928

  3. Current understanding of the functional roles of aberrantly expressed microRNAs in esophageal cancer

    PubMed Central

    Kestens, Christine; Siersema, Peter D; van Baal, Jantine WPM

    2016-01-01

    The incidence of esophageal cancer is rising, mostly because the increasing incidence of esophageal adenocarcinoma in Western countries. Despite improvements in diagnosis and treatment, the overall 5-year survival rates remain low. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the expression of target genes. Recently, disease specific miRNAs have been identified, which act as tumor suppressors or oncogenes. In this review, we will summarize the current knowledge about the function of aberrantly expressed miRNAs in esophageal cancer. We selected 5 miRNAs (miRNA-21, -143, -145, -196a and let-7) based on the available literature, and described their potential role in regulating pathways that are deregulated in esophageal cancer. Finally we will highlight the current achievements of using and targeting miRNAs. Because these miRNAs likely have important regulatory roles in cancer development, they open a therapeutic window for new treatment modalities. PMID:26755856

  4. Esophageal Atresia and Tracheoesophageal Fistula

    MedlinePlus

    ... Return to Web version Esophageal Atresia and Tracheoesophageal Fistula Overview What is esophageal atresia? In babies who ... gets into the stomach. What is a tracheoesophageal fistula? A fistula (say “fist-you-lah”) is a ...

  5. Esophageal pH monitoring

    MedlinePlus

    ... into the stomach. It is a test for gastroesophageal reflux disease ( GERD ). In infants, this test is also ... to: Barrett's esophagus Difficulty swallowing (dysphagia) Esophageal scarring Gastroesophageal reflux disease (GERD) Heartburn Reflux esophagitis You may need ...

  6. Mesothelin is a specific biomarker of invasive cancer in the Barrett-associated adenocarcinoma progression model Translational implications for diagnosis and therapy

    PubMed Central

    Alvarez, Hector; Rojas, Pamela Leal; Yong, Ken-Tye; Ding, Hong; Xu, Gaixia; Prasad, Paras N.; Wang, Jean; Canto, Marcia; Eshleman, James R.; Montgomery, Elizabeth A.; Maitra, Anirban

    2008-01-01

    Esophageal adenocarcinoma arises in the backdrop of Barrett metaplasia-dysplasia sequence, with the vast majority of patients presenting with late stage malignancy. Mesothelin, a GPI-anchored protein, is aberrantly overexpressed on the surface of many solid cancers. Mesothelin expression was assessed in esophageal tissue microarrays (TMAs) encompassing the entire histologic spectrum of Barrett-associated dysplasia and adenocarcinoma. Mesothelin expression was observed in 24/84 (29%) of invasive adenocarcinomas, and in 5/34 (15%) lymph node metastases. In contrast, normal squamous and cardia mucosa, as well as non-invasive Barrett lesions, failed to label with mesothelin. Mesothelin was expressed in the esophageal adenocarcinoma cell line JHU-EsoAd1, but not in primary human esophageal epithelial cells. Anti-mesothelin antibody conjugated CdSe/CDS/ZnS quantum rods (QRs) were synthesized as described (Young et al, NanoLetters, 2007), and confocal bio-imaging confirmed robust binding to JHU-EsoAd1 cells. Anti-mesothelin antibody conjugated nanoparticles can be useful for the diagnosis and therapy of mesothelin-overexpressing esophageal adenocarcinomas. PMID:18691948

  7. Patient-centered, comparative effectiveness of esophageal cancer screening: protocol for a comparative effectiveness research study to inform guidelines for evidence-based approach to screening and surveillance endoscopy

    PubMed Central

    2012-01-01

    Background The comparative effectiveness (CE) of endoscopic screening (versus no screening) for Barretts esophagus (BE) in patients with GERD symptoms, or among different endoscopic surveillance strategies in patients with BE, for the early detection of esophageal adenocarcinoma (EA) is unknown. Furthermore, it is unclear if patients or providers have or will adopt any of these strategies (screening only, screening and surveillance, vs. none), irrespective of their effectiveness. Endoscopic screening and surveillance is expensive and can be risky. Therefore, it is imperative to establish the CE and acceptability about the risks and outcomes related to these practices to better inform expert recommendations and provider-patient decisions. Methods/Results We propose a mixed methods study which will involve: (1) an analysis of secondary databases (VA and VA-Medicare linked datasets for 200409) to examine CE of endoscopic screening and surveillance in an observational study cohort (an estimated 680,000 patients with GERD; 25,00030,000 with BE; and 3,000 with EA); (2) a structured electronic medical record (EMR) review on a national sample of patients using VA EMRs to verify all EA cases, identify cancer stage, cancer-targeted therapy, and validate the screening and surveillance endoscopy; and (3) qualitative in depth interviews with patients and providers to elicit preferences, norms, and behaviors to explain clinical contexts of these findings and address gaps arising from the CE study. Conclusion This study will compare clinical strategies for detecting and monitoring BE, a pre-cancerous lesion. Additionally, by eliciting acceptability of these strategies for patients and providers, we will be able to propose effective and feasible strategies that are likely to be implemented in routine use. Findings will inform recommendations for clinical practice guidelines. Our innovative approach is consistent with the methodological standards of patient-centered outcomes research, and our findings will offer a significant contribution to the literature on cancer surveillance. Trial Registration Not applicable PMID:22929214

  8. Thoracoscopic repair of esophageal atresia with a distal fistula – lessons from the first 10 operations

    PubMed Central

    Zaborowska, Kamila; Rogowski, Błażej; Kalińska, Anita; Nosek, Marzena; Golonka, Anna; Lesiuk, Witold; Obel, Marcin

    2015-01-01

    Introduction Thoracoscopic esophageal atresia (EA) repair was first performed in 1999, but still the technique is treated as one of the most complex pediatric surgical procedures. Aim The study presents a single-center experience and learning curve of thoracoscopic repair of esophageal atresia and tracheo-esophageal (distal) fistula. Material and methods From 2012 to 2014, 10 consecutive patients with esophageal atresia and tracheo-esophageal fistula were treated thoracoscopically in our center. There were 8 girls and 2 boys. Mean gestational age was 36.5 weeks and mean weight was 2230 g. Four children had associated anomalies. The surgery was performed after stabilization of the patient between the first and fourth day after birth. Five patients required intubation before surgery for respiratory distress. Bronchoscopy was not performed before the operation. Results In 8 patients, the endoscopic approach was successfully used thoracoscopically, while in 2 patients conversion to an open thoracotomy was necessary. In all patients except 1, the anastomosis was patent, with no evidence of leak. One patient demonstrated a leak, which did not resolve spontaneously, necessitating surgical repair. In long-term follow-up, 1 patient required esophageal dilatation of the anastomosis. All patients are on full oral feeding. Conclusions The endoscopic approach is the method of choice for the treatment of esophageal atresia in our center because of excellent visualization and precise atraumatic preparation even in neonates below a weight of 2000 g. PMID:25960794

  9. Esophageal Cancer Screening

    MedlinePlus

    ... the type of cells that become malignant (cancerous): Squamous cell carcinoma : Cancer that begins in squamous cells , the thin, ... adenocarcinoma each year and fewer new cases of squamous cell carcinoma. Squamous cell carcinoma of the esophagus is found ...

  10. Adenocarcinoma of the esophagus: relationship to Barrett mucosa

    SciTech Connect

    Levine, M.S.; Caroline, D.; Thompson, J.J.; Kressel, H.Y.; Laufer, I.; Herlinger, H.

    1984-02-01

    Primary adenocarcinoma of the esophagus is thought to be a rare lesion. However, pathologic records at our institution from 1979 to 1982 show that adenocarcinoma accounted for 17 of 89 (19%) of all primary malignant tumors in the esophagus. All 17 cases arose in Barrett mucosa. In eight cases, there was surgically proved involvement of the gastric cardia or fundus. In six of these cases, there was evidence of esophageal dysplasia and/or carcinoma in situ adjacent to or remote from the proximal margin of the tumor. The pathologic findings therefore strongly suggest an esophageal origin of these lesions with subsequent spread into stomach. Clinical and radiographic findings at presentation were indistinguishable from those of squamous cell carcinoma. However, 10 patients had long-standing reflux symptoms, and Barrett esophagus had presumably been present for some time prior to the development of malignancy. Since adenocarcinoma evolves through a sequence of dysplasia and carcinoma in situ in pre-existing Barrett epithelium, the best hope for improving survival may be periodic endoscopic surveillance of asymptomatic individuals who have this condition.

  11. Using aptamers to elucidate esophageal cancer clinical samples

    PubMed Central

    Liu, Zhenxu; Lu, Yi; Pu, Ying; Liu, Jun; Liu, Bo; Yu, Bo; Chen, Ke; Fu, Ting; Yang, Chaoyong James; Liu, Huixia; Tan, Weihong

    2015-01-01

    The epithelial cell adhesion molecule (EpCAM) is closely correlated with the occurrence and development of various cancers of epithelial origin. This study tested, for the first time, the ability of EpCAM aptamer SYL3C to detect EpCAM expression in 170 cases of esophageal cancer (EC) and precancerous lesions, as well as 20 cases of EC series samples, using immunofluorescence imaging analysis. Corresponding antibodies were used as control. EpCAM overexpression was 98% in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EACA) and 100% in metastasis, but no EpCAM overexpression was detected in undifferentiated EC (UEC). Significant differences were noted among various stages of differentiation (p < 0.05) with the degree of differentiation inversely correlated with the expression of EpCAM. Overexpressed EpCAM was detected in severe dysplasia, but negative in mild to moderate dysplasia and benign esophageal lesions. In a competitive binding experiment, EpCAM aptamer generated a staining pattern similar to that of antibody, but the binding sites with EpCAM were different. Based on these results, it can be concluded that EpCAM is suitable for use as an EC biomarker, therapeutic target, and effective parameter for tumor transfer and prognosis evaluation by aptamer SYL3C staining. PMID:26687301

  12. Using aptamers to elucidate esophageal cancer clinical samples.

    PubMed

    Liu, Zhenxu; Lu, Yi; Pu, Ying; Liu, Jun; Liu, Bo; Yu, Bo; Chen, Ke; Fu, Ting; Yang, Chaoyong James; Liu, Huixia; Tan, Weihong

    2015-01-01

    The epithelial cell adhesion molecule (EpCAM) is closely correlated with the occurrence and development of various cancers of epithelial origin. This study tested, for the first time, the ability of EpCAM aptamer SYL3C to detect EpCAM expression in 170 cases of esophageal cancer (EC) and precancerous lesions, as well as 20 cases of EC series samples, using immunofluorescence imaging analysis. Corresponding antibodies were used as control. EpCAM overexpression was 98% in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EACA) and 100% in metastasis, but no EpCAM overexpression was detected in undifferentiated EC (UEC). Significant differences were noted among various stages of differentiation (p < 0.05) with the degree of differentiation inversely correlated with the expression of EpCAM. Overexpressed EpCAM was detected in severe dysplasia, but negative in mild to moderate dysplasia and benign esophageal lesions. In a competitive binding experiment, EpCAM aptamer generated a staining pattern similar to that of antibody, but the binding sites with EpCAM were different. Based on these results, it can be concluded that EpCAM is suitable for use as an EC biomarker, therapeutic target, and effective parameter for tumor transfer and prognosis evaluation by aptamer SYL3C staining. PMID:26687301

  13. Adenocarcinoma of the esophagus.

    PubMed Central

    Mahoney, J L; Condon, R E

    1987-01-01

    Adenocarcinoma involving the distal esophagus usually is far advanced when the patient is first seen. Adenocarcinoma differs from squamous carcinoma of the esophagus since it is relatively unresponsive to radiation therapy or chemotherapy. Adenocarcinoma of the esophagus resembles gastric cancer in its tendency to form a bulky and locally invasive tumor with early regional lymph node metastases. It differs from gastric cancer in its tendency to spread proximally in the esophagus and in the relatively infrequent early involvement of the liver by metastases. From 1979-1986, 37 patients had resection for adenocarcinoma involving the distal esophagus. Thirty-three patients were diagnosed with American Joint Committee for Cancer Stage III or IV adenocarcinoma at the time of operation. Transhiatal esophagectomy in continuity with a proximal gastrectomy was done in 27 patients. Reconstruction was accomplished by cervical esophagogastrostomy using pedicled distal stomach. There were three postoperative deaths (30-day mortality rate: 8%). Anastomotic leak occurred in nine patients and caused significant morbidity in four patients. Eleven patients required dilation of the cervical anastomosis after operation for up to 6 months. Mediastinal recurrence affected three patients treated by transhiatal esophagectomy. The survival rate (Kaplan-Meier) was 44% at 1 year and 31% at 2 years. Resection of adenocarcinoma of the esophagus can be accomplished in most patients with acceptable risks of morbidity and mortality. Resection restores ability to swallow saliva and to consume a normal diet, and is associated with an appreciable improvement in the quality of life. PMID:2437870

  14. Simultaneous Esophageal and Gastric Metastases from Lung Cancer.

    PubMed

    Park, Jae Yong; Hong, Seung Wook; Lee, Joo Young; Kim, Ji Hye; Kang, Jin Woo; Lee, Hyun Woo; Im, Jong Pil

    2015-07-01

    We report of a patient with metastatic adenocarcinoma of the esophagus and stomach from lung cancer. The patient was a 68-year-old man receiving radiotherapy and chemotherapy for stage IV lung cancer, without metastases to the gastrointestinal (GI) tract at the time of the initial diagnosis. During the treatment period, dysphagia and melena newly developed. Upper GI endoscopy revealed geographic erosion at the distal esophagus and multiple volcano-shaped ulcers on the stomach body. Endoscopic biopsy was performed for each lesion. To determine whether the lesions were primary esophageal and gastric cancer masses or metastases from the lung cancer, histopathological testing including immunohistochemical staining was performed, and metastasis from lung cancer was confirmed. The disease progressed despite chemotherapy, and the patient died 5 months after the diagnosis of lung cancer. This is a case report of metastatic adenocarcinoma in the esophagus and stomach, which are very rare sites of spread for lung cancer. PMID:26240809

  15. Simultaneous Esophageal and Gastric Metastases from Lung Cancer

    PubMed Central

    Park, Jae Yong; Hong, Seung Wook; Lee, Joo Young; Kim, Ji Hye; Kang, Jin Woo; Lee, Hyun Woo

    2015-01-01

    We report of a patient with metastatic adenocarcinoma of the esophagus and stomach from lung cancer. The patient was a 68-year-old man receiving radiotherapy and chemotherapy for stage IV lung cancer, without metastases to the gastrointestinal (GI) tract at the time of the initial diagnosis. During the treatment period, dysphagia and melena newly developed. Upper GI endoscopy revealed geographic erosion at the distal esophagus and multiple volcano-shaped ulcers on the stomach body. Endoscopic biopsy was performed for each lesion. To determine whether the lesions were primary esophageal and gastric cancer masses or metastases from the lung cancer, histopathological testing including immunohistochemical staining was performed, and metastasis from lung cancer was confirmed. The disease progressed despite chemotherapy, and the patient died 5 months after the diagnosis of lung cancer. This is a case report of metastatic adenocarcinoma in the esophagus and stomach, which are very rare sites of spread for lung cancer. PMID:26240809

  16. Clinical and etiological heterogeneity in patients with tracheo-esophageal malformations and associated anomalies.

    PubMed

    Brosens, Erwin; Ploeg, Mirjam; van Bever, Yolande; Koopmans, Anna E; IJsselstijn, Hanneke; Rottier, Robbert J; Wijnen, Rene; Tibboel, Dick; de Klein, Annelies

    2014-08-01

    Esophageal Atresia (EA) is a severe developmental defect of the foregut that presents with or without a Tracheo-Esophageal Fistula (TEF). The prevalence of EA/TEF over time and around the world has been relatively stable. EA/TEF is manifested in a broad spectrum of anomalies: in some patients it manifests as an isolated atresia or fistula, but in over half it affects several organ systems. While the associated malformations are often those of the VACTERL spectrum (Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal and Limb), many patients are affected by other malformations, such as microcephaly, micrognathia, pyloric stenosis, duodenal atresia, a single umbilical artery, and anomalies of the genitourinary, respiratory and gastrointestinal systems. Though EA/TEF is a genetically heterogeneous condition, recurrent genes and loci are sometimes affected. Tracheo-Esophageal (TE) defects are in fact a variable feature in several known single gene disorders and in patients with specific recurrent Copy Number Variations and structural chromosomal aberrations. At present, a causal genetic aberration can be identified in 11-12% of patients. In most, EA/TEF is a sporadic finding; the familial recurrence rate is low (1%). As this suggests that epigenetic and environmental factors also contribute to the disease, non-syndromic EA/TEF is generally believed to be a multifactorial condition. Several population-based studies and case reports describe a wide range of associated risks, including age, diabetes, drug use, herbicides, smoking and fetal alcohol exposure. The phenotypical and genetic heterogeneity seen in EA/TEF patients indicates not one underlying cause, but several. Unraveling the complex multifactorial and heterogeneous etiology of EA/TEF and associated features will require large cohorts of patients. Combined statistical analysis of component findings, genome sequencing, and genome wide association studies will elucidate new causal genetic defects and predisposing loci in the etiology within specific sub-populations. Improved knowledge of environmental risk factors, genetic predisposition and causal genetic syndromes may improve prediction and parental counseling, and prevent co-morbidity. PMID:24931924

  17. Esophageal squamous cell cancer in a highly endemic region

    PubMed Central

    Asombang, Akwi W; Kayamba, Violet; Lisulo, Mpala M; Trinkaus, Kathryn; Mudenda, Victor; Sinkala, Edford; Mwanamakondo, Stayner; Banda, Themba; Soko, Rose; Kelly, Paul

    2016-01-01

    AIM: To identify risk factors associated with esophageal cancer in Zambia and association between dietary intake and urinary 8-iso prostaglandin F2α (8-isoPGF2α). METHODS: We conducted a prospective, case control study at the University Teaching Hospital. Subjects included both individuals admitted to the hospital and those presenting for an outpatient upper endoscopy. Esophageal cancer cases were compared to age and sex-matched controls. Cases were defined as patients with biopsy proven esophageal cancer; controls were defined as subjects without endoscopic evidence of esophageal cancer. Clinical and dietary data were collected using a standard questionnaire, developed a priori. Blood was collected for human immunodeficiency virus (HIV) serology. Urine was collected, and 8-isoPGF2α was measured primarily by enzyme-linked immunosorbent assay and expressed as a ratio to creatinine. RESULTS: Forty five controls (mean age 54.2 ± 15.3, 31 male) and 27 cases (mean age 54.6 ± 16.4, 17 males) were studied. Body mass index was lower in cases (median 16.8) than controls (median 23.2), P = 0.01. Histopathologically, 25/27 (93%) were squamous cell carcinoma and 2/27 (7%) adenocarcinoma. More cases smoked cigarettes (OR = 11.24, 95%CI: 1.37-92.4, P = 0.02) but alcohol consumption and HIV seropositivity did not differ significantly (P = 0.14 for both). Fruit, vegetables and fish consumption did not differ significantly between groups (P = 0.11, 0.12, and 0.10, respectively). Mean isoprostane level was significantly higher in cases (0.03 ng/mg creatinine) than controls (0.01 ng/mg creatinine) (OR = 2.35, 95%CI: 1.19-4.65, P = 0.014). CONCLUSION: Smoking and isoprostane levels were significantly associated with esophageal cancer in Zambians, but diet, HIV status, and alcohol consumption were not. PMID:26973419

  18. Meat consumption and risk of esophageal and gastric cancer in a large prospective study

    PubMed Central

    Cross, Amanda J.; Freedman, Neal D.; Ren, Jiansong; Ward, Mary H.; Hollenbeck, Albert R.; Schatzkin, Arthur; Sinha, Rashmi; Abnet, Christian C.

    2010-01-01

    Background Red and processed meats could increase cancer risk via several potential mechanisms involving iron, heterocyclic amines, polycyclic aromatic hydrocarbons and N-nitroso compounds. Although there have been multiple studies of meat and colorectal cancer, other gastrointestinal malignancies are understudied. Methods We estimated hazards ratios (HR) and 95% confidence intervals (CI) for the association between meat, meat components, and meat cooking by-products and risk of esophageal or gastric cancer in a large cohort study. During approximately 10 years of follow-up, we accrued 215 esophageal squamous cell carcinomas, 630 esophageal adenocarcinomas, 454 gastric cardia adenocarcinomas and 501 gastric non-cardia adenocarcinomas. Results Red meat intake was positively associated with esophageal squamous cell carcinoma (HR for the top versus bottom quintile = 1.79, 95% CI: 1.07–3.01, P for trend = 0.019). Individuals in the highest intake quintile of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) had an increased risk for gastric cardia cancer (HR = 1.44, 95% CI: 1.01–2.07, P for trend = 0.104). Furthermore, those in the highest quintile of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) or heme iron intake had a suggestive increased risk for esophageal adenocarcinoma (HR = 1.35, 95% CI: 0.97–1.89, P for trend = 0.022; HR = 1.45, 95% CI: 0.99–2.12, P for trend = 0.463; HR = 1.47, 95% CI: 0.99-2.20, P for trend = 0.063, respectively). Benzo[a]pyrene, nitrate and nitrite were not associated with esophageal or gastric cancer. Conclusions We found positive associations between red meat intake and esophageal squamous cell carcinoma, and between DiMeIQx intake and gastric cardia cancer. PMID:20978481

  19. A Unique Case of a Patient with Rectal Cancer Who Developed Benign Esophageal Stenosis after Localized Rectal Radiation and Systemic Chemotherapy

    PubMed Central

    Chahla, Elie; Cheesman, Antonio; Hammami, Muhammad; Taylor, Jason R.; Poddar, Nishant; Garrett, Robert W.; Alkaade, Samer

    2015-01-01

    Acute esophagitis and esophageal strictures typically occur after local radiation therapy to the thoracic field. Toxicity is usually limited to the field of radiation and potentially augmented by concomitant use of chemotherapy, however esophageal stricturing due to chemotherapy alone is exceedingly rare. Gastrointestinal toxicity has been previously reported in the setting of 5-fluorouracil (5-FU)-based chemotherapy with abnormal thymidylate synthase or dihydropyrimidine dehydrogenase activities. We present a unique case of isolated chemotherapy-induced esophageal stricture in the setting of stage IIIa rectal adenocarcinoma which presented shortly after initiation of treatment with 5-FU-based chemotherapy in a patient with normal thymidylate synthase and dihydropyrimidine dehydrogenase assays. These findings prompt further investigation of pathways and potential risk factors leading to esophageal toxicity in patients treated with 5-FU-based chemotherapy. PMID:25802497

  20. Esophageal trichomoniasis in chickens.

    PubMed

    Willoughby, D H; Bickford, A A; Charlton, B R; Cooper, G L

    1995-01-01

    Esophageal trichomoniasis has been rarely reported in chickens. At the California Veterinary Diagnostic Laboratory System-Turlock Branch, this disease was recently diagnosed in two cases submitted from backyard chicken flocks. The esophageal lesions observed were similar to those seen in several other important diseases of chickens. The causative trichomonad organisms were readily demonstrated on wet smears and by histologic studies. In both cases, the investigated flocks were afflicted with several concurrent diseases. California has experienced an increase in the number of small nontraditional chicken production operations. These facilities are sometimes in close proximity to commercial poultry operations and biosecurity barriers occasionally fail. The poor husbandry practices often used in these small flocks make them a potential reservoir for rare diseases such as trichomoniasis and also for disease organisms that are devastating to commercial poultry. PMID:8719231

  1. Esophagojejunal anastomosis fistula, distal esophageal stenosis, and metalic stent migration after total gastrectomy.

    PubMed

    Al Hajjar, Nadim; Popa, Calin; Al-Momani, Tareg; Margarit, Simona; Graur, Florin; Tantau, Marcel

    2015-01-01

    Esophagojejunal anastomosis fistula is the main complication after a total gastrectomy. To avoid a complex procedure on friable inflamed perianastomotic tissues, a coated self-expandable stent is mounted at the site of the anastomotic leak. A complication of stenting procedure is that it might lead to distal esophageal stenosis. However, another frequently encountered complication of stenting is stent migration, which is treated nonsurgically. When the migrated stent creates life threatening complications, surgical removal is indicated. We present a case of a 67-year-old male patient who was treated at our facility for a gastric adenocarcinoma which developed, postoperatively, an esophagojejunostomy fistula, a distal esophageal stenosis, and a metallic coated self-expandable stent migration. To our knowledge, this is the first reported case of an esophagojejunostomy fistula combined with a distal esophageal stenosis as well as with a metallic coated self-expandable stent migration. PMID:25945277

  2. Esophagojejunal Anastomosis Fistula, Distal Esophageal Stenosis, and Metalic Stent Migration after Total Gastrectomy

    PubMed Central

    Al Hajjar, Nadim; Popa, Calin; Al-Momani, Tareg; Margarit, Simona; Graur, Florin; Tantau, Marcel

    2015-01-01

    Esophagojejunal anastomosis fistula is the main complication after a total gastrectomy. To avoid a complex procedure on friable inflamed perianastomotic tissues, a coated self-expandable stent is mounted at the site of the anastomotic leak. A complication of stenting procedure is that it might lead to distal esophageal stenosis. However, another frequently encountered complication of stenting is stent migration, which is treated nonsurgically. When the migrated stent creates life threatening complications, surgical removal is indicated. We present a case of a 67-year-old male patient who was treated at our facility for a gastric adenocarcinoma which developed, postoperatively, an esophagojejunostomy fistula, a distal esophageal stenosis, and a metallic coated self-expandable stent migration. To our knowledge, this is the first reported case of an esophagojejunostomy fistula combined with a distal esophageal stenosis as well as with a metallic coated self-expandable stent migration. PMID:25945277

  3. Laparoscopic transhiatal approach for resection of an adenocarcinoma in long-segment Barrett’s esophagus

    PubMed Central

    Shiozaki, Atsushi; Fujiwara, Hitoshi; Konishi, Hirotaka; Kinoshita, Osamu; Kosuga, Toshiyuki; Morimura, Ryo; Murayama, Yasutoshi; Komatsu, Shuhei; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Okamoto, Kazuma; Sakakura, Chouhei; Otsuji, Eigo

    2015-01-01

    Barrett’s esophagus (BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long-segment BE (LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach (LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of the arch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 mL of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis. PMID:26269688

  4. Biology of Telomeres: Importance in Etiology of Esophageal Cancer And As Therapeutic Target

    PubMed Central

    Pal, Jagannath; Gold, Jason S.; Munshi, Nikhil C.; Shammas, Masood A.

    2013-01-01

    Purpose of review The purpose of this review is to highlight the importance of telomeres, the mechanisms implicated in their maintenance, and their role in the etiology as well as the treatment of human esophageal cancer. We will also discuss the role of telomeres in the maintenance/preservation of genomic integrity, the consequences of telomere dysfunction, and the various factors that may affect telomere health in esophageal tissue predisposing it to oncogenesis. Recent findings There has been growing evidence that telomeres, which can be affected by various intrinsic and extrinsic factors, contribute to genomic instability, oncogenesis, as well as proliferation of cancer cells. Summary Telomeres are the protective DNA-protein complexes at chromosome ends. Telomeric DNA undergoes progressive shortening with age leading to cellular senescence and/or apoptosis. If senescence/apoptosis is prevented as a consequence of specific genomic changes, continued proliferation leads to very short (i.e. dysfunctional) telomeres that can potentially cause genomic instability thus increasing the risk for activation of telomere maintenance mechanisms and oncogenesis. Like many other cancers, esophageal cancer cells have short telomeres and elevated telomerase, the enzyme that maintains telomeres in most cancer cells. Homologous recombination, which is implicated in the alternate pathway of telomere elongation, is also elevated in Barrett’s-associated esophageal adenocarcinoma. Evidence from our laboratory indicates that both telomerase and homologous recombination contribute to telomere maintenance, DNA repair, and the ongoing survival of esophageal cancer cells. This indicates that telomere maintenance mechanisms may potentially be targeted to make esophageal cancer cells static. The rate at which telomeres in healthy cells shorten is determined by a number of intrinsic and extrinsic factors, including those associated with lifestyle. Avoidance of factors that may directly or indirectly injure esophageal tissue including its telomeric and other genomic DNA can not only reduce the risk of development of esophageal cancer but may also have positive impact on overall health and lifespan. PMID:24090770

  5. Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett's esophagus.

    PubMed

    Phillips, Wayne A; Russell, Sarah E; Ciavarella, Marianne L; Choong, David Y H; Montgomery, Karen G; Smith, Katherine; Pearson, Richard B; Thomas, Robert J S; Campbell, Ian G

    2006-05-15

    Mutation of PIK3CA, the gene coding for the p110alpha catalytic subunit of phosphoinositide 3-kinase (PI3K), has been reported in a limited range of human tumors. We now report that PIK3CA is also mutated in esophageal tumors. Single-strand conformational polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) were used to screen all 20 exons of PIK3CA in 101 samples from 95 individuals with esophageal cancer and/or Barrett's esophagus. Somatic mutation of PIK3CA was detected in 4 of 35 (11.8%) of esophageal squamous cell carcinomas (SCC) and 3 of 50 (6%) adenocarcinomas. No mutations were detected in any of 17 samples of Barrett's esophagus. For PIK3CB, we screened exons 11 and 22, which code for the regions corresponding to the exon 9 and 20 mutational 'hotspots' of PIK3CA. No somatic changes were detected in PIK3CB This study extends previous observations in other tumor types by demonstrating the presence of somatic PIK3CA mutations in both SCC and adenocarcinoma of the esophagus, thus implicating the PI3K pathway in the initiation and/or progression of esophageal cancers. PMID:16380997

  6. Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: First in-human results

    PubMed Central

    Sturm, Matthew B.; Joshi, Bishnu P.; Lu, Shaoying; Piraka, Cyrus; Khondee, Supang; Elmunzer, B. Joseph; Kwon, Richard S.; Beer, David G.; Appelman, Henry; Turgeon, D. Kim; Wang, Thomas D.

    2013-01-01

    Esophageal adenocarcinoma is rising rapidly in incidence, and usually develops from Barrett’s esophagus, a precursor condition commonly found in patients with chronic acid reflux. Pre-malignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett’s esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-humans results show that this targeted imaging agent is safe, and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach. PMID:23658246

  7. Solid adenocarcinoma

    Cancer.gov

    Uniformly solid character of the lesions is usually indicative of a well differentiated tumor. No solid adenocarcinomas have observed in our series. However, rare cases have been described by others. In human pathology this diagnosis is usually based on detection of mucin after periodic acid-Schiff reaction with diastase (α-amylase) digestion.

  8. Apocrine adenocarcinoma of the vulva.

    PubMed

    Kajal, Babita; Talati, Hetal; Daya, Dean; Alowami, Salem

    2013-01-01

    Cutaneous vulvar carcinomas are predominantly of squamous cell carcinoma type. Primary vulvar adenocarcinomas are rare with a poorly understood histogenesis. They are classified into extramammary Paget's disease, sweat gland carcinomas, and breast-like adenocarcinomas of the vulva. Adenocarcinomas, originating from Bartholin glands, can also present as vulvar adenocarcinoma. Rare adenocarcinomas with apocrine features have been described in the literature. The origin of these neoplasms from the native apocrine sweat glands or from anogenital mammary-like glands is still debatable. We report herein a case of a 67 year old female with a rare primary apocrine carcinoma of the vulva. PMID:24179652

  9. Genetics Home Reference: esophageal atresia/tracheoesophageal fistula

    MedlinePlus

    ... Tracheoesophageal Fistula and Esophageal Atresia Repair Health Topic: Esophagus Disorders Educational Resources (2 links) MalaCards: esophageal atresia/tracheoesophageal fistula Orphanet: Esophageal atresia Patient Support ...

  10. Associated congenital anomalies between neonates with short-gap and long-gap esophageal atresia: a comparative study

    PubMed Central

    Aslanabadi, Saeid; Ghabili, Kamyar; Rouzrokh, Mohsen; Hosseini, Mohammad Bagher; Jamshidi, Masoud; Adl, Farzad Hami; Shoja, Mohammadali M

    2011-01-01

    Background: Predicting the presence of long-gap esophageal atresia (EA) prior to the surgery is of clinical importance. No comparison between short-gap and long-gap EA for the prevalence of VACTERL and non-VACTERL-type anomalies has yet been performed. Objective: The aim of this study was to compare VACTERL and non-VACTERL-type anomalies between patients with short-gap and long-gap EA. Methods: Retrospectively, medical records of all newborns managed for EA/tracheoesophageal fistula (TEF) in Tabriz Children’s Hospital and Tehran Mofid Hospital between 2007 and 2010 were evaluated. Demographic data and associated anomalies including both the VACTERL and non-VACTERL-type defects were listed. The VACTERL spectrum defects covered vertebral/costal, anorectal, cardiovascular, TEF, and renal- or radial-type limb anomalies. The non-VACTERL-type anomalies included hydrocephalus, orofacial defects, respiratory system anomalies, gastrointestinal anomalies, genital anomalies, and non-VACTERL limb defects. Demographic data, and the VACTERL and non-VACTERL-type anomalies were compared among children with long-gap EA and those with short-gap EA. Results: Two hundred and seventy-six children were included in the study: 230 (83.3%) in the short-gap EA group and 46 (16.7%) in the long-gap EA group. Although prevalence of the VACTERL spectrum anomalies did not differ between the two groups, the non-VACTERL anomaly was more common in the long-gap EA group (P = 0.02). Among the VACTERL-type defects, TEF was detected in 30 (65.2%) and 218 (94.7%) patients in long-gap and short-gap EA groups, respectively (P = 0.0001). Conclusion: The non-VACTERL-type anomalies, but not the VACTERL spectrum defects, are more frequent in patients with long-gap EA than those with short-gap EA. PMID:21760750

  11. Gender difference in gastro-esophageal reflux diseases

    PubMed Central

    Asanuma, Kiyotaka; Iijima, Katsunori; Shimosegawa, Tooru

    2016-01-01

    The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett’s esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen. PMID:26855539

  12. Manometric features of Eosinophilic Esophagitis in Esophageal Pressure Topography

    PubMed Central

    Roman, Sabine; Hirano, Ikuo; Kwiatek, Monika A; Gonsalves, Nirmala; Chen, Joan; Kahrilas, Peter J; Pandolfino, John E

    2010-01-01

    Backgrounds Although most patients with EoE have mucosal and structural changes that could potentially explain their symptoms, it is unclear whether EoE is associated with abnormal esophageal motor function. The aims of this study were to evaluate the esophageal pressure topography (EPT) findings in EoE and to compare them with controls and patients with gastro-esophageal disease (GERD). Methods EPT studies in 48 EoE patients, 48 GERD patients and 50 controls were compared. The esophageal contractile pattern was described for ten 5-ml swallows for each subject and each swallow was secondarily characterized based on the bolus pressurization pattern: absent, pan-esophageal pressurization, or compartmentalized distal pressurization. Key Results 37% of EoE patients were classified as having abnormal esophageal motility. The most frequent diagnoses were of weak peristalsis and frequent failed peristalsis. Although motility disorders were more frequent in EoE patients than in controls, the prevalence and type were similar to those observed in GERD patients (p=0.61, Chi square test). Pan-esophageal pressurization was present in 17% of EoE and 2% of GERD patients while compartmentalized pressurization was present in 19% of EoE and 10% of GERD patients. These patterns were not seen in control subjects. Conclusions & Inferences The prevalence of abnormal esophageal motility in EoE was approximately 37% and was similar in frequency and type to motor patterns observed in GERD. EoE patients were more likely to have abnormal bolus pressurization patterns during swallowing and we hypothesize that this may be a manifestation of reduced esophageal compliance. PMID:21091849

  13. Gastro-esophageal reflux time parameters and esophagitis in children

    SciTech Connect

    Baulieu, F.; Baulieu, J.; Maurage, C.; Casset, D.; Itti, R.

    1985-05-01

    The aim of this work was to study the correlation between the reflux timing and the presence of esophagitis, an inconstant but serious complication of gastro-esophageal reflux (GER). The hypothesis was that reflux occurring late after meal can be incriminated more than early reflux in esophagitis genesis. 32 children with GER (mean age = 10.5 months, 2 to 30 months) had esophagoscopy and scintigraphy in the same week. The children were classified in two groups according to esophagoscopy: group 1 (n = 18) no esophagitis, group 2 (n = 14) esophaqgitis. The scintigraphy involved the ingestion of 0.5 mCi Tc-99m sulfur colloid milk mixture, followed by esophageal and gastric activity recording (one image per minute for 1 hour). The reflux was assessed from contrast enhanced images and esophageal time activity curves. Reflux intensity was quantitated by reflux index (Re). Mean reflux time was calculated as the mean esophageal activity peaks time (t-bar). Finally a composite parameter was calculated as the mean reflux time weighted by the relative intensity of each reflux peak (t-barw). Re was not found to be different between the two groups. t-bar was significantly higher in group 2: t-bar = 29.6 +- 3.0 mn (mean +- SD) than in group 1: t-bar = 24.5 +- 6.8 mn; rho <0.02. The difference between the two groups was enhanced by intensity weighting: group 1: t-barw = 16.6 +- 6.3 mn, group 2: t-barw = 33.5 +- 7.1 mn rho <0.001. t-barw value was not correlated to esophagitis grade. These results suggest that late reflux is more likely responsible of esophagitis.

  14. [Chemoprevention in adenocarcinoma of the esophagus].

    PubMed

    Lanas, Angel; Alcedo González, Javier

    2007-03-01

    The incidence of the adenocarcinoma of the esophagus (ACE) has dramatically for the last decades in western countries, which has been associated with a parallel increase in the incidence and prevalence of symptoms associated with gastroesophageal reflux diseases (GERD) and Barrett's esophagus (BE). Both conditions are now considered risk factors for ACE. Different pathways, including overexpression of cyclooxygenase (COX) isoenzymes, has been proposed to explain the carcinogenic process leading from normal esophagus to esophagitis, BE and ACE. The survival rate in patients with ACE is very low because of the poor outcomes of surgery and the limited benefits obtained with concomitant chemo-radiotherapy Several strategies based on early detection and surveillance of preneoplastic lessions have failed to have a global and significant impact on the prognosis of the ACE. Recent epidemiological and experimental studies suggest that chemoprevention could be useful in the management of patients with GERD and especially in those with BE. The current therapy with protom pump inhibitors (PPI) is effective to reduce the esophageal acid exposure, to improve reflux symptoms, and to heal inflammatory injuries, but probably is not enough to avoid the dysplastic progression of the metaplastic epithelium. Regular use of COX inhibitors (aspirin and other non steroid antiinflamatory drugs) has been associated with reduction of the risk of ACE and to decrease the incidence of ACE in animal models. In humans, the association of PPI with COX inhibitors could be a cost-effectiveness strategy but direct evidence is lacking. Other potential agents that have shown some chemoprevention potential include troglitazone, free radical scavengers, tamoxifen or prostaglandin receptor blockers, but the available scientific evidence is still poor and not ready to be tested in humans. PMID:17486744

  15. Src Mutation Induces Acquired Lapatinib Resistance in ERBB2-Amplified Human Gastroesophageal Adenocarcinoma Models

    PubMed Central

    Hong, Yong Sang; Kim, Jihun; Pectasides, Eirini; Fox, Cameron; Hong, Seung-Woo; Ma, Qiuping; Wong, Gabrielle S.; Peng, Shouyong; Stachler, Matthew D.; Thorner, Aaron R.; Van Hummelen, Paul; Bass, Adam J.

    2014-01-01

    ERBB2-directed therapy is now a routine component of therapy for ERBB2-amplified metastatic gastroesophageal adenocarcinomas. However, there is little knowledge of the mechanisms by which these tumors develop acquired resistance to ERBB2 inhibition. To investigate this question we sought to characterize cell line models of ERBB2-amplified gastroesophageal adenocarcinoma with acquired resistance to ERBB2 inhibition. We generated lapatinib-resistant (LR) subclones from an initially lapatinib-sensitive ERBB2-amplified esophageal adenocarcinoma cell line, OE19. We subsequently performed genomic characterization and functional analyses of resistant subclones with acquired lapatinib resistance. We identified a novel, acquired SrcE527K mutation in a subset of LR OE19 subclones. Cells with this mutant allele harbour increased Src phosphorylation. Genetic and pharmacologic inhibition of Src resensitized these subclones to lapatinib. Biochemically, Src mutations could activate both the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways in the lapatinib-treated LR OE19 cells. Ectopic expression of Src E527K mutation also was sufficient to induce lapatinib resistance in drug-naïve cells. These results indicate that pathologic activation of Src is a potential mechanism of acquired resistance to ERBB2 inhibition in ERBB2-amplified gastroesophageal cancer. Although Src mutation has not been described in primary tumor samples, we propose that the Src hyperactivation should be investigated in the settings of acquired resistance to ERBB2 inhibition in esophageal and gastric adenocarcinoma. PMID:25350844

  16. Esophageal cancer management controversies: Radiation oncology point of view

    PubMed Central

    Tai, Patricia; Yu, Edward

    2014-01-01

    Esophageal cancer treatment has evolved from single modality to trimodality therapy. There are some controversies of the role, target volumes and dose of radiotherapy (RT) in the literature over decades. The present review focuses primarily on RT as part of the treatment modalities, and highlight on the RT volume and its dose in the management of esophageal cancer. The randomized adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction. They were randomly assigned to surgery plus postoperative CRT or surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result. Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists. Pre-operative and post-operative target volumes are designed to optimize for disease control. Esophageal brachytherapy is effective in the palliation of dysphagia, but should not be given concomitantly with chemotherapy or external beam RT. The role of brachytherapy in multimodality management requires further investigation. On-going studies of multidisciplinary treatment in locally advanced cancer include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of life analysis). These trials hopefully will shed more light on the future management of esophageal cancer. PMID:25132924

  17. Esophageal cancer: A Review of epidemiology, pathogenesis, staging workup and treatment modalities

    PubMed Central

    Napier, Kyle J; Scheerer, Mary; Misra, Subhasis

    2014-01-01

    Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstays of current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy. PMID:24834141

  18. Impact of histone deacetylase 1 and metastasis-associated gene 1 expression in esophageal carcinogenesis.

    PubMed

    Miyashita, Tomoharu; Tajima, Hidehiro; Munemoto, Masayoshi; Shah, Furhawn A; Harmon, John W; Watanabe, Toshifumi; Shoji, Masatoshi; Okamoto, Koichi; Nakanuma, Shinichi; Sakai, Seisho; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Hayashi, Hironori; Oyama, Katsunobu; Inokuchi, Masafumi; Nakagawara, Hisatoshi; Takamura, Hiroyuki; Ninomiya, Itasu; Kitagawa, Hirohisa; Fushida, Sachio; Mukaisho, Kenichi; Fujimura, Takashi; Ohta, Tetsuo

    2014-08-01

    Animal models are important for the development of novel therapies for esophageal cancer. Histone deacetylase 1 (HDAC1)/metastasis-associated gene (MTA1) complexes inhibit p53 acetylation and thus, inhibit p53-induced apoptosis. The aim of the present study was to evaluate HDAC1 and MTA1 expression in esophageal carcinogenesis in rats. The rats underwent a total gastrectomy followed by esophagojejunostomy to induce chronic duodenal content reflux esophagitis. The rats were sacrificed sequentially at 20, 30, 40 and 50 weeks post-surgery and the esophagi were examined. Immunohistochemical analysis was conducted to assess the expression and localization of HDAC1 and MTA1. At 20 weeks post-surgery, squamous proliferative hyperplasia and Barrett's metaplasia (BM) were observed. While, adenocarcinoma-associated BM and squamous cell carcinoma were observed at 30-50 weeks post-surgery. The nuclear expression of HDAC1 and MTA1 was observed in all of the stages of squamous carcinogenesis and adenocarcinogenesis, although not in the normal esophageal epithelium. The expression of HDAC1 and MTA1 may be involved in duodenoesophageal reflux-induced neoplastic transformation of the esophageal mucosa into cancer cells with squamous and adeno differentiation. PMID:25009653

  19. [Brachytherapy in prostatic adenocarcinoma].

    PubMed

    Haie-Meder, C; Court, B; Perrin, J L; Wibault, P; Lartigau, E; Gerbaulet, A

    1994-01-01

    Brachytherapy can represent the exclusive treatment of localized prostatic adenocarcinoma. Several techniques have been described: permanent implantations with 125-iodine or 198-gold seeds or temporary implantations with 192-iridium. These implantations are performed either via a retropubic approach, often combined with pelvic lymphadenectomy, or via a transperineal approach, with or without ultrasound guidance. The largest clinical experience is from Memorial Sloan-Kettering Cancer Center, with 1119 patients treated from 1970 to 1985 for stage B or C prostatic adenocarcinoma with pelvic lymph node dissection and interstitial iodine-125 brachytherapy. The 15-year overall local control is 51%. One of the strongest prognostic factors is lymph node involvement. The comparison between brachytherapy and other treatment modalities such as radical prostatectomy or external irradiation or even expectant management in localized tumors has never been performed prospectively. This type of randomized trial appears to be necessary in the assessment of the results published with brachytherapy. PMID:7893114

  20. Esophageal impacted dentures.

    PubMed Central

    Nwaorgu, Onyekwere G.; Onakoya, Paul A.; Sogebi, Olusola A.; Kokong, Daniel D.; Dosumu, Oluwole O.

    2004-01-01

    OBJECTIVES: This study aims to highlight the problems associated with impacted acrylic dentures and proffers advice to check them. PATIENTS AND METHODS: Retrospective review of all cases of impacted acrylic dentures over a 16-year period. RESULTS: Twenty-two adults had impacted esophageal acrylic dentures of which 16 (72.7%) and six (27.3%) were males and females, respectively (M:F ratio = 2.7:1) with age range 23-77 years. Fourteen patients (63.6%) had worn their dentures for more than 10 years without check-up, and 54.5% presented within 48 hours of impaction. The common symptoms in all the patients were difficulty with swallowing, throat pain and discomfort, followed by tenderness in the neck in 15 (68.2%). Dentures were extracted through esophagoscopy (17 cases) and cervical (three cases) esophagotomy, respectively. Observed complications included pulmonary edema in one and esophageal perforation in five patients. CONCLUSION: Endoscopic extraction of dentures carries a high risk of perforation. Extraction of an impacted denture via esophagoscopy can be undertaken under direct vision and in an ideal situation with judicious use of the Shears forceps. In the absence of these, the safest option is an esophagotomy. Proper treatment planning in the fabrication of dentures with incorporation of radiopaque materials in the dental resins and adequate postdenture delivery instructions are necessary as preventive measures. PMID:15540888

  1. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract.

    PubMed

    Matuschek, C; Bölke, Edwin; Peiper, M; Knoefel, W T; Budach, W; Erhardt, A; Scherer, A; Gerber, P A; Buhren, B A; Gattermann, N; Baldus, S E; Rusnak, E; Shukla, V; Orth, K

    2011-06-21

    Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemo?radiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection. PMID:21810561

  2. The role of neoadjuvant and adjuvant treatment for adenocarcinoma of the upper gastrointestinal tract

    PubMed Central

    2011-01-01

    Both locally advanced adenocarcinoma of the stomach and gastro-esophageal junction are associated with poor prognosis due to the lack of effective treatment. Recently multimodal treatment consisting of neoadjuvant chemotherapy in combination with radiotherapy is reported to improve survival when compared to surgery alone. Neoadjuvant therapy in these locally advanced tumors allows for early tumor responses and the extent of tumor regression that can be achieved is considered a significant prognostic factor. This, in turn, increases the resectability of these tumors. Also due to the high frequency of lymph node metastasis, patients with locally advanced adenocarcinoma should undergo a D2 lymphadenectomy. Postoperative chemoradiation and perioperative chemotherapy have been studied in gastric adenocarcinomas and showed a survival benefit. However, the surgical techniques used in these trials are no longer considered to be standard by today's surgical practice. In addition, there are no standard recommendations for adjuvant chemotherapy or chemoradiation after R0 resection and adequate lymph node dissection. PMID:21810561

  3. Nuclear medicine and esophageal surgery

    SciTech Connect

    Taillefer, R.; Beauchamp, G.; Duranceau, A.C.; Lafontaine, E.

    1986-06-01

    The principal radionuclide procedures involved in the evaluation of esophageal disorders that are amenable to surgery are illustrated and briefly described. The role of the radionuclide esophagogram (RE) in the diagnosis and management of achalasia, oculopharyngeal muscular dystrophy and its complications, tracheoesophageal fistulae, pharyngeal and esophageal diverticulae, gastric transposition, and fundoplication is discussed. Detection of columnar-lined esophagus by Tc-99m pertechnetate imaging and of esophageal carcinoma by Ga-67 citrate and Tc-99m glucoheptonate studies also is presented. 37 references.

  4. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General § 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential messages. (b) Local Primary (LP) is a source of EAS Local Area messages. An...

  5. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol...

  6. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol...

  7. Esophageal tissue engineering: a new approach for esophageal replacement.

    PubMed

    Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

    2012-12-21

    A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed. PMID:23322987

  8. Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis

    PubMed Central

    2014-01-01

    Background Esophageal cancer ranks eighth among frequent cancers worldwide. Our aim was to investigate whether and at which neoplastic stage promoter hypermethylation of CAV1 is involved in human esophageal carcinogenesis. Methods Using real-time quantitative methylation-specific PCR (qMSP), we examined CAV1 promoter hypermethylation in 260 human esophageal tissue specimens. Real-time RT-PCR and qMSP were also performed on OE33 esophageal cancer cells before and after treatment with the demethylating agent, 5-aza-2’-deoxycytidine (5-Aza-dC). Results CAV1 hypermethylation showed highly discriminative ROC curve profiles, clearly distinguishing esophageal adenocarcinomas (EAC) and esophageal squamous cell carcinomas (ESCC) from normal esophagus (NE) (EAC vs. NE, AUROC = 0.839 and p < 0.0001; ESCC vs. NE, AUROC = 0.920 and p < 0.0001). Both CAV1 methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett’s metaplasia (BE), low-grade and high-grade dysplasia occurring in BE (D), EAC, and ESCC than in NE (all p < 0.01, respectively). Meanwhile, among 41 cases with matched NE and EAC or ESCC, CAV1 NMVs in EAC and ESCC (mean = 0.273) were significantly higher than in corresponding NE (mean = 0.146; p < 0.01, Student’s paired t-test). Treatment of OE33 EAC cells with 5-Aza-dC reduced CAV1 methylation and increased CAV1 mRNA expression. Conclusions CAV1 promoter hypermethylation is a frequent event in human esophageal carcinomas and is associated with early neoplastic progression in Barrett’s esophagus. PMID:24885118

  9. Cutaneous metastasis in anorectal adenocarcinoma.

    PubMed

    Varma, Krishnendra; Singh, Ujjwal Kumar; Jain, Mansi; Dhand, P L

    2015-01-01

    Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum) of a metastatic adenocarcinoma. PMID:26009722

  10. Cutaneous metastasis in anorectal adenocarcinoma

    PubMed Central

    Varma, Krishnendra; Singh, Ujjwal Kumar; Jain, Mansi; Dhand, P. L.

    2015-01-01

    Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum) of a metastatic adenocarcinoma. PMID:26009722

  11. Drugs Approved for Esophageal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  12. Targeted therapy in esophageal cancer.

    PubMed

    Zhang, Lei; Ma, Jiaojiao; Han, Yu; Liu, Jinqiang; Zhou, Wei; Hong, Liu; Fan, Daiming

    2016-05-01

    An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer. PMID:26895097

  13. Endoscopic and clinicopathological patterns of esophageal cancer in Tanzania: experiences from two tertiary health institutions

    PubMed Central

    2013-01-01

    Background Esophageal cancer is one of the most serious gastrointestinal cancer worldwide, owing to its rapid development and fatal prognoses in most cases. There is a paucity of published data regarding esophageal cancer in Tanzania and the study area in particular. This study was conducted to describe the endoscopic and clinicopathological patterns of esophageal cancer in this part of the world. The study provides baseline local data for future comparison. Methods This was a retrospective study of histologically confirmed cases of esophageal cancer seen at Bugando Medical Center and Muhimbili National Hospital between March 2008 and February 2013. Data were retrieved from medical record computer database and analyzed using SPSS computer software version 17.0. Results A total of 328 esophageal cancer patients were enrolled in the study, representing 25.3% of all malignant gastrointestinal tract tumors. The male to female ratio was 2.2:1. The median age of patients at presentation was 47 years. The majority of patients (86.6%) were peasants coming from the rural areas. Smoking and alcohol consumption were documented in 74.7% and 61.6% of patients respectively. Family history of esophageal cancer was reported in 4.6% of cases. The majority of patients (81.7%) presented late with advanced stage of cancer. Progressive dysphagia and weight loss were the most common presenting symptoms occurring in all patients. The middle third esophagus (58.5%) was the most frequent anatomical site for esophageal cancer followed by lower third (27.4%) and upper third esophagus (10.4%). Squamous cell carcinoma (96.0%) was the most common histopathological type. Adenocarcinoma occurred in 13 (4.0%) patients. TNM staging was documented in only 104 (31.7%) patients. Of these, 102(98.1%) patients were diagnosed with advanced esophageal cancer (Stages III and IV). According to tumor grading, most of tumors were moderately differentiated accounting for 56.1% of cases. Distant metastasis was documented in 43.3% of patients. Conclusion Esophageal cancer is not uncommon in this region and shows a trend towards a relative young age at presentation and the majority of patients present late with advanced stage. There is a need for screening of high-risk populations and detecting esophageal cancer at an early stage in order to improve chances for successful treatment and survival. PMID:24094270

  14. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  15. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  16. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  17. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  18. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  19. Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China

    PubMed Central

    2009-01-01

    Background Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse. Methods 600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated. Results Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.392.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.772.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.093.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.013.29). Conclusion These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis. PMID:19656375

  20. Esophageal cancer: Risk factors, screening and endoscopic treatment in Western and Eastern countries

    PubMed Central

    Domper Arnal, María José; Ferrández Arenas, Ángel; Lanas Arbeloa, Ángel

    2015-01-01

    Esophageal cancer is one of the most unknown and deadliest cancers worldwide, mainly because of its extremely aggressive nature and poor survival rate. Esophageal cancer is the 6th leading cause of death from cancer and the 8th most common cancer in the world. The 5-year survival is around 15%-25%. There are clear differences between the risk factors of both histological types that affect their incidence and distribution worldwide. There are areas of high incidence of squamous cell carcinoma (some areas in China) that meet the requirements for cost-effectiveness of endoscopy for early diagnosis in the general population of those areas. In Europe and United States the predominant histologic subtype is adenocarcinoma. The role of early diagnosis of adenocarcinoma in Barrett’s esophagus remains controversial. The differences in the therapeutic management of early esophageal carcinoma (high-grade dysplasia, T1a, T1b, N0) between different parts of the world may be explained by the number of cancers diagnosed at an early stage. In areas where the incidence is high (China and Japan among others) early diagnoses is more frequent and has led to the development of endoscopic techniques for definitive treatment that achieve very effective results with a minimum number of complications and preserving the functionality of the esophagus. PMID:26185366

  1. Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing.

    PubMed

    Sasaki, Yasushi; Tamura, Miyuki; Koyama, Ryota; Nakagaki, Takafumi; Adachi, Yasushi; Tokino, Takashi

    2016-02-21

    Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett's esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma (ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing (NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D and NFE2L2, which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC. PMID:26900290

  2. Genomic characterization of esophageal squamous cell carcinoma: Insights from next-generation sequencing

    PubMed Central

    Sasaki, Yasushi; Tamura, Miyuki; Koyama, Ryota; Nakagaki, Takafumi; Adachi, Yasushi; Tokino, Takashi

    2016-01-01

    Two major types of cancer occur in the esophagus: squamous cell carcinoma, which is associated with chronic smoking and alcohol consumption, and adenocarcinoma, which typically arises in gastric reflux-associated Barrett’s esophagus. Although there is increasing incidence of esophageal adenocarcinoma in Western counties, esophageal squamous cell carcinoma (ESCC) accounts for most esophageal malignancies in East Asia, including China and Japan. Technological advances allowing for massively parallel, high-throughput next-generation sequencing (NGS) of DNA have enabled comprehensive characterization of somatic mutations in large numbers of tumor samples. Recently, several studies were published in which whole exome or whole genome sequencing was performed in ESCC tumors and compared with matched normal DNA. Mutations were validated in several genes, including in TP53, CDKN2A, FAT1, NOTCH1, PIK3CA, KMT2D and NFE2L2, which had been previously implicated in ESCC. Several new recurrent alterations have also been identified in ESCC. Combining the clinicopathological characteristics of patients with information obtained from NGS studies may lead to the development of effective diagnostic and therapeutic approaches for ESCC. As this research becomes more prominent, it is important that gastroenterologist become familiar with the various NGS technologies and the results generated using these methods. In the present study, we describe recent research approaches using NGS in ESCC. PMID:26900290

  3. The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and migration properties: Implication for S100A4 protein

    SciTech Connect

    Bruyere, Emilie; Jonckheere, Nicolas; Frenois, Frederic; Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex ; Mariette, Christophe; Universite Lille-Nord de France, 1 place de Verdun, 59045 Lille Cedex; Department of Digestive and Oncological Surgery, University Hospital Claude Huriez, 1 place de Verdun, 59045 Lille Cedex ; Van Seuningen, Isabelle

    2011-09-23

    Highlights: {yields} Loss of MUC4 reduces proliferation of esophageal cancer cells. {yields} MUC4 inhibition impairs migration of esophageal cancer cells but not their invasion. {yields} Loss of MUC4 significantly reduces in vivo tumor growth. {yields} Decrease of S100A4 induced by MUC4 inhibition impairs proliferation and migration. -- Abstract: MUC4 is a membrane-bound mucin known to participate in tumor progression. It has been shown that MUC4 pattern of expression is modified during esophageal carcinogenesis, with a progressive increase from metaplastic lesions to adenocarcinoma. The principal cause of development of esophageal adenocarcinoma is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated by several bile acids present in reflux. In this report, our aim was thus to determine whether MUC4 plays a role in biological properties of human esophageal cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells) were established using a shRNA approach. In vitro (proliferation, migration and invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID mice) biological properties of shMUC4 cells were analyzed. Our results show that shMUC4 cells were less proliferative, had decreased migration properties and did not express S100A4 protein when compared with MUC4 expressing cells. Absence of MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a significant decrease in tumor size when cells did not express MUC4. Altogether, these data indicate that MUC4 plays a key role in proliferative and migrating properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4 mucin appears thus as a good therapeutic target to slow-down esophageal tumor progression.

  4. A Comprehensive Review of Esophageal Stents

    PubMed Central

    Hong, Jinwha; Lam-Tsai, Yvette; Gress, Frank

    2012-01-01

    Esophageal stents are important tools for palliative treatment of inoperable esophageal malignancies. With the development of multiple self-expandable stents, there are now several therapeutic options for managing benign and malignant esophageal diseases. This paper discusses the various types of esophageal stents currently available, indications for their placement, challenges and complications that gastroenterologists face when placing these stents, and some of the innovations that will become available in the near future. PMID:23293566

  5. Computed tomographic features of esophageal intramural pseudodiverticulosis

    SciTech Connect

    Pearlberg, J.L.; Sandler, M.A.; Madrazo, B.L.

    1983-04-01

    A patient wit esophageal intramural pseudodiverticulosis (EIPD) was examined with computed tomography (CT). CT demonstrated marked thichening of the esophageal wall, diffuse irregularity of the esophageal lumen, and intramural gas collections-features typical of this entity. In the proper clinical setting, CT can confirm the diagnosis of EIPD, especially when other studies are equivocal. However, this case also demonstrates some of the limitations of CT in differentiating benign and malignant esophageal disorders.

  6. Different Redox States in Malignant and Nonmalignant Esophageal Epithelial Cells and Differential Cytotoxic Responses to Bile Acid and Honokiol

    PubMed Central

    Chen, Gang; Izzo, Julie; Demizu, Yusuke; Wang, Feng; Guha, Sushovan; Wu, Xifeng; Hung, Mein-Chie; Ajani, Jaffer A.

    2009-01-01

    Abstract Esophageal adenocarcinoma (EAC) is a highly lethal cancer in western countries. EAC cells are believed to develop from esophageal epithelial cells through complex transformation processes involving inflammation and oxidative stress. The purpose of this study was to compare the redox status of malignant and nonmalignant esophageal epithelial cells and to test their responses to bile acid–induced oxidative stress and to treatment with honokiol (HNK), a natural product with anticancer activity. We demonstrated that esophageal adenocarcinoma cells express significantly higher levels of antioxidant molecules and were resistant to reactive oxygen species (ROS) stress induced by bile acid, but were sensitive to the cytotoxic action of HNK. Mechanistic study showed that HNK caused cancer cell death by disruption of mitochondrial transmembrane potential and was correlated with cyclophilin D (CypD) expression. Inhibition of CypD by cyclosporin A or abrogation of its expression by siRNA significantly suppressed the cytotoxicity of HNK, suggesting that CypD may be a key molecule that mediates the cytotoxicity. Our study suggests that the high antioxidant capacity in EAC cells confers on them the ability to survive the oxidative microenvironment in the reflux esophagus, and that HNK is a promising compound to kill the transformed cells preferentially. Antioxid. Redox Signal. 11, 1083–1095. PMID:19187006

  7. CT diagnosis of an esophageal foreign body

    SciTech Connect

    Gambia, J.L.; Heaston, D.K.; Ling, D.; Korobkin, M.

    1983-02-01

    Although of proven value in the diagnosis and treatment of esophageal malignancy, computed tomography (CT) has had limited application in the evaluation of benign esophageal disease. The first case of a CT-detected esophageal foreign body is reported. The foreign body, a piece of bone present for possibly 3 years, had escaped prior detection by plain chest radiography, barium swallow, and esophagoscopy.

  8. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610...) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal prosthesis. (a) Identification. An esophageal prosthesis is a rigid, flexible, or expandable tubular device...

  9. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610...) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal prosthesis. (a) Identification. An esophageal prosthesis is a rigid, flexible, or expandable tubular device...

  10. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610...) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal prosthesis. (a) Identification. An esophageal prosthesis is a rigid, flexible, or expandable tubular device...

  11. Esophageal fistula associated with intracavitary irradiation for esophageal carcinoma

    SciTech Connect

    Hishikawa, Y.; Tanaka, S.; Miura, T.

    1986-05-01

    Fifty-three patients with esophageal carcinoma were treated with high-dose-rate intracavitary irradiation following external irradiation. Ten patients developed esophageal fistula. Perforations were found in the bronchus (four), major vessels (four), pericardium (one), and mediastinum (one). The frequency of fistula occurrence in these patients was not remarkably different from that in 30 other patients treated only with greater than or equal to 50 Gy external irradiation. From the time of the development of esophageal fistula, intracavitary irradiation did not seem to accelerate the development of fistula. The fistulas in our ten patients proved to be associated with tumor, deep ulcer (created before intracavitary irradiation), chemotherapy, infection, and trauma rather than the direct effect of intracavitary irradiation.

  12. The Pathophysiology of Eosinophilic Esophagitis

    PubMed Central

    Raheem, Mayumi; Leach, Steven T.; Day, Andrew S.; Lemberg, Daniel A.

    2014-01-01

    Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with transforming growth factor-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE. PMID:24910846

  13. Esophageal tissue engineering: A new approach for esophageal replacement

    PubMed Central

    Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

    2012-01-01

    A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly sug- gest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed. PMID:23322987

  14. Spontaneous intramural esophageal dissection: an unusual onset of eosinophilic esophagitis.

    PubMed

    Ibáñez-Sanz, Gemma; Rodríguez Alonso, Lorena; Romero Martínez, Natalia M

    2016-03-01

    A 35-year-old man, with a history of rhinitis, eczema and a dubious achalasia was admitted due to chest pain and sialorrhea. Upper endoscopy showed a little hole and a narrowing of the distal esophagus. A CT-scan with oral contrast exposed a discontinuity of the lumen of the middle third of the esophagus and a dissection of submucosal space 16 cm long. The patient recovered after parenteral nutrition. After four months, an esophageal endoscopic showed transient whitish exudates, longitudinal furrows and esophageal lacerations. The biopsies illustrated significant eosinophilic inflammation, eosinophilic microabscesses and basal cell hyperplasia. PMID:26949147

  15. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential messages. (b) Local Primary (LP) is...

  16. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential messages. (b) Local Primary (LP) is...

  17. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false EAS Designations. 11.18 Section 11.18 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General 11.18 EAS Designations. (a) National Primary (NP) is a source of EAS Presidential messages. (b) Local Primary (LP) is...

  18. Risks of Esophageal Cancer Screening

    MedlinePlus

    ... the type of cells that become malignant (cancerous): Squamous cell carcinoma : Cancer that begins in squamous cells , the thin, ... adenocarcinoma each year and fewer new cases of squamous cell carcinoma. Squamous cell carcinoma of the esophagus is found ...

  19. A Treatment Option for Esophageal Intramural Pseudodiverticulosis.

    PubMed

    Tyberg, Amy; Jodorkovsky, Daniela

    2014-04-01

    Esophageal intramural pseudodiverticulosis (EIPD) is a rare condition often presenting with esophageal strictures. Treatment is often limited to endoscopic dilatation and treatment of the underlying esophageal pathology. We present a case of a patient with longstanding GERD on famotidine (she experienced anaphylaxis with proton pump inhibitors [PPIs]) who presented with dysphagia and weight loss. Work-up revealed a diagnosis of EIPD with a 5-mm mid-esophageal stricture. Therapy with dilatation was unsuccessful until the addition of sucralfate, after which dilatation was successful and symptoms resolved. In patients who are unable to take PPIs, the addition of sucralfate may enhance the success of dilatations of esophageal strictures and EIPD. PMID:26157852

  20. Sloughing Esophagitis: A Not So Common Entity

    PubMed Central

    Akhondi, Hossein

    2014-01-01

    BACKGROUND: Sloughing esophagitis, also known as esophagitis dissecans superficialis, is a very rare and underdiagnosed entity with unknown incidence rate. It can be associated with bullous dermatoses and medications such as central nervous system depressants and those causing esophageal injury. CASE REPORT: A 55-years-old woman was recovering from renal failure due to rhabdomyolysis when she developed dysphagia and odynophagia. Esophagogastroduodenoscopy with biopsy was performed for suspected bullous pemphigus and confirmed sloughing esophagitis. She improved with intravenous steroids. CONCLUSIONS: Sloughing Esophagitis should enter our differential diagnosis more frequently. It is mostly a benign, self-limiting process but when associated with bullous dermatoses will require steroid treatment. PMID:25598761

  1. Ciliated adenocarcinoma of the endometrium.

    PubMed

    Haibach, H; Oxenhandler, R W; Luger, A M

    1985-01-01

    Two cases of ciliated endometrial adenocarcinoma which came to attention in less than one year are described. This entity deserves emphasis, as its ciliation may distract from its histological malignant features. Association of cilia with atypical nuclear features in the same cell is the diagnostic characteristic which distinguishes it from non-ciliated adenocarcinoma overrunning non-malignant ciliated endometrium. The ultrastructural detail of the cilia of malignant cells does not differ from that of non-malignant endometrial glandular epithelium. Our cases raise the question of a possible association of estrogenic effect with ciliated endometrial adenocarcinoma. PMID:4061063

  2. Classification of different patterns of pulmonary adenocarcinomas.

    PubMed

    Truini, Anna; Santos Pereira, Poliana; Cavazza, Alberto; Spagnolo, Paolo; Nosseir, Sofia; Longo, Lucia; Jukna, Agita; Lococo, Filippo; Vincenzi, Giada; Bogina, Giuseppe; Tiseo, Marcello; Rossi, Giulio

    2015-10-01

    The epidemic increase of adenocarcinoma histology accounting for more than 50% of primary lung malignancies and the advent of effective molecular targeted-therapies against specific gene alterations characterizing this tumor type have led to the reconsideration of the pathologic classification of lung cancer. The new 2015 WHO classification provided the basis for a multidisciplinary approach emphasizing the close correlation among clinical, radiologic and molecular characteristics and histopathologic pattern of lung adenocarcinoma. The terms 'bronchioloalveolar carcinoma' and 'mixed adenocarcinoma' have been eliminated, introducing the concepts of 'adenocarcinoma in situ', 'minimally invasive adenocarcinoma' and the use of descriptive predominant patterns in invasive adenocarcinomas (lepidic, acinar, papillary, solid and micropapillary patterns). 'Invasive mucinous adenocarcinoma' is the new definition for mucinous bronchioloalveolar carcinoma, and some variants of invasive adenocarcinoma have been included, namely colloid, enteric and fetal-type adenocarcinomas. A concise update of the immunomorphologic, radiological and molecular characteristics of the different histologic patterns of lung adenocarcinoma is reported here. PMID:26313326

  3. Dietary treatment of eosinophilic esophagitis.

    PubMed

    Gonsalves, Nirmala; Kagalwalla, Amir F

    2014-06-01

    Emerging evidence supports impaired epithelial barrier function as the key initial event in the development of eosinophilic esophagitis (EoE) and other allergic diseases. Symptom resolution, histologic remission, and prevention of both disease and treatment-related complications are the goals of treatment. Successful dietary treatments include elemental, empirical elimination and allergy test directed diets. Dietary therapy with exclusive elemental diet offers the best response. Cow's milk, wheat, egg, soy, peanut/tree nut, and fish/shellfish are the 6 food antigens most likely to induce esophageal inflammation. PMID:24813522

  4. Feeding difficulties in children with esophageal atresia: treatment by a multidisciplinary team.

    PubMed

    Ramsay, M; Birnbaum, R

    2013-01-01

    Esophageal atresia (EA) is one of the congenital neonatal anomalies whose immediate consequence for the newborn is the inability to feed. Most centers strive to minimize the effects of surgeries and subsequent postoperative complications such as esophageal strictures, respiratory problems, and gastrointestinal reflux on the child's ability or motivation to feed. Feeding difficulties in early infancy may not only interrupt maternal expectations of becoming providers of nutrition to their infants but may also influence the infant's development of sensory motor skills and parent-child relationships. Early involvement by a multidisciplinary team consisting of occupational therapist, nutritionist, and psychologist is an important addition to the surgical and medical team. The team assists in preparing mothers for feeding-related difficulties, providing anticipatory guidance to improve feeding abilities and relationships, especially for children with multiple surgical involvements and prolonged periods of non-oral feeding. PMID:23679033

  5. [Nd-YAG laser disobstruction of esophageal endoprostheses occluded by neoplastic development in the palliative treatment of esophageal cancer].

    PubMed

    Tenchini, P; Breda, B; Abrescia, F; Montresor, E; Iacono, C; Angelini, G P; Delaini, G G; Piubello, W

    1986-02-01

    Since August 1984 18 patients suffering from inoperable esophageal cancer have been treated by Nd. Yag Laser therapy under endoscopic control in the Verona University Institute of Clinical Surgery. Three patients, all males ranging in age from 68 to 80 years, had endo-esophageal prostheses which were occluded as a result of the neoplasms. Occlusion of the prostheses had been ascertained by both x-rays and endoscopy. The symptoms consisted of severe dysphagia of solid foods in 2 cases and of solids and liquids in 1 case. The original sites of the tumors were the lower 3rd in two cases and the mid 3rd in 1 case. Histologically, the tumors were identified as 2 squamous-cell carcinomas and 1 adenocarcinoma. Laser treatment was given on average once every 7 days. Patients were admitted to the day hospital, thus avoiding negative repercussions in terms of quality of life or length of hospital stay. In 2 cases there was an improvement in symptoms with the possibility of semi-solid nutrition after a single treatment with 6000-5032 Joules. In the third case, to obtain the same result, 2 treatments were necessary at an interval of 7 days with a total of 9396 J. One patient died of cardiorespiratory failure 24 days after the first treatment. A second patient was treated a further 3 times with a total of 12356 J and is now on a liquid and solid diet 5 months after the first treatment. The third patient was treated 4 times with a total of 15769 J; this patient was on a liquid and solid diet, but died of cardiorespiratory failure 3 months after the first treatment. In the light of our experience, Nd. Yag Laser disocclusion of endo-esophageal prostheses occluded by neoplasms presented no complications and was an appropriate indication in these cases with satisfactory long-term results. PMID:2423261

  6. EA Shuttle Document Retention Effort

    NASA Technical Reports Server (NTRS)

    Wagner, Howard A.

    2010-01-01

    This slide presentation reviews the effort of code EA at Johnson Space Center (JSC) to identify and acquire databases and documents from the space shuttle program that are adjudged important for retention after the retirement of the space shuttle.

  7. Pancreatic adenocarcinoma: epidemiology and genetics.

    PubMed Central

    Flanders, T Y; Foulkes, W D

    1996-01-01

    Pancreatic adenocarcinoma is an important cause of death from cancer throughout the developed world. There are few established environmental risk factors, but a previous history of pancreatitis and exposure to tobacco and salted food appear to be the most important. A family history of pancreatic adenocarcinoma is not common in patients with this disease, but recent research has shown that pancreatic adenocarcinoma can be a feature of cancer susceptibility syndromes associated with germline mutations in p16, BRCA1, BRCA2, and APC. This highlights the need for a full family history in apparently sporadic cases. Somatic mutations in p16, BRCA2, and APC have also been reported in pancreatic cancer; however, K-RAS mutations appear to be the commonest oncogenic alteration. Recent advances in our understanding of the basis of hereditary cancer syndromes may be applicable to the diagnosis, treatment, and possibly prevention of pancreatic adenocarcinoma in the future. PMID:8950667

  8. Adenocarcinoma of the cervical stump

    SciTech Connect

    Goodman, H.M.; Niloff, J.M.; Buttlar, C.A.; Welch, W.R.; Marck, A.; Feuer, E.J.; Lahman, E.A.; Jenison, E.; Knapp, R.C. )

    1989-11-01

    Sixteen women with adenocarcinoma of the cervical stump were treated over a 15-year period. The median survivals of 40 months for stage IB and 17 months for stages II and III were significantly worse compared with those for patients treated for cervical adenocarcinoma of the intact uterus or squamous carcinoma of the cervical stump. The poor results were due to both local and distant failure. Implications regarding tumor radiosensitivity and adjuvant therapy in these high-risk patients are discussed.

  9. Esophageal human beta-defensin expression in eosinophilic esophagitis

    PubMed Central

    Schroeder, Shauna; Robinson, Zachary D.; Masterson, Joanne C.; Hosford, Lindsay; Moore, Wendy; Pan, Zhaoxing; Harris, Rachel; Souza, Rhonda F.; Spechler, Stuart Jon; Fillon, Sophie A.; Furuta, Glenn T.

    2013-01-01

    Background Defensins are antimicrobial peptides expressed on mucosal surfaces that contribute to maintaining intestinal homeostasis by providing innate defense mechanisms for the epithelia. Defensin expression is altered in a number of diseases that affect mucosal surfaces, such as atopic dermatitis, allergic rhinitis, and inflammatory bowel disease. Similar to atopic dermatitis, eosinophilic esophagitis (EoE) is a chronic disease in which the squamous epithelial surface is affected by a similar TH2 microenvironment and eosinophil predominant inflammation. Therefore, we hypothesized defensin expression would be decreased in EoE. Methods To address this, we measured defensin expression in vitro in cell lines derived from patients with EoE (EoE1-T) or gastroesophageal reflux disease (GERD) (NES-G4T cells), and ex vivo in esophageal mucosal biopsy samples from children with EoE, GERD, and control children without esophageal disease. Results IL-5 induced a decrease in human beta-defensin 1 (hBD1) and human beta-defensin 3 (hBD3) expression in EoE1-T but not in NES-G4T cells. Compared to esophageal biopsy specimens from GERD and control children, specimens from EoE pediatric patients revealed significant decrease in mRNA and protein expression for hBD1 and hBD3. Conclusion Diminished expression of hBD1 and hBD3 may make the esophageal epithelium more susceptible to the development and/or perpetuation of EoE. PMID:23385963

  10. Characterization of the autofluorescence of normal and tumoral esophageal epithelium cells

    NASA Astrophysics Data System (ADS)

    Villette, Sandrine; Bourg-Heckly, Genevieve; Pigaglio, Sophie; Validire, Pierre; Grichine, Alexei; Vever-Bizet, Christine

    2003-10-01

    The objectives of this study are to characterize the autofluorescence spectra of normal and tumoral esophageal epithelial cells and to link the cellular spectra with a data basis of in vivo tissular spectra. Our preliminary results show that no difference in spectral distribution can be observed between squamous cell carcinoma, adenocarcinoma and normal cells. A statistical significant difference is observed between the average intensity of the raw spectra of the different cell types. Nucleus autofluorescence presents the same spectral shape as cytoplasm, but with lower intensity.

  11. Analysis of thermal effects in endoscopic nanocarriers-based photodynamic therapy applied to esophageal diseases

    NASA Astrophysics Data System (ADS)

    Salas-García, I.; Fanjul-Vélez, F.; Ortega-Quijano, N.; Wilfert, O.; Hudcova, L.; Poliak, J.; Barcik, P.; Arce-Diego, J. L.

    2014-02-01

    In this work we propose a predictive model that allows the study of thermal effects produced when the optical radiation interacts with an esophageal or stomach disease with gold nanoparticles embedded. The model takes into account light distribution in the tumor tissue by means of a Monte Carlo method. Mie theory is used to obtain the gold nanoparticles optical properties and the thermal model employed is based on the bio-heat equation. The complete model was applied to two types of tumoral tissue (squamous cell carcinoma located in the esophagus and adenocarcinoma in the stomach) in order to study the thermal effects induced by the inclusion of gold nanoparticles.

  12. Eosinophilic esophagitis: trials and tribulations.

    PubMed

    Allen, Katrina J; Heine, Ralf G

    2011-08-01

    Eosinophilic esophagitis (EE) is a recently recognized form of pan-esophagitis, which is characterized by the presence of at least 15 eosinophils per high power field on esophageal histology. EE is closely associated with atopic disorders and occurs predominantly in male patients. Young children are more likely to be sensitized to food allergens whilst aeroallergen sensitization predominates in older children and adults--a pattern reminiscent of the "atopic march". EE presents with a diverse range of gastrointestinal symptoms, including regurgitation, vomiting, feeding difficulties or refusal in infancy, in addition to dysphagia and food bolus impaction in older children and adults. The diagnosis may also be ascertained incidentally in patients undergoing gastroscopy for other suspected gastrointestinal conditions, such as gastroesophageal reflux disease or celiac disease. Complications mainly relate to subepithelial remodeling and fibrosis which may result in dysmotility, dysphagia and esophageal strictures. The proportion of EE patients at risk of these complications is unknown due to a paucity of data on the natural history of EE. There are only few randomized controlled trials assessing the efficacy of treatment modalities for EE, which currently either involve food allergen elimination or use of swallowed aerosolized corticosteroids. This article aims to discuss the complex issues of the diagnosis and long-term management that confront clinicians who care for children with EE. PMID:21415771

  13. Esophageal Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing esophageal cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  14. Pathological characteristics of esophageal cancer

    PubMed Central

    SHI, HONG-YUN; ZHU, SHU-CHAI; SHEN, WEN-BIN; LIU, MIAO-LING

    2014-01-01

    The pathological characteristics of esophageal squamous cell carcinoma, which include regularly occurring multiple carcinogenic lesions (MLs), severe dysplasia (SD) and direct intramural infiltration (DI), were investigated using large pathological sections. A total of 52 esophageal cancer patients underwent surgical resection and were diagnosed with esophageal squamous cell carcinoma. Large sections of the surgical resection specimens were then made for pathological examination. The actual length of the carcinoma was calculated during surgery from the length determined microscopically. ML, SD and DI were identified during pathological examination of the large sections by microscope and were statistically analyzed. The lesion lengths obtained by the various inspection methods differed from each other. ML, SD and DI were identified in 15, 28 and 41 patients, respectively. Furthermore, a higher incidence of DI was observed in patients with lymphatic infiltration or those with a later stage of disease. ML, SD and DI were identified as characteristics of esophageal squamous cell carcinoma, and ML and DI were found to correlate with lymphatic infiltration. PMID:25013466

  15. Efficacy of Intensity Modulated Radiation Therapy After Surgery in Early Stage of Esophageal Carcinoma;

    ClinicalTrials.gov

    2015-12-09

    Esophageal Neoplasm; Esophageal Cancer TNM Staging Primary Tumor (T) T2; Esophageal Cancer TNM Staging Primary Tumor (T) T3; Esophageal Cancer TNM Staging Regional Lymph Nodes (N) N0; Esophageal Cancer TNM Staging Distal Metastasis (M) M0

  16. Obesity and related risk factors in gastric cardia adenocarcinoma.

    PubMed

    Olefson, Sidney; Moss, Steven F

    2015-01-01

    Over recent decades, the incidence of cancers of the gastroesophageal junction, including gastric cardia tumors, has increased markedly. This is a trend that has been well documented, especially in studies from the USA and northern Europe that have also demonstrated a concomitant rise in the ratio of cardia to distal gastric cancers. The rise in the prevalence of gastric cardia adenocarcinoma has been paralleled by the worldwide obesity epidemic, with almost all epidemiological studies reporting increased body mass index and obesity increase the risk of cardia cancer development. However, the strength of this association is less marked than the link between obesity and esophageal adenocarcinoma, and the mechanisms remain poorly understood. Other possible confounders of the relationship between obesity and cardia cancer include the decline in Helicobacter pylori infection and the widespread use of proton pump inhibitors, although these have rarely been controlled for in case-control and cohort studies investigating associations between obesity and cardia cancer. We review these epidemiological trends and discuss proposed mechanisms for the association, drawing attention to controversies over the difficulty of defining cardia cancer. The relative paucity of high-quality epidemiological studies from other regions of the world should prompt further investigation of this issue, especially in populations undergoing rapid socioeconomic change. PMID:25209115

  17. Esophageal atresia and other visceral anomalies in a modified Adriamycin rat model and their correlations with amniotic fluid volume variations.

    PubMed

    França, Willy M G; Gonçalves, Anderson; Moraes, Suzana G; Pereira, Luis A V; Sbragia, Lourenço

    2004-08-01

    The Adriamycin rat model (ARM) has been used to produce visceral malformations in fetuses to explain the mechanisms of foregut division. The models vary in the dosage of Adriamycin (ADR) and in the number of applications. Our study of a modified ARM using 2.2 mg/kg of ADR for 2 days only, intraperitoneally in pregnant rats, is presented. A total of 81 fetuses were obtained with this model from the ADR group, 74 (91%) alive. Uretero-hydronephrosis (UHN) was observed in 70 fetuses (95%), esophageal atresia (EA) in 68 (92%), duodenal atresia (DA) in 68 (92%), bladder hypoplasia (BH) in 67 (90%), plus other malformations. In evaluating amniotic fluid (AF) volume of the fetuses with EA with tracheo-esophageal fistula (TEF) (group I) and EA without TEF (group II), both associated with bilateral UHN when compared with the control group (group III), groups I and II showed higher AF volume in groups I and II than the control group (group III) did ( p=0.0001). In conclusion, ARM was adequate to produce EA and other visceral malformations. The use of ADR in a higher dosage for a shorter period of time produced better results than those presented in previous literature. The increase of AF volume obtained in fetuses presenting EA plus bilateral UHN strongly suggests, despite ureteral dilatation (urinary obstruction), that a malformed communication may exist between the urinary system and the amniotic cavity, permitting the existence of polyhydramnios that is due to digestive obstruction such as EA and DA. PMID:15338172

  18. Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

    SciTech Connect

    Lin, Steven H.; Komaki, Ritsuko; Liao Zhongxing; Wei, Caimiao; Myles, Bevan; Guo Xiaomao; Palmer, Matthew; Mohan, Radhe; Swisher, Stephen G.; Hofstetter, Wayne L.; Ajani, Jaffer A.; Cox, James D.

    2012-07-01

    Purpose: Proton beam therapy (PBT) is a promising modality for the management of thoracic malignancies. We report our preliminary experience of treating esophageal cancer patients with concurrent chemotherapy (CChT) and PBT (CChT/PBT) at MD Anderson Cancer Center. Methods and Materials: This is an analysis of 62 esophageal cancer patients enrolled on a prospective study evaluating normal tissue toxicity from CChT/PBT from 2006 to 2010. Patients were treated with passive scattering PBT with two- or three-field beam arrangement using 180 to 250 MV protons. We used the Kaplan-Meier method to assess time-to-event outcomes and compared the distributions between groups using the log-rank test. Results: The median follow-up time was 20.1 months for survivors. The median age was 68 years (range, 38-86). Most patients were males (82%) who had adenocarcinomas (76%) and Stage II-III disease (84%). The median radiation dose was 50.4 Gy (RBE [relative biologic equivalence]) (range, 36-57.6). The most common grade 2 to 3 acute toxicities from CChT/PBT were esophagitis (46.8%), fatigue (43.6%), nausea (33.9%), anorexia (30.1%), and radiation dermatitis (16.1%). There were two cases of grade 2 and 3 radiation pneumonitis and two cases of grade 5 toxicities. A total of 29 patients (46.8%) received preoperative CChT/PBT, with one postoperative death. The pathologic complete response (pCR) rate for the surgical cohort was 28%, and the pCR and near CR rates (0%-1% residual cells) were 50%. While there were significantly fewer local-regional recurrences in the preoperative group (3/29) than in the definitive CChT/PBT group (16/33) (log-rank test, p = 0.005), there were no differences in distant metastatic (DM)-free interval or overall survival (OS) between the two groups. Conclusions: This is the first report of patients treated with PBT/CChT for esophageal cancer. Our data suggest that this modality is associated with a few severe toxicities, but the pathologic response and clinical outcomes are encouraging. Prospective comparison with more traditional approach is warranted.

  19. Appropriateness of Using Patient-Derived Xenograft Models for Pharmacologic Evaluation of Novel Therapies for Esophageal/Gastro-Esophageal Junction Cancers

    PubMed Central

    Dodbiba, Lorin; Teichman, Jennifer; Fleet, Andrew; Thai, Henry; Starmans, Maud H. W.; Navab, Roya; Chen, Zhuo; Girgis, Hala; Eng, Lawson; Espin-Garcia, Osvaldo; Shen, Xiaowei; Bandarchi, Bizhan; Schwock, Joerg; Tsao, Ming-Sound; El-Zimaity, Hala; Der, Sandy D.; Xu, Wei; Bristow, Robert G.; Darling, Gail E.; Boutros, Paul C.

    2015-01-01

    The high morbidity and mortality of patients with esophageal (E) and gastro-esophageal junction (GEJ) cancers, warrants new pre-clinical models for drug testing. The utility of primary tumor xenografts (PTXGs) as pre-clinical models was assessed. Clinicopathological, immunohistochemical markers (p53, p16, Ki-67, Her-2/neu and EGFR), and global mRNA abundance profiles were evaluated to determine selection biases of samples implanted or engrafted, compared with the underlying population. Nine primary E/GEJ adenocarcinoma xenograft lines were further characterized for the spectrum and stability of gene/protein expression over passages. Seven primary esophageal adenocarcinoma xenograft lines were treated with individual or combination chemotherapy. Tumors that were implanted (n=55) in NOD/SCID mice had features suggestive of more aggressive biology than tumors that were never implanted (n=32). Of those implanted, 21/55 engrafted; engraftment was associated with poorly differentiated tumors (p=0.04) and older patients (p=0.01). Expression of immunohistochemical markers were similar between patient sample and corresponding xenograft. mRNA differences observed between patient tumors and first passage xenografts were largely due to loss of human stroma in xenografts. mRNA patterns of early vs late passage xenografts and of small vs large tumors of the same passage were similar. Complete resistance was present in 2/7 xenografts while the remaining tumors showed varying degrees of sensitivity, that remained constant across passages. Because of their ability to recapitulate primary tumor characteristics during engraftment and across serial passaging, PTXGs can be useful clinical systems for assessment of drug sensitivity of human E/GEJ cancers. PMID:25826681

  20. Role of Proton Pump Inhibitor on Esophageal Carcinogenesis and Pancreatic Acinar Cell Metaplasia Development: An Experimental In Vivo Study

    PubMed Central

    Dall’Olmo, Luigi; Fassan, Matteo; Dassie, Elisa; Scarpa, Marco; Realdon, Stefano; Cavallin, Francesco; Cagol, Matteo; Battaglia, Giorgio; Pizzi, Marco; Guzzardo, Vincenza; Franceschinis, Erica; Pasut, Gianfranco; Rugge, Massimo; Zaninotto, Giovanni; Realdon, Nicola; Castoro, Carlo

    2014-01-01

    Chronic gastro-duodenal reflux in the esophagus is a major risk for intestinal metaplasia and Barrett’s adenocarcinoma. A role for chronic use of proton pump inhibitor (PPI) in the increased incidence of esophageal adenocarcinoma in Western countries has been previously suggested. The aim of this work was to study the effect of chronic administration of omeprazole (a proton pump inhibitor) per os in a model of reflux induced esophageal carcinogenesis. One week after esophago-gastro-jejunostomy, 115 Sprague-Dawley rats were randomized to receive 10 mg/Kg per day of omeprazole or placebo, 5 days per week. The esophago-gastric specimens were collected 28±2 weeks after randomization and analyzed in a blinded fashion. Mortality and esophageal metaplasia rates did not differ between the two groups (p = 0.99 for mortality, p = 0.36 for intestinal metaplasia and p = 0.66 for multi-layered epithelium). Gastric pancreatic acinar cell metaplasia (PACM) was more frequently observed in PPI-treated rats (p = 0.003). Severe ulcer lesions significantly prevailed in the placebo group (p = 0.03). Locally invasive esophageal epithelial neoplasia were observed in 23/39 PPI-treated versus 14/42 placebo-animals (p = 0.03). In conclusion, chronic omeprazole treatment improved the healing of esophageal ulcerative lesions. Locally invasive neoplastic lesions and PACM prevailed among PPI-treated animals. However, neither an effect on the overall mortality nor on the incidence of pre-neoplastic lesions was observed in this work. PMID:25415190

  1. Structural and numerical changes of chromosome X in patients with esophageal atresia

    PubMed Central

    Brosens, Erwin; de Jong, Elisabeth M; Barakat, Tahsin Stefan; Eussen, Bert H; D'haene, Barbara; De Baere, Elfride; Verdin, Hannah; Poddighe, Pino J; Galjaard, Robert-Jan; Gribnau, Joost; Brooks, Alice S; Tibboel, Dick; de Klein, Annelies

    2014-01-01

    Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a relatively common birth defect often associated with additional congenital anomalies such as vertebral, anal, cardiovascular, renal and limb defects, the so-called VACTERL association. Yet, little is known about the causal genetic factors. Rare case reports of gastrointestinal anomalies in children with triple X syndrome prompted us to survey the incidence of structural and numerical changes of chromosome X in patients with EA/TEF. All available (n=269) karyotypes of our large (321) EA/TEF patient cohort were evaluated for X-chromosome anomalies. If sufficient DNA material was available, we determined genome-wide copy number profiles with SNP array and identified subtelomeric aberrations on the difficult to profile PAR1 region using telomere-multiplex ligation-dependent probe amplification. In addition, we investigated X-chromosome inactivation (XCI) patterns and mode of inheritance of detected aberrations in selected patients. Three EA/TEF patients had an additional maternally inherited X chromosome. These three female patients had normal random XCI patterns. Two male EA/TEF patients had small inherited duplications of the XY-linked SHOX (Short stature HOmeoboX-containing) locus. Patients were small for gestational age at birth (EA/TEF and no duplications of the SHOX gene were reported so far in these patients. As normal patterns of XCI were seen, overexpression of X-linked genes that escape XCI, such as the SHOX gene, could be pathogenic by disturbing developmental pathways. PMID:24398799

  2. Reduction of E-cadherin by human defensin-5 in esophageal squamous cells.

    PubMed

    Nomura, Yoshiki; Tanabe, Hiroki; Moriichi, Kentaro; Igawa, Satomi; Ando, Katsuyoshi; Ueno, Nobuhiro; Kashima, Shin; Tominaga, Motoya; Goto, Takuma; Inaba, Yuhei; Ito, Takahiro; Ishida-Yamamoto, Akemi; Fujiya, Mikihiro; Kohgo, Yutaka

    2013-09-13

    Barrett's esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barrett's carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE. PMID:23958301

  3. Cytoskeletal changes induced by allosteric modulators of calcium-sensing receptor in esophageal epithelial cells

    PubMed Central

    Abdulnour-Nakhoul, Solange; Brown, Karen L; Rabon, Edd C; Al-Tawil, Youhanna; Islam, Mohammed T; Schmieg, John J; Nakhoul, Nazih L

    2015-01-01

    The calcium-sensing receptor (CaSR), a G-protein-coupled receptor, plays a role in glandular and fluid secretion in the gastrointestinal tract, and regulates differentiation and proliferation of epithelial cells. We examined the expression of CaSR in normal and pathological conditions of human esophagus and investigated the effect of a CaSR agonist, cinacalcet (CCT), and antagonist, calhex (CHX), on cell growth and cell–cell junctional proteins in primary cultures of porcine stratified squamous esophageal epithelium. We used immunohistochemistry and Western analysis to monitor expression of CaSR and cell–cell adhesion molecules, and MTT assay to monitor cell proliferation in cultured esophageal cells. CCT treatment significantly reduced proliferation, changed the cell shape from polygonal to spindle-like, and caused redistribution of E-cadherin and β-catenin from the cell membrane to the cytoplasm. Furthermore, it reduced expression of β-catenin by 35% (P < 0.02) and increased expression of a proteolysis cleavage fragment of E-cadherin, Ecad/CFT2, by 2.3 folds (P < 0.01). On the other hand, CHX treatment enhanced cell proliferation by 27% (P < 0.01), increased the expression of p120-catenin by 24% (P < 0.04), and of Rho, a GTPase involved in cytoskeleton remodeling, by 18% (P < 0.03). In conclusion, CaSR is expressed in normal esophagus as well as in Barrett’s, esophageal adenocarcinoma, squamous cell carcinoma, and eosinophilic esophagitis. Long-term activation of CaSR with CCT disrupted the cadherin–catenin complex, induced cytoskeletal remodeling, actin fiber formation, and redistribution of CaSR to the nuclear area. These changes indicate a significant and complex role of CaSR in epithelial remodeling and barrier function of esophageal cells. PMID:26603452

  4. Cytoskeletal changes induced by allosteric modulators of calcium-sensing receptor in esophageal epithelial cells.

    PubMed

    Abdulnour-Nakhoul, Solange; Brown, Karen L; Rabon, Edd C; Al-Tawil, Youhanna; Islam, Mohammed T; Schmieg, John J; Nakhoul, Nazih L

    2015-11-01

    The calcium-sensing receptor (CaSR), a G-protein-coupled receptor, plays a role in glandular and fluid secretion in the gastrointestinal tract, and regulates differentiation and proliferation of epithelial cells. We examined the expression of CaSR in normal and pathological conditions of human esophagus and investigated the effect of a CaSR agonist, cinacalcet (CCT), and antagonist, calhex (CHX), on cell growth and cell-cell junctional proteins in primary cultures of porcine stratified squamous esophageal epithelium. We used immunohistochemistry and Western analysis to monitor expression of CaSR and cell-cell adhesion molecules, and MTT assay to monitor cell proliferation in cultured esophageal cells. CCT treatment significantly reduced proliferation, changed the cell shape from polygonal to spindle-like, and caused redistribution of E-cadherin and β-catenin from the cell membrane to the cytoplasm. Furthermore, it reduced expression of β-catenin by 35% (P < 0.02) and increased expression of a proteolysis cleavage fragment of E-cadherin, Ecad/CFT2, by 2.3 folds (P < 0.01). On the other hand, CHX treatment enhanced cell proliferation by 27% (P < 0.01), increased the expression of p120-catenin by 24% (P < 0.04), and of Rho, a GTPase involved in cytoskeleton remodeling, by 18% (P < 0.03). In conclusion, CaSR is expressed in normal esophagus as well as in Barrett's, esophageal adenocarcinoma, squamous cell carcinoma, and eosinophilic esophagitis. Long-term activation of CaSR with CCT disrupted the cadherin-catenin complex, induced cytoskeletal remodeling, actin fiber formation, and redistribution of CaSR to the nuclear area. These changes indicate a significant and complex role of CaSR in epithelial remodeling and barrier function of esophageal cells. PMID:26603452

  5. Eosinophilic esophagitis: an immune-mediated esophageal disease.

    PubMed

    Weinbrand-Goichberg, Jenny; Segal, Idit; Ovadia, Adi; Levine, Arie; Dalal, Ilan

    2013-07-01

    Eosinophilic esophagitis (EoE) is an emerging disease defined by esophageal dysfunction, by typical endoscopic findings and by abnormal eosinophilic inflammation within the esophagus. Eosinophilic accumulation in the esophagus occurs as a result of esophageal overexpression of pro-inflammatory mediators, including T cells and mast cells, cytokines such as interleukin (IL)-13, IL-5 and IL-15, as well as chemoattractants (eotaxin and transforming growth factor-β1, fibroblast growth factor and the newly characterized gene--thymic stromal lymphopoietin, which is a key regulator of allergic sensitization initiation). The role of allergy, particularly food allergy in EoE is indisputable, as elimination diet is a proven commonly used treatment for the disease. However, unlike classical immediate IgE-mediated reaction to allergen, EoE is associated with an altered immune response, characterized by a combination of IgE-mediated and non-IgE-mediated mechanisms. In this review, we aim to discuss the many typical aspects of EoE as opposed to other entities involving the esophagus, with focusing on the aberrant immune-mediated key players contributing to the pathogenesis of this unique disease. PMID:23579771

  6. Esophageal motility abnormalities in gastroesophageal reflux disease.

    PubMed

    Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

    2014-05-01

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted. PMID:24868489

  7. Esophageal Stenosis Associated With Tumor Regression in Radiotherapy for Esophageal Cancer: Frequency and Prediction

    SciTech Connect

    Atsumi, Kazushige; Shioyama, Yoshiyuki; Arimura, Hidetaka; Terashima, Kotaro; Matsuki, Takaomi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji; Nakamura, Katsumasa; Honda, Hiroshi

    2012-04-01

    Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.

  8. Pradaxa-induced esophageal ulcer.

    PubMed

    Wood, Michele; Shaw, Paul

    2015-01-01

    Pradaxa (dabigatran) is a direct thrombin inhibitor approved for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. We describe a case of esophageal ulceration associated with Pradaxa administration in a 75-year-old man. The patient reported difficulty swallowing and a burning sensation after taking his first dose of Pradaxa. An esophagogastroduodenoscopy (EGD) revealed linear ulcerations in the mid-esophagus. Pradaxa was held beginning the day before the EGD. The patient reported that his pain and difficulty swallowing resolved on stopping Pradaxa. Pradaxa is formulated with a tartaric acid excipient to reduce variability in absorption. We hypothesise that the capsule lodged in the patient's esophagus and the tartaric acid may have caused local damage resulting in an esophageal ulcer. It is important to educate patients on proper administration of Pradaxa, to decrease the risk of this rare, but potentially serious adverse event. PMID:26452739

  9. Allergic Mechanisms in Eosinophilic Esophagitis

    PubMed Central

    Wechsler, Joshua B; Bryce, Paul J

    2014-01-01

    Paralleling the overall trend in allergic diseases, Eosinophilic Esophagitis is rapidly increasing in incidence. It is associated with food antigen-triggered, eosinophil-predominant inflammation and the pathogenic mechanisms have many similarities to other chronic atopic diseases, such as eczema and allergic asthma. Studies in animal models and from patients over the last 15 years have suggested that allergic sensitization leads to food-specific IgE and T-helper lymphocyte type 2 cells, both of which appear to contribute to the pathogenesis along with basophils, mast cells, and antigen-presenting cells. This review will outline our current understandings of the allergic mechanisms that drive eosinophilic esophagitis, drawing from clinical and translational studies in humans as well as experimental animal models. PMID:24813516

  10. [Surgical treatment of esophageal diverticula].

    PubMed

    Constantinoiu, S; Constantin, A; Predescu, D; Mates, I N; Mocanu, A; Gheorghe, M; Hoară, P; Achim, F; Cociu, L

    2011-01-01

    The aim of this paper is to evaluate the methods and therapeutic principles of esophageal diverticula pathology. We analyze the main pathological mechanisms which establish the therapeutic attitude linked with a complex pretherapeutic evaluation. In our study we enrolled 12 patients operated between 2001-2009 for esophageal diverticula with different topography. In this period of time there were much more patients diagnosed with this pathology, but the need for surgery was establish very tight regarding the actual practical guide which impose the identification and interception of physiological mechanisms by the surgical procedure. We highlight the particular technical details, as well as the important differences of postoperatory complications according to the topography of the diverticula pouch. PMID:21523958

  11. Eosinophilic Esophagitis: A Comprehensive Review.

    PubMed

    Cianferoni, Antonella; Spergel, Jonathan

    2016-04-01

    Eosinophilic esophagitis (EoE) is an emerging chronic atopic clinical-pathologic disease with an estimated prevalence of 1/1000 similar to the one of Crohn's diseases. Usually, EoE is firstly suspected due to symptoms that are caused by esophageal dysfunction and/or fibrosis. EoE diagnosis is confirmed if the esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf) as a peak value in one or more of at least four specimens obtained randomly from the esophagus. Most of the patients affected by EoE have other atopic diseases such as allergic rhinitis, asthma, IgE-mediated food allergies, and/or atopic dermatitis. The local inflammation is a T helper type 2 (Th2) flogosis, which most likely is driven by a mixed IgE and non-IgE-mediated reaction to food and/or environmental allergens. Recently published genetic studies showed also that EoE is associated with single nucleotide polymorphism (SNP) on genes which are important in atopic inflammation such as thymic stromal lymphopoietin (TSLP) located close to the Th2 cytokine cluster (IL-4, IL-5, IL-13) on chromosome 5q22. When the EoE diagnosis is made, it is imperative to control the local eosinophilic inflammation not only to give symptomatic relief to the patient but also to prevent complications such as esophageal stricture and food impaction. EoE is treated like many other atopic diseases with a combination of topical steroids and/or food antigen avoidance. PMID:26194940

  12. True Intramural Esophageal Duplication Cyst.

    PubMed

    Al-Riyami, Salim; Al-Sawafi, Yaqoob

    2015-11-01

    Esophageal duplication is the second most common site of gastrointestinal duplication and most cases present with complications. These complications include bleeding, infection, dysphagia, and dyspnea. We report an incidental case of a true intramural esophageal duplication cyst in a new military recruit. The patient was diagnosed in Armed Forces Hospital, Oman. The patient came for a pre-recruitment routine check-up, he was found to have a suspicious soft tissue lesion on chest X-ray. He was referred to the thoracic surgeon for further investigations. The investigations included computed tomography and magnetic resonance imaging chest scans, barium swallow, endoscopy and, finally, an endoscopic ultrasound. All workup pointed to a diagnosis of esophageal duplication cyst; therefore, the decision was made to excise the lesion after discussion with the patient about the possible diagnosis and nature of the treatment. The cyst was completely excised thoracoscopically with uneventful recovery. The patient was discharged a few days later and was doing well in subsequent visits to the outpatient department. The histopathological exam confirmed the diagnosis of a true congenital duplication cyst, which was lined by pseudostrati?ed ciliated columnar epithelium overlying double layers of thick bundles of smooth muscle ?bers. PMID:26674014

  13. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... logging. For received alert messages formatted in both the EAS Protocol and Common Alerting Protocol, a... means to permit the selective display and logging of EAS messages containing header codes for state and... display and logging capability for EAS messages containing header codes for state and local events....

  14. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... logging. For received alert messages formatted in both the EAS Protocol and Common Alerting Protocol, a... means to permit the selective display and logging of EAS messages containing header codes for state and... display and logging capability for EAS messages containing header codes for state and local events....

  15. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described... messages and one for data messages (RS-232C with standard protocol and 1200 baud rate). (3) Outputs. The encoder shall have two outputs, one audio port and one data port (RS-232C with standard protocol and...

  16. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described... messages and one for data messages (RS-232C with standard protocol and 1200 baud rate). (3) Outputs. The encoder shall have two outputs, one audio port and one data port (RS-232C with standard protocol and...

  17. Clinical Application of Esophageal High-resolution Manometry in the Diagnosis of Esophageal Motility Disorders

    PubMed Central

    van Hoeij, Froukje B; Bredenoord, Albert J

    2016-01-01

    Esophageal high-resolution manometry (HRM) is replacing conventional manometry in the clinical evaluation of patients with esophageal symptoms, especially dysphagia. The introduction of HRM gave rise to new objective metrics and recognizable patterns of esophageal motor function, requiring a new classification scheme: the Chicago classification. HRM measurements are more detailed and more easily performed compared to conventional manometry. The visual presentation of acquired data improved the analysis and interpretation of esophageal motor function. This led to a more sensitive, accurate, and objective analysis of esophageal motility. In this review we discuss how HRM changed the way we define and categorize esophageal motility disorders. Moreover, we discuss the clinical applications of HRM for each esophageal motility disorder separately. PMID:26631942

  18. Clinical Application of Esophageal High-resolution Manometry in the Diagnosis of Esophageal Motility Disorders.

    PubMed

    van Hoeij, Froukje B; Bredenoord, Albert J

    2016-01-31

    Esophageal high-resolution manometry (HRM) is replacing conventional manometry in the clinical evaluation of patients with esophageal symptoms, especially dysphagia. The introduction of HRM gave rise to new objective metrics and recognizable patterns of esophageal motor function, requiring a new classification scheme: the Chicago classification. HRM measurements are more detailed and more easily performed compared to conventional manometry. The visual presentation of acquired data improved the analysis and interpretation of esophageal motor function. This led to a more sensitive, accurate, and objective analysis of esophageal motility. In this review we discuss how HRM changed the way we define and categorize esophageal motility disorders. Moreover, we discuss the clinical applications of HRM for each esophageal motility disorder separately. PMID:26631942

  19. De novo gastric adenocarcinoma 1 year after sleeve gastrectomy in a transplant patient

    PubMed Central

    Masrur, M.; Elli, E.; Gonzalez-Ciccarelli, L.F.; Giulianotti, P.C.

    2016-01-01

    Introduction It has been reported in the literature that upper gastrointestinal malignancies after bariatric surgery are mostly gastro-esophageal, although it is not clear whether bariatric surgery represents a risk factor for the development of esophageal and/or gastric cancer. We report a case of a de novo gastric adenocarcinoma occurring in a transplant patient 1 year after a laparoscopic sleeve gastrectomy. Presentation of case A 44 year-old woman with a BMI of 38 kg/m2, hypertension, type 1 diabetes mellitus, multiple malignancies and a pancreas transplant underwent laparoscopic sleeve gastrectomy. The patient presented with intense dysphagias during the follow up. Studies were performed and the diagnoses of grade 2/3 adenocarcinoma were made. The patient underwent a robotic assisted total gastrectomy with a roux-en-y intracorporeal esophagojejunostomy. The procedure resulted in multiple metastasic lymph nodes, focal and transmural invasions to multiple organs with a tumor free margin resection. The patient presented with a postoperative pleural effusion, with no further complications. Discussion The diagnosis of gastroesophageal cancer after bariatric surgery is usually late since these patients have common upper gastrointestinal symptoms related to the procedure that could delay the diagnosis. De novo gastric cancer after sleeve gastrectomy has only been reported in one instance, in contrast with other bariatric surgery procedures. Conclusions No direct relation has been established between sleeve gastrectomy and the development of gastric cancer. Robotic procedures allow for complex multiorgan resections, while preserving the benefits of minimally invasive surgery. PMID:26774417

  20. Telomere maintenance in laser capture microdissection-purified Barrett's adenocarcinoma cells and effect of telomerase inhibition in vivo

    PubMed Central

    Shammas, Masood A; Qazi, Aamer; Batchu, Ramesh B; Bertheau, Robert C; Wong, Jason YY; Rao, Manjula Y; Prasad, Madhu; Chanda, Diptiman; Ponnazhagan, Selvarangan; Anderson, Kenneth C; Steffes, Christopher P; Munshi, Nikhil C; De Vivo, Immaculata; Beer, David G.; Gryaznov, Sergei; Weaver, Donald W; Goyal, Raj K

    2009-01-01

    Purpose: The aims of this study were to investigate telomere function in normal and Barrett's esophageal adenocarcinoma (BEAC) cells purified by laser capture microdissection (LCM) and to evaluate the impact of telomerase inhibition in cancer cells in vitro and in vivo. Experimental Design: Epithelial cells were purified from surgically resected esophagi. Telomerase activity was measured by modified Telomeric Repeat Amplification Protocol and telomere length determined by Real-Time PCR assay. To evaluate the impact of telomerase inhibition, adenocarcinoma cell lines were continuously treated with a specific telomerase inhibitor (GRN163L) and live cell number determined weekly. Apoptosis was evaluated by annexin labeling and senescence by beta-galactosidase staining. For in vivo studies, SCID-mice were subcutaneously inoculated with adenocarcinoma cells and following appearance of palpable tumors, injected intraperitoneally with saline or GRN163L. Results: Telomerase activity was significantly elevated whereas telomeres were shorter in BEAC cells relative to normal esophageal epithelial cells. The treatment of adenocarcinoma cells with telomerase inhibitor, GRN163L, led to loss of telomerase activity, reduction in telomere length, and growth arrest through induction of both the senescence and apoptosis. GRN163L induced cell death could also be expedited by addition of chemotherapeutic agents, doxorubicin and ritonavir. Finally, the treatment with GRN163L led to a significant reduction in tumor volume in a subcutaneous tumor model. Conclusions: We show that telomerase activity is significantly elevated whereas telomeres are shorter in BEAC and suppression of telomerase inhibits proliferation of adenocarcinoma cells both in vitro and in vivo. PMID:18676772

  1. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Esophageal stethoscope. 868.1910 Section 868.1910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1910 Esophageal stethoscope....

  2. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Esophageal stethoscope. 868.1910 Section 868.1910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1910 Esophageal stethoscope....

  3. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Esophageal stethoscope. 868.1910 Section 868.1910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1910 Esophageal stethoscope....

  4. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Esophageal stethoscope. 868.1910 Section 868.1910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1910 Esophageal stethoscope....

  5. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal stethoscope. 868.1910 Section 868.1910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1910 Esophageal stethoscope....

  6. Energy spectrum of muon in EAS

    NASA Astrophysics Data System (ADS)

    Matsumoto, H.; Iyono, A.; Noda, C.; Masuda, M.; Yamamoto, I.; Wada, T.; Okei, K.; Tsuji, S.; Morita, T.; Okita, M.; Takahashi, N.; Liang, S.; Yamashita, Y.; Nakatsuka, T.; Ochi, N.

    2008-01-01

    The compact extensive air shower (EAS) array which consists of 8 scintillation counters, and the solid iron magnet spectrometer (the Okayama muon telescope) have been used to measure energy spectrum of muons in EAS from January 2004 in Okayama University. We compared the result of the muon energy spectrum tagged by EAS trigger signals with EAS simulations which agreed with higher energy hadronic interaction models such as QGSJET and SYBILL, and lower energy hadronic ones such as Hillas Splitting Algorithm, GHEISHA and UrQMD, in order to verify the influence of the hadronic interaction model upon properties of EAS particles, especially the energy spectrum of muons.

  7. Esophageal carcinoma with doubtful extirpability. Value of preoperative chemotherapy plus radiotherapy.

    PubMed

    Sielezneff, I; Thomas, P; Giovannini, M; Guidicelli, R; Seitz, J F; Fuentes, P

    1993-01-01

    To improve resectability for bulky esophageal tumors and/or tumors evolving close to the pharyngo-esophageal junction (PEJ), a combined preoperative chemotherapy plus radiotherapy (CT+RT) was given in 25 patients. There were 23 men and 2 women (mean age: 55 years); 21 had squamous cell carcinoma and 4 had adenocarcinoma. According to TNM classification based on computed tomography, the tumor was graded T3 in 20 cases, T4 in 2, T2 in 2 and T1 in 1. The preoperative treatment included two sessions of continuous infusion of 5-fluorouracil (800 mg/m2 per day) and cisplatin (20 mg/m2 per day), and combined radiotherapy (3 Gy/day). The overall tolerance was acceptable. The tumoral mass decreased in 23 patients (92%). All the patients underwent a wide esophagectomy; among the six patients with a tumor close to the PEJ, two required an associated pharyngolaryngectomy. The operative mortality rate was 8%. Major non-fatal complications occurred in 52%. On histology, there was no evidence of residual disease in seven patients (28%). The median survival was 18 months and the overall survival rate was 22.1% at 2 years. For the patients who had a complete histological response, the 2-year survival rate was 35%. Our data suggest that combined CT+RT may improve resectability of esophageal carcinoma. Improved survival rates seem to be appreciable in patients with a complete histologic response. PMID:8297615

  8. [Endoscopic methods of gastro-esophageal reflux disease (GERD) treatment and their complications].

    PubMed

    Gil, Jerzy; Błaszak, Antoni; Wojtuń, Stanisław; Wojtkowiak, Marek

    2007-05-01

    Tretament in gastro-esophageal reflux disease (GERD) is in constant change. It is caused by the fact of change and development of diagnostic and therapeutic methods. Alternative methods of treatment are still searched beacause patients do not accept many years long drug treatment or surgical procedures. New methods are developed. Some of them as endoscopic fundoplication or methods of polimerizing substances injection in the area of lower esophageal sphincer have been abandoned because of low quickly diminishing efficacy Endoscopic sewing that implicate all layers of gaster is still under clinical trials and is considered as interesting. Stertt's procedure that is based on electromagnetic wave application in the area of lower esophageal sphincter is used in clinical practice. Despite effective methods of diagnosing and treatment of GERD there is no evidence of lowering incidence of complications of GERD. It is still common to find esophagus stricture as the first illness manifastation. Chronic character of GERD is associated with intestinal metaplasia and adenocarcinoma of the esophagus in its distal part. The most effective endoscopic methods of the treatment include: endoscopic dilation of the strictures and endoscopic methods of patological epithelium removal in Barrett's esophagus. These are: photodynamic therapy, argon coagulation, laser thermoablation, multipolar ablation and endoscpic mucosectomy. The paper is the review of the methods aimed at GERD and its complication treatment. PMID:17679388

  9. Epidemiological studies of esophageal cancer in the era of genome-wide association studies

    PubMed Central

    Wang, An-Hui; Liu, Yuan; Wang, Bo; He, Yi-Xuan; Fang, Ye-Xian; Yan, Yong-Ping

    2014-01-01

    Esophageal cancer (EC) caused about 395000 deaths in 2010. China has the most cases of EC and EC is the fourth leading cause of cancer death in China. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type (90%-95%), while the incidence of esophageal adenocarcinoma (EAC) remains extremely low in China. Traditional epidemiological studies have revealed that environmental carcinogens are risk factors for EC. Molecular epidemiological studies revealed that susceptibility to EC is influenced by both environmental and genetic risk factors. Of all the risk factors for EC, some are associated with the risk of ESCC and others with the risk of EAC. However, the details and mechanisms of risk factors involved in the process for EC are unclear. The advanced methods and techniques used in human genome studies bring a great opportunity for researchers to explore and identify the details of those risk factors or susceptibility genes involved in the process of EC. Human genome epidemiology is a new branch of epidemiology, which leads the epidemiology study from the molecular epidemiology era to the era of genome wide association studies (GWAS). Here we review the epidemiological studies of EC (especially ESCC) in the era of GWAS, and provide an overview of the general risk factors and those genomic variants (genes, SNPs, miRNAs, proteins) involved in the process of ESCC. PMID:25133033

  10. Reduction to homozygosity involving p53 in esophageal cancers demonstrated by the polymerase chain reaction.

    PubMed Central

    Meltzer, S J; Yin, J; Huang, Y; McDaniel, T K; Newkirk, C; Iseri, O; Vogelstein, B; Resau, J H

    1991-01-01

    Loss of heterozygosity affecting chromosome 17p has been detected at high frequencies in a variety of human tumors, including cancers of the colon, breast, lung, and brain. One presumed target of these losses is p53, a tumor suppressor gene located on 17p. To our knowledge, loss of heterozygosity has not yet been reported at any locus, including p53, in human esophageal cancer. Moreover, current methods of detecting loss of heterozygosity depend on the availability of large amounts of high molecular weight DNA, making the study of small biopsy specimens or paraffin-embedded tissues problematic. We examined 52 primary human esophageal neoplasms for loss of heterozygosity affecting the p53 gene by using the polymerase chain reaction. Loss of one allele was detected in 52% of informative cases and was more common in squamous carcinomas than in adenocarcinomas. Southern blot analysis was used to confirm polymerase chain reaction-derived data. The identification of allelic loss in approximately half of the tumors analyzed supports the hypothesis that inactivation of p53 is involved in the pathogenesis of esophageal cancer. Images PMID:2052580

  11. Foker Technique for the Management of Pure Esophageal Atresia: Long-Term Outcomes at a Single Institution.

    PubMed

    Bobanga, Iuliana Dit; Barksdale, Edward Metz

    2016-04-01

    Introduction We present the short- and long-term outcomes in the management of pure long-gap esophageal atresia (LGEA) using the Foker technique (FT) of esophageal elongation by external axial traction at a single institution. Methods All patients undergoing esophageal atresia (EA) repair with FT over a 10-year period were included in the study. Demographic data, birth weight, gestational age, associated anomalies, management, and short- and long-term outcomes were studied. Results Five patients (three males) were treated with FT in the study period, all with LGEA, with a mean birth weight of 1,926 g (range, 541-2,890 g). Four infants had associated anomalies. Primary repair after FT axial traction was achieved in four patients after a mean traction time of 13 days (range, 12-15 days). FT failed in one patient who had esophageal perforation from traumatic orogastric tube placement at birth and extensive matting of the esophagus at the time of FT attempt. The mean age at definitive esophageal anastomosis was 11.5 weeks (range, 8-14 weeks). In three of the five patients, traction sutures from the distal esophageal segment tore away, requiring a thoracotomy for replacement. One of the four patients had a confined leak at the anastomosis. All four patients developed strictures at the anastomosis, requiring serial dilations (mean 12 dilations, range 6-21 dilations), and three of those patients underwent a thoracotomy for stricture resection (two patients) or stricturoplasty (one patient). On long-term follow-up, all patients in whom a primary anastomosis was achieved had their gastrostomy closed and were on full oral feeds. Conclusion FT was successful in achieving a primary anastomosis in 80% of the patients with LGEA, with a significant morbidity but favorable long-term outcomes. PMID:25774957

  12. Lichenoid esophagitis: clinicopathologic overlap with established esophageal lichen planus.

    PubMed

    Salaria, Safia N; Abu Alfa, Amer K; Cruise, Michael W; Wood, Laura D; Montgomery, Elizabeth A

    2013-12-01

    Lichen planus (LP) affects mucocutaneous surfaces and is characterized by intraepithelial and lamina propria lymphocytosis and squamous cell apoptosis (Civatte bodies). Lichen planus esophagitis (LPE) is underrecognized; concurrent cutaneous disease is present in some patients, but LPE alone is more common. We diagnose patients with characteristic pathologic findings of LPE and known correlation with skin disease or immunofluorescence (IF) results as LPE but use descriptive terminology ("lichenoid esophagitis pattern" [LEP]) when confirmation is unavailable. We reviewed clinicopathologic features of patients diagnosed at our institution with LPE or LEP. There were 88 specimens with LPE or LEP from 65 patients. Most patients were female. Seventeen patients had LPE confirmed by IF. Five patients had both esophageal (1 with IF) and skin LP. Strictures were a prominent presenting feature in LPE patients, with disease distribution more frequent in the upper and lower esophagus. Dysphagia was a common reason for endoscopy in LEP patients. Rheumatologic diseases are more common in patients with LPE compared with LEP. Viral hepatitides and human immunodeficiency virus (HIV) infections are associated with LEP. We defined polypharmacy as patients taking >3 medications; this finding was present in both LPE and LEP cohorts; however, this is a prominent feature in those with established LPE. Progression to dysplasia was noted in both cohorts. About 5% of LPE patients have tandem skin manifestations. LPE is more likely than LEP to arise in women, result in stricture formation, and be associated with rheumatologic disorders and polypharmacy, whereas LEP is associated with viral hepatitis and HIV. Both can progress to neoplasia. As the risk of stricture formation is high in patients with LPE, it is worth performing pertinent IF studies to confirm LPE, although knowledge of the clinical association of LEP with viral hepatitis, HIV, and use of multiple medications is of value in daily practice. PMID:24061525

  13. Posttraumatic Stress Reactions in Parents of Children Esophageal Atresia

    PubMed Central

    Le Gouëz, Morgane; Alvarez, Luis; Rousseau, Véronique; Hubert, Philippe; Abadie, Véronique; Lapillonne, Alexandre; Kermorvant-Duchemin, Elsa

    2016-01-01

    Objective The aim of this study was to investigate psychological stress in parents of children with esophageal atresia and to explore factors associated with the development of Posttraumatic Stress disorder (PTSD). Design Self-report questionnaires were administered to parents of children with EA. Domains included: (1) sociodemographic data, current personal difficulties, assessment scales for the quality of life and for the global health status of the child (2) French-validated versions of the Perinatal Posttraumatic Stress disorder Questionnaire and of the State-Trait Anxiety Inventory. Associations between PTSD and severity of the neonatal course, presence of severe sequelae at 2 years of age, and quality of life and global health status of children according to their parents’ perception were studied. Setting A Tertiary care University Hospital Results Among 64 eligible families, 54 parents of 38 children (59%) participated to the study. PTSD was present in 32 (59%) parents; mothers were more frequently affected than fathers (69 vs 46%, p = 0.03). Four mothers (8%) had severe anxiety. PTSD was neither associated with neonatal severity nor with severe sequelae at 2 years. Parents with PTSD rated their child’s quality of life and global health status significantly lower (7.5 vs 8.6; p = 0.01 and 7.4 vs 8.3; p = 0.02 respectively). Conclusions PTSD is frequent in parents of children with esophageal atresia, independently of neonatal severity and presence of severe sequelae at 2 years of age. Our results highlight the need for a long-term psychological support of families. PMID:26953589

  14. Association of esophageal candidiasis and squamous cell carcinoma

    PubMed Central

    Delsing, C.E.; Bleeker-Rovers, C.P.; van de Veerdonk, F.L.; Tol, J.; van der Meer, J.W.M.; Kullberg, B.J.; Netea, M.G.

    2012-01-01

    Chronic esophageal candidiasis is an infection that is mostly seen in immunocompromised conditions, among which is chronic mucocutaneous candidiasis (CMC). Recently an association between CMC and esophageal carcinoma has been reported. Here we present two patients with chronic esophageal candidiasis who developed esophageal squamous cell carcinoma and we discuss the etiologic role of Candida-induced nitrosamine production, the loss of STAT1 function and impaired tumor surveillance and T-lymphocyte function in the development of esophageal carcinoma. PMID:24371724

  15. Esophageal stents: when and how.

    PubMed

    Kachaamy, Toufic; Pannala, Rahul

    2016-06-01

    Esophageal stents are devices used to alleviate dysphagia and treat leaks and perforations. Successful esophageal stenting requires definition of the abnormal anatomy such as stricture length or location of the leak, proper stent selection and deployment. This requires detailed knowledge of characteristics of the currently available stents. Self-expanding metal stents whether fully or partially covered have become the mainstay of treatment of esophageal cancer-related dysphagia as they provide quick relief of symptoms and have a favorable safety and efficacy profile, compared to other modalities such as radiation, laser, and argon plasma coagulation. They are also the initial treatment of choice for both malignant and benign fistulae. Stents are also used in benign refractory strictures but long-term stricture resolution rates are low in this setting. Fully covered metal stents are relatively easier to remove compared to partially covered stents; optimal time interval for removal depends on the indication for stenting and the clinical status of the patient. Stent related adverse events include chest pain, reflux, migration, and recurrent obstruction. Serious adverse events occur in less than 5% with procedure-related mortality of less than 2%. Techniques such as placement of hemostatic clips, Over The Scope clips, and endoscopic suturing are being used to decrease the migration risk but the optimal approach has not been defined. Antireflux measures are needed when a stent is placed across the gastroesophageal junction. Stents with antireflux designs do not appear to offer additional benefit compared to the conventional stent designs. Newer stent designs including biodegradable, drug eluting and radioactive stents are currently being investigated. PMID:26824424

  16. Endoscopic management of esophageal varices.

    PubMed

    Poza Cordon, Joaquin; Froilan Torres, Consuelo; Burgos García, Aurora; Gea Rodriguez, Francisco; Suárez de Parga, Jose Manuel

    2012-07-16

    The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix. The two principal methods available for esophageal varices are endoscopic sclerotherapy (EST) and band ligation (EBL). The advantages of EST are that it is cheap and easy to use, and the injection catheter fits through the working channel of a diagnostic gastroscope. Endoscopic variceal ligation obliterates varices by causing mechanical strangulation with rubber bands. The following review aims to describe the utility of EBL and EST in different situations, such as acute bleeding, primary and secondary prophylaxis. PMID:22816012

  17. Comparison of absolute intensity between EAS with gamma-families and general EAS at Mount Norikura

    NASA Technical Reports Server (NTRS)

    Mitsumune, T.; Nakatsuka, T.; Nishikawa, K.; Saito, T.; Sakata, M.; Shima, M.; Yamamoto, Y.; Dake, S.; Kawamoto, M.; Kusumose, M.

    1985-01-01

    Gamma-families with total energy greater than 10 TeV, found in the EX chamber which was cooperated with the EAS array were combined with EAS triggered by big bursts. The absolute intensity of the size spectrum of these combined EAS was compared with that of general EAS obtained by AS trigger. The EAS with sizes greater than 2x1 million were always accompanied by gamma-families with sigma E sub gamma H 10 TeV, n sub gamma, H 2 and Emin=3 TeV, although the rate of EAS accompaning such gamma-families decreases rapidly as their sizes decrease.

  18. Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer

    ClinicalTrials.gov

    2016-04-25

    Esophageal Adenocarcinoma; Gastric Adenocarcinoma; Stage IIB Gastric Cancer; Stage IIIA Esophageal Adenocarcinoma; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Adenocarcinoma; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Adenocarcinoma; Stage IIIC Gastric Cancer

  19. Survival Effect of Neoadjuvant Radiotherapy Before Esophagectomy for Patients With Esophageal Cancer: A Surveillance, Epidemiology, and End-Results Study

    SciTech Connect

    Schwer, Amanda L. Ballonoff, Ari; McCammon, Robert; Rusthoven, Kyle; D'Agostino, Ralph B.; Schefter, Tracey E.

    2009-02-01

    Purpose: The role of neoadjuvant radiotherapy (NeoRT) before definitive surgery for esophageal cancer remains controversial. This study used a large population-based database to assess the effect of NeoRT on survival for patients treated with definitive surgery. Methods and Materials: The overall survival (OS) and cause-specific survival for patients with Stage T2-T4, any N, M0 (cT2-T4M0) esophageal cancer who had undergone definitive surgery between 1998 and 2004 were analyzed by querying the Surveillance, Epidemiology, and End-Results database. Kaplan-Meier survival curves were generated and univariate comparisons were made using the log-rank test. Cox proportional hazards survival regression multivariate analysis was performed with NeoRT, T stage (T2 vs. T3-T4), pathologic nodal status (pN0 vs. pN1), number of nodes dissected (>10 vs. {<=}10), histologic type (adenocarcinoma vs. squamous cell carcinoma), age (<65 vs. {>=}65 years), and gender as covariates. Results: A total of 1,033 patients were identified. Of these, 441 patients received NeoRT and 592 underwent esophagectomy alone; 77% were men, 67% had adenocarcinoma, and 72% had Stage T3-T4 disease. The median OS and cause-specific survival were both significantly greater for patients who received NeoRT compared with esophagectomy alone (27 vs. 18 months and 35 vs. 21 months, respectively, p <0.0001). The 3-year OS rate was also significantly greater in the NeoRT group (43% vs. 30%). On multivariate analysis, NeoRT, age <65 years, adenocarcinoma histologic type, female gender, pN0 status, >10 nodes dissected, and Stage T2 disease were all independently correlated with increased OS. Conclusion: These results support the use of NeoRT for patients with esophageal cancer. Prospective studies are needed to confirm these results.

  20. In vivo molecular imaging of HER2 expression in a rat model of Barrett's esophagus adenocarcinoma.

    PubMed

    Realdon, S; Dassie, E; Fassan, M; Dall'Olmo, L; Hatem, G; Buda, A; Arcidiacono, D; Diamantis, G; Zhang, H; Greene, M I; Sturniolo, G C; Rugge, M; Alberti, A; Battaglia, G

    2015-01-01

    Human epidermal growth factor receptor 2 (HER2) is involved in the malignant progression of several human cancers, including esophageal adenocarcinoma (EAC). The purpose of this study was to evaluate HER2 overexpression and to explore the feasibility of confocal laser endomicroscopy for in vivo molecular imaging of HER2 status in an animal model of Barrett's-related EAC. Rats underwent esophagojejunostomy with gastric preservation. At 30 weeks post-surgery, the esophagus of 46 rats was studied; endoscopic and histological findings were correlated with HER2 immunofluorescence on excised biopsies and gross specimens. At this age, 23/46 rats developed Barrett's esophagus (BE), and 6/46 had cancer (four EAC and two squamous cell carcinomas). A significant overexpression of HER2 was observed in esophageal adenocarcinoma compared with normal squamous esophagus (9.4-fold) and BE (6.0-fold). AKT and its phosphorylated form were also overexpressed in cancer areas. Molecular imaging was performed at 80 weeks post-surgery in four rats after tail injection of fluorescent-labeled anti-HER2 antibody. At this age, 3/4 rats developed advance adenocarcinoma and showed in vivo overexpression of HER2 by molecular confocal laser endomicroscopy with heterogeneous distribution within cancer; no HER2 signal was observed in normal or Barrett's tissues. Therefore, HER2 overexpression is a typical feature of the surgical induced model of EAC that can be easily quantified in vivo using an innovative mini-invasive approach including confocal endomicroscopy; this approach may avoid limits of histological evaluation of HER2 status on 'blinded' biopsies. PMID:24708360

  1. Genetic and environmental factors in the etiology of esophageal atresia and/or tracheoesophageal fistula: an overview of the current concepts.

    PubMed

    Felix, Janine F; de Jong, Elisabeth M; Torfs, Claudine P; de Klein, A; Rottier, Robbert J; Tibboel, Dick

    2009-09-01

    Esophageal atresia and/or tracheoesophageal fistula (EA/TEF) are severe congenital anomalies. Although recent years have brought significant improvement in clinical treatment, our understanding of the etiology of these defects is lagging. Many genes and genetic pathways have been implicated in the development of EA/TEF, but only a few genes have been shown to be involved in humans, in animals, or in both. Extrapolating data from animal models to humans is not always straightforward. Environmental factors may also carry a risk, but the mechanisms are yet to be elucidated. This review gives an overview of the current state of knowledge about both genetic and environmental risk factors in the etiology of EA/TEF. PMID:19452513

  2. High Intrathoracic Anastomosis with Thoracoscopy Is Safe and Feasible for Treatment of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Jeon, Hyun Woo; Park, Jae Kil; Song, Kyo Young; Sung, Sook Whan

    2016-01-01

    Background Minimally invasive esophagectomy (MIE) has the potential to reduce the morbidity and mortality of esophageal cancer surgery. Esophageal squamous cell carcinoma (ESCC) has a high incidence of earlier lymphatic spread and is usually located more proximal to the incisor than esophageal adenocarcinoma; consequently, the anastomosis should be made more proximal in the thorax or in the neck. We adopted the proximal intrathoracic anastomotic technique using thoracoscopy for mid-to-lower ESCC. Methods From October 2010 to August 2014, fifty-eight consecutive patients underwent MIE for ESCC. After laparoscopic gastric tubing, thoracoscopic esophageal resection and reconstruction were performed using a 28-mm circular stapler following radical mediastinal lymph node dissection. We tried to make an anastomosis at the apex of the chest. Postoperative outcomes, including overall survival and recurrence, were assessed. Results The mean patient age was 64.3±9 years. The mean operative time was 371.8±51.6 minutes, and the duration of the thorax procedure was 254.8±38.3 minutes. The mean number of lymph nodes dissected was 31±11.7. The mean intensive care unit (ICU) stay and hospital stay were 3.5±8.2 hours and 13.6±7.4 days, respectively. The level of anastomosis was 22.3±1.8cm from the incisor. One patient died of uncontrolled sepsis due to necrosis of the gastric graft. Two patients developed small contained leakage. Nine patients exhibited distant metastasis during the follow-up period. Conclusion Thoracoscopic intrathoracic anastomosis at the proximal esophagus is feasible and safe. PMID:27011160

  3. MicroRNA Expression Differentiates Squamous Epithelium from Barrett’s Esophagus and Esophageal Cancer

    PubMed Central

    Garman, Katherine S.; Owzar, Kouros; Hauser, Elizabeth R.; Westfall, Kristen; Anderson, Blair R.; Souza, Rhonda F.; Diehl, Anna Mae; Provenzale, Dawn; Shaheen, Nicholas J.

    2013-01-01

    Background Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed. Aims We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett’s esophagus (BE), and EAC. Methods We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n=11), BE (n=14), and high-grade dysplasia (HGD)/EAC (n=11). RNA was assessed using microarrays representing 847 human microRNAs followed by qRT-PCR verification of nine microRNAs. In a second cohort (n=18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs. Results After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo. Conclusions These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC. PMID:23925817

  4. Minimally invasive esophagectomy for esophageal cancer – results of surgical therapy

    PubMed Central

    Vrba, Radek; Vomáčková, Katherine; Bohanes, Tomáš; Stašek, Martin; Neoral, Čestmír

    2015-01-01

    Introduction The indication for minimally invasive esophagectomy (MIE) in esophageal cancer has an increasing tendency. Aim To present our cohort of patients operated on between 2006 and 2012. Material and methods: A single centre study of 106 consecutive esophagectomies performed for esophageal cancer by a minimally invasive approach in 79 patients was performed. Transhiatal laparoscopic esophagectomy (THLE) was performed in 66 patients, transthoracic esophagectomy (TTE) in 13 patients, with histological findings of squamous cell carcinoma in 28 and adenocarcinoma in 51 patients. Results The MIE was completed in 76 (96.2%) patients. In cases of TTE, the operation was converted to an open procedure in 3 cases. Operation time ranged from 225 to 370 min (average 256 min). The number of lymph nodes removed was 7–16 (11 on average). The postoperative course was without any complications in 54 (68.3%) patients. Respiratory complications were observed in 14 (17.7%) patients (9 following THLE, 5 following TTE). Other serious complications included acute myocardial infarction (1 patient) and necrosis of the gastroplasty (1 patient). Anastomotic dehiscence was observed in 8 patients, left recurrent laryngeal nerve paralysis in 8 patients, intra-abdominal abscesses in 2 patients, and pleural empyema in 1 case. The overall morbidity of patients operated on by MIE was 31.6%. Thirty-day mortality was 10.1%. Conclusions The MIE belongs to the therapeutic portfolio of surgical procedures performed for esophageal cancer. Successful performance requires erudition of the surgical team in both minimally invasive procedures as well as in classical surgical treatment of esophageal cancer; therefore centralization of patients is imperative. PMID:26240618

  5. Esophageal motility abnormalities in gastroesophageal reflux disease

    PubMed Central

    Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

    2014-01-01

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett’s esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted. PMID:24868489

  6. Esophageal atresia in newborns: a wide spectrum from the isolated forms to a full VACTERL phenotype?

    PubMed Central

    2013-01-01

    Background VATER association was first described in 1972 by Quan and Smith as an acronym which identifies a non-random co-occurrence of Vertebral anomalies, Anal atresia, Tracheoesophageal fistula and/or Esophageal atresia, Radial dysplasia. It is even possible to find out Cardiovascular, Renal and Limb anomalies and the acronym VACTERL was adopted, also, embodying Vascular, as single umbilical artery, and external genitalia anomalies. Methods Data on patients with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) admitted in the Neonatal Intensive Care Unit (NICU) between January 2003 and January 2013 were evaluated for the contingent occurrence of typical VACTERL anomalies (VACTERL-type) and non tipical VACTERL anomalies (non-VACTERL-type). The inclusion criterion was the presence of EA with or without TEF plus two or more of the following additional malformations: vertebral defects, anal atresia, cardiovascular defects, renal anomalies and lower limb deformities, like radial dysplasia. Results Among 52 patients with EA/TEF, 20 (38,4%) had isolated EA and 7 (21,8%) had a recognized etiology such a syndrome and therefore were excluded. Among 32 infants with EA and associated malformations, 15 (46,8%) had VACTERL association. The most common anomalies were congenital heart defects (73,3%), followed by vertebral anomalies (66,6%). Many patients also had additional non-VACTERL-type defects. Single umbilical artery was the most common one followed by nervous system abnormalities and anomalies of toes. Between the groups of infants with VACTERL type and non-VACTERL-type anomalies, there are several overlapping data regarding both the tipically described spectrum and the most frequently reported non-VACTERL-type malformations. Thus, it is possible to differentiate infants with a full phenotype (VACTERL full phenotype) and patients that do not meet all the criteria mentioned above, but with some homologies with the first group (VACTERL partial phenotype). Conclusion The high frequency of non-VACTERL-type anomalies encountered in full and partial phenotype patients would suggest the need for an extension of the clinical criteria for the diagnosis of VACTERL association and also for pre- and post-operative management and follow-up in the short and long term. PMID:23842449

  7. CARE—Pediatric Colon Adenocarcinoma

    PubMed Central

    Koh, King-Jun; Lin, Lung-Huang; Huang, Shih-Hung; Wong, Jia-Uei

    2015-01-01

    Abstract Colon carcinoma is a rare disease in the pediatric population. Here is a report on a 17-year-old male adolescent with colon adenocarcinoma who presented with recurrent epigastric colic pain for 1 month. Diagnostic laparoscopic surgery revealed a 3.2 × 3 cm tumor at the ascending colon, with serosal involvement and peritoneal metastasis. Clinical differences of colorectal carcinoma among children and adults are reviewed and summarized. PMID:25674743

  8. [Oral blastomycosis, laryngeal papillomatosis and esophageal tuberculosis].

    PubMed

    Montoya, Manuel; Chumbiraico, Robert; Ricalde, Melvin; Cazorla, Ernesto; Hernández-Córdova, Gustavo

    2012-06-01

    Esophageal involvement is an extremely rare complication of tuberculosis even in countries with high prevalence of infection. We report the case of a 57 year-old hiv-seronegative patient with simultaneous diagnoses of oral blastomycosis and laryngeal papillomatosis. Both were confirmed by anatomopathological analysis. The esophageal biopsy revealed granulomatous esophagitis with necrosis and ziehl-neelsen stain showed acid-fast alcohol resistant bacilli suggestive of tuberculosis. The patient's history included pulmonary tuberculosis twice and previous abandonment of therapy. Thus, it was necessary to use oral itraconazole combined with second-line anti-tuberculosis drugs administered through a gastrostomy tube. The clinical development was favorable. PMID:22858774

  9. [Dietary and pharmacological aspects of eosinophilic esophagitis].

    PubMed

    Kocsis, Dorottya; Tulassay, Zsolt; Juhász, Márk

    2015-06-01

    Eosinophilic esophagitis is considered to be a chronic antigen-driven disease whereby food and/or aeroallergens induce a chronic inflammatory infiltrate in the esophagus leading to pathological hyperplasia of the epithelial and muscular layers, fibrosis of the lamina propria and symptoms of dysphagia and food impaction. Eosinophilic esophagitis is often associated with other allergic diseases such as asthma or atopic dermatitis. Current first line treatments of the disease include strict dietary modification and topical anti-inflammatory steroids. In this review the authors summarize currently available treatment strategies of eosinophilic esophagitis. PMID:26027600

  10. Esophageal stenosis with sloughing esophagitis: A curious manifestation of graft-vs-host disease.

    PubMed

    Trabulo, Daniel; Ferreira, Sara; Lage, Pedro; Rego, Rafaela Lima; Teixeira, Gilda; Pereira, A Dias

    2015-08-14

    We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years, complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation, corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease, ulceration, esophageal webs, casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context. PMID:26290649

  11. Esophageal stenosis with sloughing esophagitis: A curious manifestation of graft-vs-host disease

    PubMed Central

    Trabulo, Daniel; Ferreira, Sara; Lage, Pedro; Rego, Rafaela Lima; Teixeira, Gilda; Pereira, A Dias

    2015-01-01

    We report a case of a 56-year-old woman with a history of allogenic bone marrow transplantation for two years, complaining with dysphagia and weight loss. Upper endoscopy revealed esophageal stenosis and extensive mucosa sloughing. Biopsies confirmed the diagnosis of graft-vs-host disease (GVHD). Balloon dilation, corticosteroids and cyclosporin resulted in marked clinical improvement. Gastrointestinal tract is involved in the majority of patients with chronic GVHD. Esophageal manifestations are rare and include vesiculobullous disease, ulceration, esophageal webs, casts or strictures. Sloughing esophagitis along with severe stenosis requiring endoscopic dilation has never been reported in this context. PMID:26290649

  12. Esophageal stent placement as a therapeutic option for iatrogenic esophageal perforation in children

    PubMed Central

    Ahmad, Alsafadi; Wong Kee Song, Louis M.; Absah, Imad

    2016-01-01

    Iatrogenic esophageal perforation (IEP) is a potentially serious adverse event of interventional endoscopy. The approach to IEP varies from surgical repair for large perforations to conservative treatment for small contained perforations. We report a case of an 18-month-old girl with congenital esophageal stenosis suffering a large esophageal perforation after a trial of stricture dilatation, which was successfully managed by the placement of fully covered stent. Hence, in selected cases, esophageal stent placement is a feasible alternative to invasive surgery in managing IEP.

  13. Risk of adenocarcinoma of the stomach and esophagus with meat cooking method and doneness preference.

    PubMed

    Ward, M H; Sinha, R; Heineman, E F; Rothman, N; Markin, R; Weisenburger, D D; Correa, P; Zahm, S H

    1997-03-28

    Meats cooked at high temperatures (frying, grilling) and for a long duration contain heterocyclic amines (HCAs), which are both mutagens and animal carcinogens. Additionally, barbecuing/grilling of meats produces polycyclic aromatic hydrocarbons (PAHs). Consumption of well-done meat has been associated with an increased risk of colon cancer but has not been evaluated as a risk factor for stomach or esophageal cancers. We conducted a population-based case-control study in 66 counties of eastern Nebraska. Telephone interviews were conducted with white men and women diagnosed with adenocarcinoma of the stomach (n = 176) and esophagus (n = 143) between July 1988 and June 1993 and 502 controls. The dietary assessment included several questions about usual cooking methods for meats and doneness preference for beef. High intake of red meat was associated with increased risks for both stomach and esophageal cancers. Overall, broiling or frying of beef, chicken or pork was not associated with the risk of these tumors. Barbecuing/grilling, reported as the usual cooking method for a small number of study participants, was associated with an elevated risk of stomach and esophageal cancers. After excluding those who reported usually barbecuing/grilling, a source of both PAHs and HCAs, we evaluated doneness level as a surrogate for HCA exposure. Compared to a preference for rare/medium rare beef, odds ratios were 2.4 for medium, 2.4 for medium well and 3.2 for well done, a significant positive trend. Doneness level was not associated with a significant trend in risk of esophageal cancer. PMID:9096659

  14. Age effects and temporal trends in adenocarcinoma of the esophagus and gastric cardia (United States).

    PubMed

    Jeon, Jihyoun; Luebeck, E Georg; Moolgavkar, Suresh H

    2006-09-01

    A number of hypotheses have been advanced to explain the rapid increase of the incidence of esophageal adenocarcinoma in the US. A major problem in identifying and understanding the nature of this increase is the difficulty in untangling age effects from temporal trends due to cohort and period effects. To address this problem, we have developed multi-stage carcinogenesis models that describe the age-specific incidence of adenocarcinoma of the esophagus and of the gastric cardia with separate adjustments for temporal trends. These models explicitly incorporate important features of the cancers, such as the metaplastic conversion of normal esophagus to Barrett's esophagus (BE). We fit these models separately to the incidence of adenocarcinoma of the esophagus and of the gastric cardia reported in the Surveillance Epidemiology and End Results (SEER) registry over the period 1973-2000. We conclude that the incidence of both cancers is consistent with a sequence that posits a tissue conversion step in the target organ followed by a multi-stage process with three rate-limiting events, the first two leading to an initiated cell that can expand clonally into a premalignant lesion, and the third converting an initiated cell into a malignant cell. Temporal trends in the incidence of both cancers are dominated by dramatically increasing period effects. PMID:16841264

  15. Ordering of mutations in preinvasive disease stages of esophageal carcinogenesis

    PubMed Central

    Forshew, Tim; Barbera, Mariagnese; Murtaza, Muhammed; Ong, Chin-Ann J.; Lao-Sirieix, Pierre; Dunning, Mark J; Smith, Laura; Smith, Mike L.; Anderson, Charlotte L.; Carvalho, Benilton; O’Donovan, Maria; Underwood, Timothy J.; May, Andrew P; Grehan, Nicola; Hardwick, Richard; Davies, Jim; Oloumi, Arusha; Aparicio, Sam; Caldas, Carlos; Eldridge, Matthew D.; Edwards, Paul A.W.; Rosenfeld, Nitzan; Tavaré, Simon; Fitzgerald, Rebecca C

    2014-01-01

    Cancer genome sequencing studies have identified numerous driver genes but the relative timing of mutations in carcinogenesis remains unclear. The gradual progression from pre-malignant Barrett’s esophagus to esophageal adenocarcinoma (EAC) provides an ideal model to study the ordering of somatic mutations. We identified recurrently-mutated genes and assessed clonal structure using whole-genome sequencing and amplicon-resequencing of 112 EACs. We next screened a cohort of 109 biopsies from two key transition points in the development of malignancy; benign metaplastic never-dysplastic Barrett’s esophagus (NDBE, n=66), and high-grade dysplasia (HGD, n=43). Unexpectedly, the majority of recurrently mutated genes in EAC were also mutated in NDBE. Only TP53 and SMAD4 were stage-specific, confined to HGD and EAC, respectively. Finally, we applied this knowledge to identify high-risk Barrett’s esophagus in a novel non-endoscopic test. In conclusion, mutations in EAC driver genes generally occur exceptionally early in disease development with profound implications for diagnostic and therapeutic strategies. PMID:24952744

  16. Multidisciplinary management for esophageal and gastric cancer

    PubMed Central

    Boniface, Megan M; Wani, Sachin B; Schefter, Tracey E; Koo, Phillip J; Meguid, Cheryl; Leong, Stephen; Kaplan, Jeffrey B; Wingrove, Lisa J; McCarter, Martin D

    2016-01-01

    The management of esophageal and gastric cancer is complex and involves multiple specialists in an effort to optimize patient outcomes. Utilizing a multidisciplinary team approach starting from the initial staging evaluation ensures that all members are in agreement with the plan of care. Treatment selection for esophageal and gastric cancer often involves a combination of chemotherapy, radiation, surgery, and palliative interventions (endoscopic and surgical), and direct communication between specialists in these fields is needed to ensure appropriate clinical decision making. At the University of Colorado, the Esophageal and Gastric Multidisciplinary Clinic was created to bring together all experts involved in treating these diseases at a weekly conference in order to provide patients with coordinated, individualized, and patient-centered care. This review details the essential elements and benefits of building a multidisciplinary program focused on treating esophageal and gastric cancer patients. PMID:27217796

  17. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal prosthesis... of a plastic, metal, or polymeric material that is intended to be implanted to restore the...

  18. Esophageal papilloma: Flexible endoscopic ablation by radiofrequency

    PubMed Central

    del Genio, Gianmattia; del Genio, Federica; Schettino, Pietro; Limongelli, Paolo; Tolone, Salvatore; Brusciano, Luigi; Avellino, Manuela; Vitiello, Chiara; Docimo, Giovanni; Pezzullo, Angelo; Docimo, Ludovico

    2015-01-01

    Squamous papilloma of the esophagus is a rare benign lesion of the esophagus. Radiofrequency ablation is an established endoscopic technique for the eradication of Barrett esophagus. No cases of endoscopic ablation of esophageal papilloma by radiofrequency ablation (RFA) have been reported. We report a case of esophageal papilloma successfully treated with a single session of radiofrequency ablation. Endoscopic ablation of the lesion was achieved by radiofrequency using a new catheter inserted through the working channel of endoscope. The esophageal ablated tissue was removed by a specifically designed cup. Complete ablation was confirmed at 3 mo by endoscopy with biopsies. This case supports feasibility and safety of as a new potential indication for BarrxTM RFA in patients with esophageal papilloma. PMID:25789102

  19. Esophageal papilloma: Flexible endoscopic ablation by radiofrequency.

    PubMed

    Del Genio, Gianmattia; Del Genio, Federica; Schettino, Pietro; Limongelli, Paolo; Tolone, Salvatore; Brusciano, Luigi; Avellino, Manuela; Vitiello, Chiara; Docimo, Giovanni; Pezzullo, Angelo; Docimo, Ludovico

    2015-03-16

    Squamous papilloma of the esophagus is a rare benign lesion of the esophagus. Radiofrequency ablation is an established endoscopic technique for the eradication of Barrett esophagus. No cases of endoscopic ablation of esophageal papilloma by radiofrequency ablation (RFA) have been reported. We report a case of esophageal papilloma successfully treated with a single session of radiofrequency ablation. Endoscopic ablation of the lesion was achieved by radiofrequency using a new catheter inserted through the working channel of endoscope. The esophageal ablated tissue was removed by a specifically designed cup. Complete ablation was confirmed at 3 mo by endoscopy with biopsies. This case supports feasibility and safety of as a new potential indication for Barrx(TM) RFA in patients with esophageal papilloma. PMID:25789102

  20. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal prosthesis... of a plastic, metal, or polymeric material that is intended to be implanted to restore the...

  1. Clinical application of endoscopic ultrasonography for esophageal achalasia.

    PubMed

    Minami, Hitomi; Inoue, Haruhiro; Isomoto, Hajime; Urabe, Shigetoshi; Nakao, Kazuhiko

    2015-04-01

    Endoscopic ultrasonography (EUS) has been widely used for evaluating the nature of diseases of various organs. The possibility of applying EUS for esophageal motility diseases has not been well discussed despite its versatility. At present, peroral endoscopic myotomy (POEM) for esophageal achalasia and related diseases has brought new attention to esophageal diseases because POEM provides a more direct approach to the inner structures of the esophageal wall. In the present study, we discuss the clinical utility of EUS in evaluating and treating esophageal motility diseases such as esophageal achalasia and related diseases. PMID:25573637

  2. Mechanisms of Disease of Eosinophilic Esophagitis.

    PubMed

    Davis, Benjamin P; Rothenberg, Marc E

    2016-05-23

    Eosinophilic esophagitis (EoE) is a recently recognized inflammatory disease of the esophagus with clinical symptoms derived from esophageal dysfunction. The etiology of EoE is now being elucidated, and food hypersensitivity is emerging as the central cornerstone of disease pathogenesis. Herein, we present a thorough picture of the current clinical, pathologic, and molecular understanding of the disease with a focus on disease mechanisms. PMID:26925500

  3. Paired exome analysis of Barrett's esophagus and adenocarcinoma.

    PubMed

    Stachler, Matthew D; Taylor-Weiner, Amaro; Peng, Shouyong; McKenna, Aaron; Agoston, Agoston T; Odze, Robert D; Davison, Jon M; Nason, Katie S; Loda, Massimo; Leshchiner, Ignaty; Stewart, Chip; Stojanov, Petar; Seepo, Sara; Lawrence, Michael S; Ferrer-Torres, Daysha; Lin, Jules; Chang, Andrew C; Gabriel, Stacey B; Lander, Eric S; Beer, David G; Getz, Gad; Carter, Scott L; Bass, Adam J

    2015-09-01

    Barrett's esophagus is thought to progress to esophageal adenocarcinoma (EAC) through a stepwise progression with loss of CDKN2A followed by TP53 inactivation and aneuploidy. Here we present whole-exome sequencing from 25 pairs of EAC and Barrett's esophagus and from 5 patients whose Barrett's esophagus and tumor were extensively sampled. Our analysis showed that oncogene amplification typically occurred as a late event and that TP53 mutations often occurred early in Barrett's esophagus progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data showed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations, with more frequent oncogenic amplification and less frequent inactivation of tumor suppressors, including CDKN2A. These data suggest that many EACs emerge not through the gradual accumulation of tumor-suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by the acquisition of oncogenic amplifications. PMID:26192918

  4. Paired Exome Analysis of Barrett’s Esophagus and Adenocarcinoma

    PubMed Central

    Stachler, Matthew D.; Taylor-Weiner, Amaro; Peng, Shouyong; McKenna, Aaron; Agoston, Agoston T.; Odze, Robert D.; Davison, Jon M.; Nason, Katie S.; Loda, Massimo; Leshchiner, Ignaty; Stewart, Chip; Stojanov, Petar; Seepo, Sara; Lawrence, Michael S.; Ferrer-Torres, Daysha; Lin, Jules; Chang, Andrew C.; Gabriel, Stacey B.; Lander, Eric S.; Beer, David G.; Getz, Gad; Carter, Scott L.; Bass, Adam J.

    2015-01-01

    Barrett’s esophagus, is thought to progress to esophageal adenocarcinoma (EAC) through a step-wise progression with loss of CDKN2A followed by p53 inactivation and aneuploidy. Here, we present whole exome sequencing from 25 pairs of EAC and Barrett’s and five patients whose Barrett’s and tumor were extensively sampled. Our analysis revealed that oncogene amplification typically occurred as a late event and that TP53 mutations often occur early in Barrett’s progression, including in non-dysplastic epithelium. Reanalysis of additional EAC exome data revealed that the majority (62.5%) of EACs emerged following genome doubling and that tumors with genomic doubling had different patterns of genomic alterations with more frequent oncogenic amplifications and less frequent inactivation of tumor suppressors, including CDKN2A. These data suggest that many EACs emerge not through gradual accumulation of tumor suppressor alterations but rather through a more direct path whereby a TP53-mutant cell undergoes genome doubling, followed by acquisition of oncogenic amplifications. PMID:26192918

  5. Establishing Magnetic Resonance Imaging as an Accurate and Reliable Tool to Diagnose and Monitor Esophageal Cancer in a Rat Model

    PubMed Central

    Kosovec, Juliann E.; Zaidi, Ali H.; Komatsu, Yoshihiro; Kasi, Pashtoon M.; Cothron, Kyle; Thompson, Diane V.; Lynch, Edward; Jobe, Blair A.

    2014-01-01

    Objective To assess the reliability of magnetic resonance imaging (MRI) for detection of esophageal cancer in the Levrat model of end-to-side esophagojejunostomy. Background The Levrat model has proven utility in terms of its ability to replicate Barrett’s carcinogenesis by inducing gastroduodenoesophageal reflux (GDER). Due to lack of data on the utility of non-invasive methods for detection of esophageal cancer, treatment efficacy studies have been limited, as adenocarcinoma histology has only been validated post-mortem. It would therefore be of great value if the validity and reliability of MRI could be established in this setting. Methods Chronic GDER reflux was induced in 19 male Sprague-Dawley rats using the modified Levrat model. At 40 weeks post-surgery, all animals underwent endoscopy, MRI scanning, and post-mortem histological analysis of the esophagus and anastomosis. With post-mortem histology serving as the gold standard, assessment of presence of esophageal cancer was made by five esophageal specialists and five radiologists on endoscopy and MRI, respectively. Results The accuracy of MRI and endoscopic analysis to correctly identify cancer vs. no cancer was 85.3% and 50.5%, respectively. ROC curves demonstrated that MRI rating had an AUC of 0.966 (p<0.001) and endoscopy rating had an AUC of 0.534 (p = 0.804). The sensitivity and specificity of MRI for identifying cancer vs. no-cancer was 89.1% and 80% respectively, as compared to 45.5% and 57.5% for endoscopy. False positive rates of MRI and endoscopy were 20% and 42.5%, respectively. Conclusions MRI is a more reliable diagnostic method than endoscopy in the Levrat model. The non-invasiveness of the tool and its potential to volumetrically quantify the size and number of tumors likely makes it even more useful in evaluating novel agents and their efficacy in treatment studies of esophageal cancer. PMID:24705451

  6. Ileostomy polyps, adenomas, and adenocarcinomas.

    PubMed Central

    Attanoos, R; Billings, P J; Hughes, L E; Williams, G T

    1995-01-01

    Ileostomy polyps are uncommon and poorly described. The aim of this study was to undertake a retrospective clinicopathological review of ileostomy polyps. Seven patients with 60 polyps arising on ileostomies performed for ulcerative colitis were studied. The histopathological evaluation of archival ileostomy biopsy specimens, polypectomy or excision specimens, and clinical review of patient records was undertaken. Fifty of 60 polyps were inflammatory cap polyps and six further polyps were composed of granulation tissue only. They occurred anywhere on the stoma at any time after ileostomy construction and were strongly associated with overt stomal prolapse. Four neoplastic polyps were identified in two patients 27-36 years after ileostomy construction; all occurred at the mucocutaneous junction. One patient presented with a 2 cm polypoid invasive adenocarcinoma while in the second a 1.7 cm polypoid mucinous adenocarcinoma and a 0.7 cm ileal tubular adenoma with high grade dysplasia occurred at the site of excision of a cap polyp showing focal low grade adenomatous dysplasia six years previously. Neoplastic and non-neoplastic polyps could not be differentiated clinically. It was found that most ileostomy polyps are inflammatory cap polyps associated with stomal prolapse. Less common are polypoid adenomas or adenocarcinomas arising at the mucocutaneous anastomosis > 20 years after ileostomy construction. To prevent ileostomy carcinoma it is recommended that a biopsy of all polyps at the mucocutaneous anastomosis and of any non-prolapse associated polyps elsewhere on the stoma occurring > 15 years after ileostomy construction is done. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:8537059

  7. Esophagitis

    MedlinePlus

    ... Surgery or radiation to the chest (for example, treatment for lung cancer) Taking certain medicines without drinking plenty of water. These medicines include alendronate, doxycycline, ibandronate, risedronate, tetracycline, ...

  8. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury

    SciTech Connect

    Korsten, M.A.; Rosman, A.S.; Fishbein, S.; Shlein, R.D.; Goldberg, H.E.; Biener, A. )

    1991-06-01

    OBJECTIVES: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency.

  9. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Environmental Assessment § 651.34 EA components. EAs should be... affected environment and establish the environmental setting against which environmental effects...

  10. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) ENVIRONMENTAL QUALITY ENVIRONMENTAL ANALYSIS OF ARMY ACTIONS (AR 200-2) Environmental Assessment § 651.34 EA components. EAs should be... affected environment and establish the environmental setting against which environmental effects...

  11. Coexistent atypical polypoid adenomyoma and endometrial adenocarcinoma.

    PubMed

    Mittal, K R; Peng, X C; Wallach, R C; Demopoulos, R I

    1995-05-01

    Atypical polypoid adenomyoma (APA) is a rare entity that is believed to follow a benign course. We report a case of APA with coexistent endometrial adenocarcinoma. The example raises the possibility that APA may progress to endometrial adenocarcinoma in some cases. PMID:7750942

  12. Conjunctival metastatic adenocarcinoma of unknown origin.

    PubMed

    Li, He J; Tsaousis, Konstantinos T; Hoopes, Phillip; Mamalis, Nick

    2016-01-01

    We describe the case of a presumed metastatic adenocarcinoma discovered in the conjunctival limbus of a 75-year-old male with a history of prostate adenocarcinoma. After an initial clinical diagnosis of pinguecula and unsuccessful topical steroid therapy, the lesion was excised and sent for pathological evaluation and special staining. The histopathological evaluation was consistent with a diagnosis of adenocarcinoma, without evidence of lacrimal tissue. Surprisingly, results from special staining were most consistent with lung adenocarcinoma rather than that from a prostate origin. Systemic radiographic evaluation did not locate the primary tumour, and the patient did not present with any symptoms consistent with malignancy. Watchful waiting was chosen as the therapeutic strategy to manage the patient. This is the first report of an adenocarcinoma, likely metastatic, at the conjunctival limbus. PMID:27190113

  13. Obligate progression precedes lung adenocarcinoma dissemination

    PubMed Central

    Caswell, Deborah R.; Chuang, Chen-Hua; Yang, Dian; Chiou, Shin-Heng; Cheemalavagu, Shashank; Kim-Kiselak, Caroline; Connolly, Andrew; Winslow, Monte M.

    2014-01-01

    Despite its clinical importance, very little is known about the natural history and molecular underpinnings of lung cancer dissemination and metastasis. Here we employed a genetically-engineered mouse model of metastatic lung adenocarcinoma in which cancer cells are fluorescently marked to determine whether dissemination is an inherent ability or a major acquired phenotype during lung adenocarcinoma metastasis. We find very little evidence for dissemination from oncogenic Kras-driven hyperplasias or most adenocarcinomas. p53 loss is insufficient to drive dissemination but rather enables rare cancer cells in a small fraction of primary adenocarcinomas to gain alterations that drive dissemination. Molecular characterization of disseminated tumors cells indicates that down-regulation of the transcription factor Nkx2-1 precedes dissemination. Finally, we show that metastatic primary tumors possess a highly proliferative sub-population of cells with characteristics matching those of disseminating cells. We propose that dissemination is a major hurdle during the natural course of lung adenocarcinoma metastasis. PMID:24740995

  14. Uterine adenocarcinoma with feline leukemia virus infection

    PubMed Central

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa

    2011-01-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection. PMID:22232645

  15. Evaluation of Esophageal Motor Function With High-resolution Manometry

    PubMed Central

    2013-01-01

    For several decades esophageal manometry has been the test of choice to evaluate disorders of esophageal motor function. The recent introduction of high-resolution manometry for the study of esophageal motor function simplified performance of esophageal manometry, and revealed previously unidentified patterns of normal and abnormal esophageal motor function. Presentation of pressure data as color contour plots or esophageal pressure topography led to the development of new tools for analyzing and classifying esophageal motor patterns. The current standard and still developing approach to do this is the Chicago classification. While this methodical approach is improving our diagnosis of esophageal motor disorders, it currently does not address all motor abnormalities. We will explore the Chicago classification and disorders that it does not address. PMID:23875094

  16. [FEATURES OF TREATMENT OF EOSINOPHILIC ESOPHAGITIS IN SCHOOLCHILDREN].

    PubMed

    Horodylovska, M I

    2015-01-01

    The inclusion of probiotic L. reuteri into the complex therapy of eosinophilic esophagitis significantly affect the outcomes of children--there was significant decrease in the number of eosinophils in the esophageal mucosa of children. PMID:26118052

  17. Transabdominal approach assisted by thoracoscopic drainage for lower esophageal perforation

    PubMed Central

    Maki, Harufumi; Azuma, Masaki; Kanamaru, Hitoshi; Nishiyama, Motohiro; Okamoto, Kazuya; Shimamura, Takahiro; Kyo, Kennoki; Maema, Atsushi; Nakamura, Toshio; Shirakawa, Motoaki; Yokoyama, Hidetaro

    2015-01-01

    The effectiveness of use of thoracoscopy for esophageal perforation has not been fully evaluated. We herein report a case of esophageal perforation for which a transabdominal approach assisted by thoracoscopic drainage was performed. PMID:26628716

  18. Evaluation of urgent esophagectomy in esophageal perforation

    PubMed Central

    de AQUINO, José Luis Braga; de CAMARGO, José Gonzaga Teixeira; CECCHINO, Gustavo Nardini; PEREIRA, Douglas Alexandre Rizzanti; BENTO, Caroline Agnelli; LEANDRO-MERHI, Vânia Aparecida

    2014-01-01

    Background Esophageal trauma is considered one of the most severe lesions of the digestive tract. There is still much controversy in choosing the best treatment for cases of esophageal perforation since that decision involves many variables. The readiness of medical care, the patient's clinical status, the local conditions of the perforated segment, and the severity of the associated injuries must be considered for the most adequate therapeutic choice. Aim To demonstrate and to analyze the results of urgent esophagectomy in a series of patients with esophageal perforation. Methods A retrospective study of 31 patients with confirmed esophageal perforation. Most injuries were due to endoscopic dilatation of benign esophageal disorders, which had evolved with stenosis. The diagnosis of perforation was based on clinical parameters, laboratory tests, and endoscopic images. ‪The main surgical technique used was transmediastinal esophagectomy followed by reconstruction of the digestive tract in a second surgical procedure. Patients were evaluated for the development of systemic and local complications, especially for the dehiscence or stricture of the anastomosis of the cervical esophagus with either the stomach or the transposed colon. Results Early postoperative evaluation showed a survival rate of 77.1% in relation to the proposed surgery, and 45% of these patients presented no further complications. The other patients had one or more complications, being pulmonary infection and anastomotic fistula the most frequent. The seven patients (22.9%) who underwent esophageal resection 48 hours after the diagnosis died of sepsis. At medium and long-term assessments, most patients reported a good quality of life and full satisfaction regarding the surgery outcomes. Conclusions Despite the morbidity, emergency esophagectomy has its validity, especially in well indicated cases of esophageal perforation subsequent to endoscopic dilation for benign strictures. PMID:25626932

  19. Chemoprevention of esophageal squamous cell carcinoma

    SciTech Connect

    Stoner, Gary D. Wang Lishu; Chen Tong

    2007-11-01

    Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.

  20. Broken Esophageal Stent Successfully Treated by Interventional Radiology Technique

    SciTech Connect

    Zelenak, Kamil; Mistuna, Dusan; Lucan, Jaroslav; Polacek, Hubert

    2010-06-15

    Esophageal stent fractures occur quite rarely. A 61-year-old male patient was previously treated for rupture of benign stenosis, occurring after dilatation, by implanting an esophageal stent. However, a year after implantation, the patient suffered from dysphagia caused by the broken esophageal stent. He was treated with the interventional radiology technique, whereby a second implantation of the esophageal stent was carried out quite successfully.

  1. Current status of and perspectives regarding neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

    PubMed

    Saeki, Hiroshi; Nakashima, Yuichiro; Zaitsu, Yoko; Tsuda, Yasuo; Kasagi, Yuta; Ando, Koji; Imamura, Yu; Ohgaki, Kippei; Ito, Shuhei; Kimura, Yasue; Egashira, Akinori; Oki, Eiji; Morita, Masaru; Maehara, Yoshihiko

    2016-03-01

    The significance of neoadjuvant chemoradiotherapy (NACRT) for esophageal squamous cell carcinoma (ESCC) remains controversial with regard to the pathological response and long-term survival. We herein review the current status of and future perspectives regarding NACRT followed by esophagectomy for locally advanced ESCC. Some studies have suggested that a pathological complete response with NACRT is more common in patients with ESCC than in those with adenocarcinoma and that NACRT provided a survival benefit limited to patients with ESCC. However, NACRT may increase the risk of postoperative complications after esophagectomy. It is obvious that a favorable pathological response is the most important factor for obtaining a survival benefit, although no established parameters have been implemented clinically to predict the response to NACRT. Prospective clinical studies and basic research studies to identify predictive biomarkers for the response to NACRT are needed to aid in the development of NACRT treatment strategies for patients with ESCC. PMID:25740123

  2. Detection of human papillomavirus in esophageal and gastroesophageal junction tumors: A retrospective study by real-time polymerase chain reaction in an instutional experience from Turkey and review of literature.

    PubMed

    Türkay, Düriye Özer; Vural, Çiğdem; Sayan, Murat; Gürbüz, Yeşim

    2016-02-01

    Esophageal cancer is a poor-prognosis malignancy that ranks eighth among all cancer types, and its prevalence shows differences among geographical regions. Although the most important risk factors for esophageal carcinoma are alcohol and smoking, viral infections, particularly HPV infection, are also considered among etiological agents. Our study aims to detect the presence of HPV in esophageal cancers in our patient population and to investigate its correlation with clinico-pathological parameters. We investigated the presence of HPV-DNA by real-time polymerase chain reaction in a total of 52 patients with esophageal cancer. Subtype analysis was performed in positive cases and was correlated with selected clinico-pathological parameters. Five (9.6%) of 52 tumor samples, 3 squamous cell carcinomas (3/33 cases) and 2 adenocarcinomas (2/19 cases), were HPV-DNA-positive. Subtype analysis could be performed in four HPV-DNA-positive cases, of which three were HPV type-39 and 1 was type-16. The Marmara region, where the present study was carried out, is a region with low-moderate risk for esophageal cancer, and the prevalence of HPV-DNA in these tumors is similar to the prevalence of HPV-DNA reported in the literature for regions with similar risk. In conclusion, we detected HPV DNA in a subset of esophageal and gastroesophageal junction tumors. HPV infection may have a role in esophageal carcinogenesis and high-risk HPV subtypes can particularly be considered among risk factors since the prevalence of high risk HPV infection has also been found to be increased in regions with a high risk for esophageal cancer compared to low-moderate risk regions. PMID:26608416

  3. Recovery of normal esophageal function in a kitten with diffuse megaesophagus and an occult lower esophageal stricture.

    PubMed

    Schneider, Jaycie; Ames, Marisa; DiCicco, Michael; Savage, Mason; Atkins, Clarke; Wood, Michael; Gookin, Jody L

    2015-06-01

    An 8-week-old male domestic shorthair was presented to the Internal Medicine Service at North Carolina State University for regurgitation. Radiographic diagnosis of generalized esophageal dilation and failure of esophageal peristalsis were compatible with diagnosis of congenital megaesophagus. Endoscopic examination of the esophagus revealed a fibrous stricture just orad to the lower esophageal sphincter. Conservative management to increase the body condition and size of the kitten consisted of feeding through a gastrostomy tube, during which time the esophagus regained normal peristaltic function, the stricture orifice widened in size and successful balloon dilatation of the stricture was performed. Esophageal endoscopy should be considered to rule out a stricture near the lower esophageal sphincter in kittens with radiographic findings suggestive of congenital megaesophagus. Management of such kittens by means of gastrostomy tube feeding may be associated with a return of normal esophageal motility and widening of the esophageal stricture, and facilitate subsequent success of interventional dilation of the esophageal stricture. PMID:25030954

  4. Pharmacological Management of Esophageal Food Bolus Impaction

    PubMed Central

    Khayyat, Yasir Mohammed

    2013-01-01

    Background. Soft esophageal bolus impaction is an emergency that requires skilled endoscopic removal if persistent obstructive symptoms do not resolve spontaneously after careful observation. Expedited care of these patients is crucial to avoid respiratory and mechanical complications. Other possible options for management include medical agents used to manage it prior to performing endoscopy if access to endoscopy was not available or declined by the patient. Aim. To review the available pharmacological and other nonmedicinal options and their mechanism of relief for soft esophageal impaction. Method. Pubmed, Medline and Ovid were used for search of MESH terms pertinent including “foreign body, esophageal, esophageal bolus and medical” for pharmacological and non medicinial agents used for management of esophageal soft bolus impaction as well as manual review of the cross-references. Results. Several agents were identified including Buscopan, Glucagon, nitrates, calcium channel blockers, and papaveretum. Non medicinal agents are water, effervescent agents, and papain. No evidence was found to suggest preference or effectiveness of use of a certain pharmacological agent compared to others. Buscopan, Glucagon, benzodiazepines, and nitrates were studied extensively and may be used in selected patients with caution. Use of papain is obsolete in management of soft bolus impaction. PMID:23738071

  5. Esophageal tissue engineering: Current status and perspectives.

    PubMed

    Poghosyan, T; Catry, J; Luong-Nguyen, M; Bruneval, P; Domet, T; Arakelian, L; Sfeir, R; Michaud, L; Vanneaux, V; Gottrand, F; Larghero, J; Cattan, P

    2016-02-01

    Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular "intelligent matrices" that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. PMID:26711880

  6. Molecular staging of lung and esophageal cancer.

    PubMed

    Lau, Christine L; Moore, Mary-Beth H; Brooks, Kelly R; D'Amico, Thomas A; Harpole, David H

    2002-06-01

    In both esophageal and NSCLC, the TNM stage at diagnosis remains the most important determinant of survival. Significant research to investigate the biology of NSCLC and esophageal carcinoma is ongoing, and the roles of proto-oncogenes, tumor suppressor genes, angiogenic factors, extracellular matrix proteases, and adhesion molecules are being elucidated. While evidence is accumulating that various markers are involved in NSCLC and esophageal tumor virulence, the current studies are compromised by small sample sizes, heterogeneous populations, and variations in techniques. Large prospective studies with homogenous groups designed to evaluate the role of these various markers should clarify their potential involvement in NSCLC and esophageal cancer. Identification of occult micrometastases in lymph nodes and bone marrow using immunohistochemical techniques and rt-PCR is intriguing. These techniques are promising as a method to more accurately stage patients, and therefore to predict outcomes and to determine therapies. Perhaps the most promising area of research is the development of novel drugs whose mechanism of action targets the pathways of various molecular markers. Molecular biologic substaging offers an opportunity to individualize a chemotherapeutic regimen based on the molecular profile of the tumor, thus providing the potential for improved outcomes with less morbidity in patients with both NSCLC and esophageal cancer. PMID:12371582

  7. Esophageal surgery in minimally invasive era.

    PubMed

    Bencini, Lapo; Moraldi, Luca; Bartolini, Ilenia; Coratti, Andrea

    2016-01-27

    The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID:26843913

  8. Esophageal surgery in minimally invasive era

    PubMed Central

    Bencini, Lapo; Moraldi, Luca; Bartolini, Ilenia; Coratti, Andrea

    2016-01-01

    The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID:26843913

  9. Esophageal Cancer: Insights From Mouse Models

    PubMed Central

    Tétreault, Marie-Pier

    2015-01-01

    Esophageal cancer is the eighth leading cause of cancer and the sixth most common cause of cancer-related death worldwide. Despite recent advances in the development of surgical techniques in combination with the use of radiotherapy and chemotherapy, the prognosis for esophageal cancer remains poor. The cellular and molecular mechanisms that drive the pathogenesis of esophageal cancer are still poorly understood. Hence, understanding these mechanisms is crucial to improving outcomes for patients with esophageal cancer. Mouse models constitute valuable tools for modeling human cancers and for the preclinical testing of therapeutic strategies in a manner not possible in human subjects. Mice are excellent models for studying human cancers because they are similar to humans at the physiological and molecular levels and because they have a shorter gestation time and life cycle. Moreover, a wide range of well-developed technologies for introducing genetic modifications into mice are currently available. In this review, we describe how different mouse models are used to study esophageal cancer. PMID:26380556

  10. External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

    PubMed Central

    Chang, Chih-Hsien; Liu, Shin-Yi; Chi, Chih-Wen; Yu, Hsiang-Lin; Chang, Tsui-Jung; Tsai, Tung-Hu; Lee, Te-Wei; Chen, Yu-Jen

    2015-01-01

    External beam radiotherapy (EBRT) treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (188Re)-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma) and CE81T/VGH (squamous cell carcinoma) were implanted and compared. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188Re-liposome. The combination of EBRT and 188Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188Re-liposome might be a potential treatment modality for esophageal cancer. PMID:26056445

  11. Endoscopic treatment of esophageal achalasia.

    PubMed

    Esposito, Dario; Maione, Francesco; D'Alessandro, Alessandra; Sarnelli, Giovanni; De Palma, Giovanni D

    2016-01-25

    Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry (HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometric type by HRM are also predictors of responsiveness to treatment. Older patients, females and type II achalasia are better after treatment compared to younger patients, males and type III achalasia. Self-expandable metallic stents are an alternative in patients non responding to conventional therapies. PMID:26839644

  12. Endoscopic treatment of esophageal achalasia

    PubMed Central

    Esposito, Dario; Maione, Francesco; D’Alessandro, Alessandra; Sarnelli, Giovanni; De Palma, Giovanni D

    2016-01-01

    Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry (HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometric type by HRM are also predictors of responsiveness to treatment. Older patients, females and type II achalasia are better after treatment compared to younger patients, males and type III achalasia. Self-expandable metallic stents are an alternative in patients non responding to conventional therapies. PMID:26839644

  13. MLN0264 in Previously Treated Asian Patients With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2015-07-29

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  14. 47 CFR 11.44 - EAS message priorities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS message priorities. 11.44 Section 11.44 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization § 11.44 EAS message priorities. (a) A national activation of the EAS for a Presidential message with the Event code EAN as specified in § 11.31...

  15. 47 CFR 11.15 - EAS Operating Handbook.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false EAS Operating Handbook. 11.15 Section 11.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General 11.15 EAS... at EAS Participant facilities upon receipt of an EAN, an EAT, tests, or State and Local Area...

  16. 47 CFR 11.41 - Participation in EAS.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Participation in EAS. 11.41 Section 11.41 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization 11.41 Participation in EAS. All EAS Participants specified in 11.11 are categorized as Participating National...

  17. 47 CFR 11.41 - Participation in EAS.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Participation in EAS. 11.41 Section 11.41 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization 11.41 Participation in EAS. All EAS Participants specified in 11.11 are categorized as Participating National...

  18. 47 CFR 11.15 - EAS Operating Handbook.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false EAS Operating Handbook. 11.15 Section 11.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General 11.15 EAS... at EAS Participant facilities upon receipt of an EAN, an EAT, tests, or State and Local Area...

  19. 47 CFR 11.41 - Participation in EAS.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Participation in EAS. 11.41 Section 11.41 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization 11.41 Participation in EAS. All EAS Participants specified in 11.11 are categorized as Participating National...

  20. 47 CFR 11.15 - EAS Operating Handbook.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false EAS Operating Handbook. 11.15 Section 11.15 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) General 11.15 EAS... at EAS Participant facilities upon receipt of an EAN, an EAT, tests, or State and Local Area...

  1. 47 CFR 11.46 - EAS public service announcements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false EAS public service announcements. 11.46 Section...) Organization § 11.46 EAS public service announcements. EAS Participants may use Public Service Announcements or obtain commercial sponsors for announcements, infomercials, or programs explaining the EAS to the...

  2. 47 CFR 11.46 - EAS public service announcements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false EAS public service announcements. 11.46 Section...) Organization § 11.46 EAS public service announcements. EAS Participants may use Public Service Announcements or obtain commercial sponsors for announcements, infomercials, or programs explaining the EAS to the...

  3. 47 CFR 11.46 - EAS public service announcements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false EAS public service announcements. 11.46 Section...) Organization § 11.46 EAS public service announcements. EAS Participants may use Public Service Announcements or obtain commercial sponsors for announcements, infomercials, or programs explaining the EAS to the...

  4. 47 CFR 11.46 - EAS public service announcements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false EAS public service announcements. 11.46 Section...) Organization § 11.46 EAS public service announcements. EAS Participants may use Public Service Announcements or obtain commercial sponsors for announcements, infomercials, or programs explaining the EAS to the...

  5. 47 CFR 11.46 - EAS public service announcements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false EAS public service announcements. 11.46 Section...) Organization § 11.46 EAS public service announcements. EAS Participants may use Public Service Announcements or obtain commercial sponsors for announcements, infomercials, or programs explaining the EAS to the...

  6. Trends in Esophageal Cancer Survival in United States Adults from 1973 to 2009: A SEER Database Analysis

    PubMed Central

    Njei, Basile; McCarty, Thomas R.; Birk, John W.

    2016-01-01

    Background The rise in incidence of esophageal cancer (EC) in the United States (U.S.) over the last four decades has been well documented; however, data on trends in long-term survival and impact on modern therapies associated with survival is lacking. Methods The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with confirmed EC. Cox proportional hazard regression was used to determine independent mortality factors. Results Of 93,167 patients diagnosed with EC between 1973 and 2009, 49% had a histologic diagnosis of esophageal adenocarcinoma (EAC). There was an increase (almost double) in the proportion of patients with adenocarcinoma from the 1970's to 2000's (n = 2,350; 35% to n = 32,212; 61%, p<0.001). Surgery was performed for localized disease in a majority of EC regardless of type (n = 46,683; 89%). Use of surgical treatment increased significantly over the study period (49% to 64%, p<0.001). There was also an increase in overall median survival (6 months versus 10 months, p<0.001) and 5-year survival rate (9% to 22%, p<0.001). Median survival increased consistently for EAC and squamous cell carcinoma (SCC) until the 1990's. After this period, median survival of EAC continued to increase more rapidly while SCC remained relatively stable. Conclusion A significant survival improvement in esophageal cancer was seen from 1973 to 2009, largely due to earlier detection at a curative stage and greater utilization of treatment modalities (especially surgery). Despite the rising prevalence, patients with EAC have better long-term survival outcomes than those SCC. PMID:26749521

  7. Minimally invasive esophageal resection and intrathoracic anastomosis for lower thoracic esophageal cancer with single position

    PubMed Central

    Zhao, Lufeng; Ge, Jianjun; Li, Wenshan; Luo, Yaping

    2015-01-01

    There are various esophagectomy approaches for lower thoracic esophageal cancer, and the minimally invasive esophagectomy (MIE) approach shows the advantages of less discomfort, shorter length of stay and a faster recovery to baseline status than open approaches. The current study reports a case of lower thoracic esophageal cancer was treated using a single-position, minimally invasive surgical technique with laparoscopy and thoracoscopy. A 68-year-old man, whose gastroscopy identified the esophageal carcinoma, came to our medical center due to dysphagia for over 1 year. The patient underwent tumor radical resection and intrathoracic anastomosis by laparoscopy and thoracoscopy with single position. The patient has recovered well after the surgery. PMID:26380776

  8. [Benign mimics of prostatic adenocarcinoma].

    PubMed

    Kovylina, M V; Prilepskaia, E A; Govorov, A V; D'iakov, V V; Kolontarev, K B; Vasil'ev, A O; Sidorenkov, A V; Rasner, P I; Glotov, A V; Pushkar', D Iu; Nikitaev, V G; Pronichev, A N

    2014-01-01

    Prostate cancer occupies 2nd place on the prevalence and 6th place on mortality among all cancers in men. That is not to deny the social importance of prostate cancer, but attention is drawn to significant advantage of newly detected cases above the cancer-specific mortality. "Gold standard" for diagnosis includes morphological study of tissue fragments after transrectal multifocal prostate biopsy. The importance of the differential diagnosis is particularly relevant when analyzing fragments of prostate tissue obtained from biopsies as a false positive result may cause unnecessary and excessive treatment. This article presents the most common benign processes that can simulate various grade adenocarcinoma. Awareness about the presence of such cancer mimics and careful examination of micropreparations in most cases allows to come to the correct conclusion. PMID:25799728

  9. MYC and gastric adenocarcinoma carcinogenesis

    PubMed Central

    Calcagno, Danielle Queiroz; Leal, Mariana Ferreira; Assumpção, Paulo Pimentel; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodríguez

    2008-01-01

    MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications. PMID:18932273

  10. [Intraductal adenocarcinoma of the prostate].

    PubMed

    Rabut, B; Comoz, F; Hurel, J P; Bidaud, Y; Cante, P; Bensadoun, H

    2001-06-01

    Three patients with a mean age of 69 years presented with endometrioid carcinoma of the prostate between 1995 and 2000. With a mean follow-up of 17 months, 2 patients are alive without metastases and 1 has died from another cause. Endometrioid carcinoma represents less than 5% of all prostate cancers. Its histological origin has been the subject of controversy for a long time. The clinical presentation is often unusual and the natural history is considered to be more aggressive than that of the glandular form of prostatic cancer. Endometrioid carcinoma of the prostate is not derived from Müllerian structures, but from prostatic tissue. It is an unusual form of prostatic cancer, whose clinical course and treatment are the same as those of adenocarcinoma. PMID:11512473

  11. Implantation of esophageal cancer onto post-dissection ulcer after gastric endoscopic submucosal dissection.

    PubMed

    Asai, Satoshi; Takeshita, Koutarou; Kano, Yuki; Nakao, Eisuke; Ichinona, Takumi; Fujimoto, Naoki; Akamine, Eisuke; Mori, Takuji; Ogawa, Atsuhiro

    2016-03-01

    A case in which implantation of esophageal squamous cell carcinoma onto a post-dissection gastric ulcer was strongly suspected is presented. A 72-year-old man with alcoholic liver cirrhosis underwent esophagogastroduodenoscopy (EGD). Esophageal cancer (EC) (Mt, 20 mm, 0-Is) and gastric cancer (GC) (antrum, 15 mm, 0-IIc) were identified. Biopsy specimens revealed moderately differentiated squamous cell carcinoma (SCC) and differentiated adenocarcinoma, respectively. The GC was resected by endoscopic submucosal dissection (ESD) [14 mm × 9 mm, type 0-IIc, tub1, pT1a(M), ly0, v0, HM(-), VM(-)]. Two months after ESD, radiation therapy was started for the EC, and an almost complete response was obtained. Nine months after the ESD, a follow-up EGD showed a submucosal tumor-like lesion with ulceration, located immediately under the post-ESD scar, and biopsy specimens showed moderately differentiated SCC. There were no similar lesions suggesting hematogenous or lymphatic metastasis in the stomach. PMID:26973424

  12. Enhanced Expression of Fibroblast Growth Factor Receptor 3 IIIc Promotes Human Esophageal Carcinoma Cell Proliferation.

    PubMed

    Ueno, Nobuhiro; Shimizu, Akio; Kanai, Michiyuki; Iwaya, Yugo; Ueda, Shugo; Nakayama, Jun; Seo, Misuzu Kurokawa

    2016-01-01

    Deregulated expression of fibroblast growth factor receptors (FGFRs) and their ligands plays critical roles in tumorigenesis. The gene expression of an alternatively spliced isoforms of FGFR3, FGFR3IIIc, was analyzed by RT-PCR in samples from patients with esophageal carcinoma (EC), including esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). The incidence of FGFR3IIIc was higher in EC [12/16 (75%); p=0.073] than in non-cancerous mucosa (NCM) [6/16 (38%)]. Indeed, an immunohistochemical analysis of early-stage ESCC showed that carcinoma cells expressing FGFR3IIIc stained positively with SCC-112, a tumor marker, and Ki67, a cell proliferation marker, suggesting that the expression of FGFR3IIIc promotes cell proliferation. We used EC-GI-10 cells endogenously expressing FGFR3IIIc as a model of ESCC to provide mechanistic insight into the role of FGFR3IIIc in ESCC. The knockdown of endogenous FGFR3 using siRNA treatment significantly abrogated cell proliferation and the overexpression of FGFR3IIIc in cells with enhanced cell proliferation. EC-GI-10 cells and ESCC from patients with EC showed endogenous expression of FGF2, a specific ligand for FGFR3IIIc, suggesting that the upregulated expression of FGFR3IIIc may create autocrine FGF signaling in ESCC. Taken together, FGFR3IIIc may have the potential to be an early-stage tumor marker and a molecular target for ESCC therapy. PMID:26487184

  13. Useful strategies to prevent severe stricture after endoscopic submucosal dissection for superficial esophageal neoplasm

    PubMed Central

    Uno, Kaname; Iijima, Katsunori; Koike, Tomoyuki; Shimosegawa, Tooru

    2015-01-01

    The minimal invasiveness of endoscopic submucosal dissection (ESD) prompted us to apply this technique to large-size early esophageal squamous cell carcinoma and Barrett’s adenocarcinoma, despite the limitations in the study population and surveillance duration. A post-ESD ulceration of greater than three-fourths of esophageal circumference was advocated as an important risk factor for refractory strictures that require several sessions of dilation therapy. Most of the preoperative conditions are asymptomatic, but dilatation treatment for dysphagia associated with the stricture has potential risks of severe complications and a worsening of quality of life. Possible mechanisms of dysphasia were demonstrated based on dysmotility and pathological abnormalities at the site: (1) delayed mucosal healing; (2) severe inflammation and disorganized fibrosis with abundant extracellular matrices in the submucosa; and (3) atrophy in the muscularis proper. However, reports on the administration of anti-scarring agents, preventive dilation therapies, and regenerative medicine demonstrated limited success in stricture prevention, and there were discrepancies in the study designs and protocols of these reports. The development and consequent long-term assessments of new prophylactic technologies on the promotion of wound healing and control of the inflammatory/tumor microenvironment will require collaboration among various research fields because of the limited accuracy of preoperative staging and high-risk of local recurrence. PMID:26109798

  14. Implantation of esophageal cancer onto post-dissection ulcer after gastric endoscopic submucosal dissection

    PubMed Central

    Asai, Satoshi; Takeshita, Koutarou; Kano, Yuki; Nakao, Eisuke; Ichinona, Takumi; Fujimoto, Naoki; Akamine, Eisuke; Mori, Takuji; Ogawa, Atsuhiro

    2016-01-01

    A case in which implantation of esophageal squamous cell carcinoma onto a post-dissection gastric ulcer was strongly suspected is presented. A 72-year-old man with alcoholic liver cirrhosis underwent esophagogastroduodenoscopy (EGD). Esophageal cancer (EC) (Mt, 20 mm, 0-Is) and gastric cancer (GC) (antrum, 15 mm, 0-IIc) were identified. Biopsy specimens revealed moderately differentiated squamous cell carcinoma (SCC) and differentiated adenocarcinoma, respectively. The GC was resected by endoscopic submucosal dissection (ESD) [14 mm × 9 mm, type 0-IIc, tub1, pT1a(M), ly0, v0, HM(-), VM(-)]. Two months after ESD, radiation therapy was started for the EC, and an almost complete response was obtained. Nine months after the ESD, a follow-up EGD showed a submucosal tumor-like lesion with ulceration, located immediately under the post-ESD scar, and biopsy specimens showed moderately differentiated SCC. There were no similar lesions suggesting hematogenous or lymphatic metastasis in the stomach. PMID:26973424

  15. Occult esophageal squamous cell carcinoma with metastases to the spine and central nervous system

    PubMed Central

    Roballo, Carla Adriane; de Campos, Pompeu Tomé Ribeiro; Teixeira, Carlos Osvaldo; Teixeira, Maria Aparecida Barone

    2015-01-01

    Esophageal malignancy encompasses a group of diseases that are mostly represented by the squamous cell carcinoma and the adenocarcinoma. Quite frequently, these neoplasms present aggressive behavior; therefore, the diagnosis is often made when the condition is in advanced stages. Dysphagia is the typical clinical complaint, although it is present only when most of the lumen is obstructed. Therefore, quite often, the metastatic disease is first diagnosed, which contributes to the patient's poor survival expectancy. The authors report the case of a 58-year-old man who looked for medical care complaining of a long-term history of scapular pain. The diagnostic work-up disclosed a cervical spine lytic lesion surrounded by a tumoral mass shown by computed tomography. The cervical tumor was sampled by fine needle aspiration, revealing an undifferentiated carcinoma. The outcome was unfavorable and the patient died. The autopsy findings revealed metastatic disease to the spine and central nervous system, and the primary tumor was found to be an esophageal squamous cell carcinoma, which had progressed without typical dysphagia. PMID:26484322

  16. Congenital esophageal stenosis owing to tracheobronchial remnants

    PubMed Central

    Rebelo, Priscila Guyt; Ormonde, João Victor C.; Ormonde, João Baptista C.

    2013-01-01

    OBJECTIVE To emphasize the need of an accurate diagnosis of congenital esophageal stenosis due to tracheobronchial remnants, since its treatment differs from other types of congenital narrowing. CASE DESCRIPTION Four cases of lower congenital esophageal stenosis due to tracheobronchial remnants, whose definitive diagnosis was made by histopathology. Except for the last case, in which a concomitant anti-reflux surgery was not performed, all had a favorable outcome after resection and anastomosis of the esophagus. COMMENTS The congenital esophageal stenosis is an intrinsic narrowing of the organâ€(tm)s wall associated with its structural malformation. The condition can be caused by tracheobronchial remnants, fibromuscular stenosis or membranous diaphragm and the first symptom is dysphagia after the introduction of solid food in the diet. The first-choice treatment to tracheobronchial remnants cases is the surgical resection and end-to-end anastomosis of the esophagus. PMID:24142326

  17. [Esophageal melanoma: report of two cases].

    PubMed

    Butte, Jean M; Visscher, Alvaro; DE LA Fuente, Hernán; Meneses, Manuel; Carrasco, Ana María; Amaral, Horacio; Waugh, Enrique

    2010-01-01

    Esophageal melanomas correspond to 0.1 to 0.2% of esophageal tumors. We report two patients with the disease. The first patient is a 51 year-old woman pre-sentingwith dysphagia and weight loss. An upper gastrointestinal endoscopy showed a polypoid ulcerated lesion in the middle third of the esophagus. The pathological study ofthe biopsy disclosed a malignant melanoma. The patient was subjected to an esophagectomy with a satisfactory postoperative evolution. Four months later, liver metastases were detected and the patient died eleven months after the operation. The second patient is a 59 year-old mole that consulted by dysphagia. An endoscopy showed a pigmented esophageal lesion whose pathological diagnosis was a malignant melanoma. The patient was subjected to an esophagectomy and sixteen months after surgery there was no evidence of relapse. PMID:20361155

  18. Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma

    PubMed Central

    Hyland, Paula L.

    2013-01-01

    In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal adenocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag single-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpathways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations. PMID:23358850

  19. An Overview of the Diagnosis and Management of Eosinophilic Esophagitis

    PubMed Central

    Singla, Manish B; Moawad, Fouad J

    2016-01-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the esophageal mucosa. The diagnosis requires esophageal biopsies demonstrating at least 15 eosinophils per high-powered field following a course of high-dose proton pump inhibitors. Management of EoE consists of the three Ds: drugs, dietary therapy, and esophageal dilation. In this review, we discuss the epidemiology, pathogenesis, diagnosis, and treatment of EoE to include the role of emerging therapies. PMID:26986655

  20. Inactivation of GSK3β and activation of NF-κB pathway via Axl represents an important mediator of tumorigenesis in esophageal squamous cell carcinoma.

    PubMed

    Paccez, Juliano D; Duncan, Kristal; Vava, Akhona; Correa, Ricardo G; Libermann, Towia A; Parker, M Iqbal; Zerbini, Luiz F

    2015-03-01

    The receptor tyrosine kinase Axl has been described as an oncogene, and its deregulation has been implicated in the progression of several human cancers. While the role of Axl in esophageal adenocarcinoma has been addressed, there is no information about its role in esophageal squamous cell carcinoma (OSCC). In the current report, we identified, for the first time, deregulation of Axl expression in OSCC. Axl is consistently overexpressed in OSCC cell lines and human tumor samples, mainly in advanced stages of the disease. Blockage of Axl gene expression by small interfering RNA inhibits cell survival, proliferation, migration, and invasion in vitro and esophageal tumor growth in vivo. Additionally, repression of Axl expression results in Akt-dependent inhibition of pivotal genes involved in the nuclear factor-kappaB (NF-κB) pathway and in the induction of glycogen synthase kinase 3β (GSK3β) activity, resulting in loss of mesenchymal markers and induction of epithelial markers. Furthermore, treatment of esophageal cancer cells with the Akt inhibitor wortmannin inhibits NF-κB signaling, induces GSK3β activity, and blocks OSCC cell proliferation in an Axl-dependent manner. Taken together, our results establish a clear role for Axl in OSCC tumorigenesis with potential therapeutic implications. PMID:25568334

  1. Systematic review: Eosinophilic esophagitis in Asian countries

    PubMed Central

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Oshima, Naoki; Ishihara, Shunji

    2015-01-01

    AIM: To investigate the prevalence and the clinical characteristics of Asian patients with eosinophilic esophagitis. METHODS: We conducted a systematic search of the PubMed and Web of Science databases for original studies, case series, and individual case reports of eosinophilic esophagitis in Asian countries published from January 1980 to January 2015. We found 66 and 80 articles in the PubMed and Web of Science databases, respectively; 24 duplicate articles were removed. After excluding animal studies, articles not written in English, and meeting abstracts, 25 articles containing 217 patients were selected for analysis. RESULTS: Sample size-weighted mean values were determined for all pooled prevalence data and clinical characteristics. The mean age of the adult patients with eosinophilic esophagitis was approximately 50 years, and 73% of these patients were male. They frequently presented with allergic diseases including bronchial asthma, allergic rhinitis, food allergy, and atopic dermatitis. Bronchial asthma was the most frequent comorbid allergic disease, occurring in 24% of patients with eosinophilic esophagitis. Dysphagia was the primary symptom reported; 44% of the patients complained of dysphagia. Although laboratory blood tests are not adequately sensitive for an accurate diagnosis of eosinophilic esophagitis, endoscopic examinations revealed abnormal findings typical of this disease, including longitudinal furrows and concentric rings, in 82% of the cases. One-third of the cases responded to proton pump inhibitor administration. CONCLUSION: The characteristics of eosinophilic esophagitis in Asian patients were similar to those reported in Western patients, indicating that this disease displays a similar pathogenesis between Western and Asian patients. PMID:26217096

  2. Esophageal recurrence of medullary thyroid carcinoma

    PubMed Central

    Dworzynska, Agnieszka; Lorente-Poch, Leyre; Sancho, Juan Jose; Sitges-Serra, Antonio

    2015-01-01

    Medullary thyroid carcinoma (MTC) metastasizes to the regional lymph nodes and to the lungs, liver and bones. Only one case of recurrence of MTC involving the upper gastrointestinal tract has been reported so far. We describe the case of a 38-year-old woman with MTC, who developed an upper esophageal submucosal recurrence after two previous local recurrences treated surgically and one ethanol injection. After resection of the right lateral esophageal wall, calcitonin dropped by 60% and showed a doubling time >1 year. We cannot rule out the role of deep ethanol injection in the involvement of the cervical esophagus wall. PMID:26645011

  3. MicroRNAs and esophageal cancer

    PubMed Central

    Patnaik, Santosh Kumar; Mallick, Reema

    2010-01-01

    Cancer of the esophagus is a highly aggressive disease associated with an overall poor prognosis. There is an insistent need for improving our understanding of the molecular basis of this disease. The recent emergence of observations on the role of microRNAs in cancer and their potential as biomarkers has prompted many investigations to examine their relevance to esophageal cancer. This article provides an introduction to microRNA biology and the techniques involved in studying them, and summates what is now known about their role and utility in regard to neoplastic esophageal diseases. PMID:22811805

  4. Eosinophilic esophagitis in adults: An update

    PubMed Central

    Ahmed, Monjur

    2016-01-01

    Eosinophilic esophagitis is a worldwide chronic allergic disease of the esophagus. In the last decade, there is an epidemic of this entity in the western world. Mostly seen in children and young adults, patients present with dysphagia or food impaction in the emergency room. Characteristic endoscopic findings, esophageal eosinophilia and non-responsiveness to proton pump inhibitors help make the diagnosis. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the esophagus are the mainstays of treatment. Investigations are ongoing for mucosal healing and optimum maintenance treatment. PMID:27158535

  5. Eosinophilic esophagitis in adults: An update.

    PubMed

    Ahmed, Monjur

    2016-05-01

    Eosinophilic esophagitis is a worldwide chronic allergic disease of the esophagus. In the last decade, there is an epidemic of this entity in the western world. Mostly seen in children and young adults, patients present with dysphagia or food impaction in the emergency room. Characteristic endoscopic findings, esophageal eosinophilia and non-responsiveness to proton pump inhibitors help make the diagnosis. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the esophagus are the mainstays of treatment. Investigations are ongoing for mucosal healing and optimum maintenance treatment. PMID:27158535

  6. Immunologic function of dendritic cells in esophageal cancer.

    PubMed

    Yang, Wenfeng; Yu, Jinming

    2008-07-01

    Esophageal cancer is one of the frequently occurring malignant cancers. The current therapy, including surgery, chemotherapy, radiotherapy, or a combination, is only to palliate the symptoms; overall the prognosis is poor. The immunotherapy of dendritic cells for esophageal cancer is a valuable method. Dendritic cells existing in the esophageal tissues play an important role in the host's immunosurveillance against cancer as the professional antigen-presenting cells. This review concerns the immunology of dendritic cells in esophageal cancer; it describes the expression of DCs in the normal esophageal tissues and benign disease of esophagus, relations between the DCs and cancer development in esophageal cancer, and the DC-based approach to establish treatment for esophageal cancer. PMID:18080193

  7. The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma

    PubMed Central

    Shi, Xuefei; Yao, Yanwen; Yang, Wen; Song, Yong

    2015-01-01

    Long noncoding RNAs (lncRNAs) have emerged as key regulators of tumor development and progression. The lncRNA HNF1A-antisense 1 (HNF1A-AS1) is a 2455-bp transcript on chromosome 12 with a potential oncogenic role in esophageal adenocarcinoma. Nevertheless, current understanding of the involvement of HNF1A-AS1 in lung adenocarcinoma tumorigenesis remains limited. In this study, we analyzed the roles of HNF1A-AS1 in 40 lung adenocarcinoma tissues and five lung cancer cell lines. Our results showed that HNF1A-AS1 was significantly up-regulated in lung adenocarcinoma tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with TNM stage, tumor size, and lymph node metastasis. The UCSC Cancer Genomics Browser's Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup. Moreover, HNF1A-AS1 was determined to promote tumor proliferation and metastasis, both in vitro and in vivo, by regulating cyclin D1, E-cadherin, N-cadherin and β-catenin expression. In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin. In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma. PMID:25863539

  8. [Medium-term outcome, follow-up, and quality of life in children treated for type III esophageal atresia].

    PubMed

    Lepeytre, C; De Lagausie, P; Merrot, T; Baumstarck, K; Oudyi, M; Dubus, J-C

    2013-10-01

    The aim of this study was to evaluate the medium-term outcome (health status, medical and surgical French National Health Authority-recommended follow-up, and quality of life) of children born with type III esophageal atresia (EA). Previous events (during the perinatal period, associated abnormalities, respiratory and digestive complications) of children treated for type III EA at the Marseille university hospitals between 1999 and 2009 were noted. Parents completed a standardized questionnaire concerning the health of their children during the previous year, and a quality-of-life questionnaire (PedsQL 4.0) was also completed by children aged more than 8 years. Among the 68 children treated, 44 responded to our solicitation (mean age, 7.6 years; range, 3-12.8 years). Previous important events were : pneumonia(s) (65%), asthma before the age of 3 years (66%), hospitalization for a respiratory event (45%), fundoplication (20%), and esophageal dilatation (45%). We noted current chronic cough (16%), asthma (30%), dysphagia (39%), and symptomatic gastroesophageal reflux (9%). National guidelines were not respected, except for the surgical indications in children aged less than 6 years. The quality-of-life scores (n=43 children) were similar to healthy controls but were negatively influenced by a gastrostomy procedure (P=0.020), pneumonia (P=0.013), and hospitalization due to a respiratory event (P=0.006) or a digestive event (P=0.010), and also by current asthma (P=0.004). In conclusion, despite recurrent respiratory or digestive symptoms and inadequate recommended follow-up, the quality of life of children treated for type III of EA is good. PMID:23932659

  9. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... message was transmitted. The message shall be in the primary language of the EAS Participant and be fully... input. (8) Decoder Programming. Access to decoder programming shall be protected by a lock or...

  10. The system of EAS time analysis

    NASA Technical Reports Server (NTRS)

    Khalafyan, A. Z.; Mkhitaryan, V. M.; Oganezova, J. S.; Bashindjaghayan, G. L.; Sinev, N. B.; Sarycheva, L. I.

    1985-01-01

    The extensive air showers' (EAS) front shape, angle of incidence, disk thickness, particle distribution along the shower, on the delayed and EAS front advancing particles were determined. The suggested system of the EAS time analysis allows determination of the whole EAS longitudinal structure at the observation points. The information from the detectors is continuously recorded in the memory with the memory cell switching in 5 ns, this enables fixation of the moment of pulse input from the detector with an accuracy to + or - 2.5 ns. Along with the fast memory, a slow memory with the cell switching in 1 micron s is introduced in the system, this permits observation of relatively large time intervals with respect to the trigger pulse with an appropriately lower accuracy.

  11. Acute Herpes Simplex Viral Esophagitis Occurring in 5 Immunocompetent Individuals With Eosinophilic Esophagitis

    PubMed Central

    Criblez, Dominique H.; Dellon, Evan S.; Bussmann, Christian; Pfeifer, David; Froh, Matthias; Straumann, Alex

    2016-01-01

    Herpes simplex esophagitis (HSE) is an acute, severe viral infection of the esophagus, rarely occurring in immunocompetent individuals. Eosinophilic esophagitis (EoE) is a rare immune-mediated esophageal disorder. We recently observed 5 severe HSE cases in diagnosed EoE patients. Four of the 5 patients had active, untreated EoE at the time of infection, so HSE is not likely a side effect of swallowed topical corticosteroids, the first-line medical treatment of EoE. However, this coincidence of these 2 rare conditions raises the question of a causal relationship between these 2 forms of esophagitis, and whether active EoE might predispose to HSE infection. PMID:27144193

  12. Acute Herpes Simplex Viral Esophagitis Occurring in 5 Immunocompetent Individuals With Eosinophilic Esophagitis.

    PubMed

    Zimmermann, Dorothee; Criblez, Dominique H; Dellon, Evan S; Bussmann, Christian; Pfeifer, David; Froh, Matthias; Straumann, Alex

    2016-04-01

    Herpes simplex esophagitis (HSE) is an acute, severe viral infection of the esophagus, rarely occurring in immunocompetent individuals. Eosinophilic esophagitis (EoE) is a rare immune-mediated esophageal disorder. We recently observed 5 severe HSE cases in diagnosed EoE patients. Four of the 5 patients had active, untreated EoE at the time of infection, so HSE is not likely a side effect of swallowed topical corticosteroids, the first-line medical treatment of EoE. However, this coincidence of these 2 rare conditions raises the question of a causal relationship between these 2 forms of esophagitis, and whether active EoE might predispose to HSE infection. PMID:27144193

  13. Prognostic and predictive markers in pancreatic adenocarcinoma.

    PubMed

    Le, Nha; Sund, Malin; Vinci, Alessio

    2016-03-01

    Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracil-leucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant. PMID:26769569

  14. Outpatient management of esophageal cancer with endoscopic Nd:YAG laser.

    PubMed

    Lightdale, C J; Zimbalist, E; Winawer, S J

    1987-01-01

    In 50 inoperable patients with advanced malignant obstruction of the esophagus, endoscopic Nd:YAG laser treatment was used for palliation of dysphagia. In 30 of these patients, treatment was carried out entirely in an outpatient setting, providing more time at home and saving costs of hospitalization. Most patients had received prior radiation and chemotherapy. All were unable to swallow solid food; 16 had difficulty with liquids. Palliation was achieved in 69% allowing patients to eat a nearly normal diet. Therapy was least successful in cancers involving the cervical esophagus, in cancers more than 8 cm in length, and in cancers that were primarily infiltrating or extraluminal. Epidermoid carcinomas and adenocarcinomas were effectively treated, except for adenocarcinomas of the gastric cardia, which tended to be infiltrating. There were two serious but nonfatal complications, one perforation and one episode of bleeding, directly attributable to Nd:YAG laser therapy. An esophageal dilation prior to endoscopic Nd:YAG laser treatment facilitated outpatient management. PMID:2432776

  15. Catumaxomab for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas

    ClinicalTrials.gov

    2015-11-16

    Gastric Adenocarcinoma With Peritoneal Carcinomatosis; Siewert Type II Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis; Siewert Type III Adenocarcinoma of Esophagogastric Junction With Peritoneal Carcinomatosis

  16. [Esophageal perforation following a biopsy in a patient with eosinophilic esophagitis].

    PubMed

    Benítez Cantero, José Manuel; Angel Rey, José Manuel; Rodríguez Perálvarez, Manuel; Ayllón Terán, María Dolores; Jurado García, Juan; Soto Escribano, Pilar; Hervás Molina, Antonio José; Poyato González, Antonio; González Galilea, Angel

    2011-01-01

    Eosinophilic esophagitis is an underdiagnosed disease that should be suspected in all patients with dysphagia and food impaction. Although these are the leading symptoms, the clinical and endoscopic spectrum is highly varied. Clinicians should be aware of the risk of endoscopy-related complications in this disorder. Precautions should be maximized in endoscopic examinations to avoid iatrogenic damage. We describe the case of a young patient with esophageal stricture and dysphagia who suffered a perforation following a biopsy. PMID:21703721

  17. Esophageal Granular Cell Tumor and Eosinophilic Esophagitis: Two Interesting Entities Identified in the Same Patient

    PubMed Central

    Lucendo, Alfredo J.; De Rezende, Livia; Martín-Plaza, Jesús; Larrauri, Javier

    2008-01-01

    We illustrate the case of a 41-year-old male with allergic manifestations since childhood. He sought medical attention for intermittent, progressive dysphagia from which he had been suffering for a number of years, having felt the sensation of a retrosternal lump and a self-limited obstruction to the passage of food. Endoscopy detected a submucosal tumor in the upper third of the esophagus, which was typified, via biopsy, as a granular cell tumor with benign characteristics and probably responsible for the symptoms. Two years later, the patient sought medical attention once again as these symptoms had not abated, hence digestive endoscopy was repeated. This revealed stenosis of the junction between the middle and lower thirds of the organ which had not been detected previously but was passable under gentle pressure. Eosinophilic esophagitis was detected after biopsies were taken. Esophageal manometry identified a motor disorder affecting the esophageal body. Following three months of treatment using fluticasone propionate applied topically, the symptoms went into remission, esophageal stenosis disappeared and the esophageal biopsies returned to normal. This is the first documented case of the link between granular cell tumors and Eosinophilic esophagitis, two different disorders which could cause dysphagia in young patients. PMID:21490835

  18. Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma.

    PubMed

    Chen, Tiantian; Cheng, Hongwei; Chen, Xingdong; Yuan, Ziyu; Yang, Xiaorong; Zhuang, Maoqiang; Lu, Ming; Jin, Li; Ye, Weimin

    2015-01-01

    A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42-2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74-36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54-2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

  19. A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma

    SciTech Connect

    Czito, Brian G. . E-mail: czito@radonc.duke.edu; Kelsey, Chris R.; Hurwitz, Herbert I.; Willett, Chris G.; Morse, Michael A.; Blobe, Gerard C.; Fernando, Nishan H.; D'Amico, Thomas A.; Harpole, David H.; Honeycutt, Wanda R.N.; Yu Daohai; Bendell, Johanna C.

    2007-03-15

    Purpose: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is undefined. We evaluated a combination of capecitabine, carboplatin, and paclitaxel with RT in a phase I study. Methods and Materials: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received capecitabine, carboplatin, and paclitaxel with RT (1.8 Gy daily to 50.4 Gy). After completion, patients were restaged and evaluated for surgery. Primary endpoints included determination of dose-limiting toxicities (DLT) and a recommended phase II dose, non-DLT, and preliminary radiographic and pathologic response rates. Results: Thirteen patients were enrolled (10 men, 3 women). All were evaluable for toxicity and efficacy. Two of 3 patients at dose level 1 (capecitabine 825 mg/m{sup 2} twice daily on RT days, carboplatin area under the curve (AUC) 2 weekly, paclitaxel 60 mg/m{sup 2} weekly) had DLT (both Grade 4 esophagitis). Of these 3, 2 underwent esophagectomy and had pathologic complete response (pCR). Ten patients were then enrolled at dose level -1 (capecitabine 600 mg/m{sup 2} twice daily, carboplatin AUC 1.5, paclitaxel 45 mg/m{sup 2}). Overall, 3 of 10 patients at dose level -1 developed DLT (2 Grade 3 esophagitis, 1 Grade 3 hypotension). Esophagectomy was performed in 6 of 10 patients. All patients had pathologic downstaging and 2 of 6 had pCR. Conclusions: The maximally tolerated/recommended phase II doses were capecitabine 600 mg/m{sup 2} twice daily, carboplatin AUC 1.5 weekly, and paclitaxel 45 mg/m{sup 2} weekly with RT to 50.4 Gy. In our small study, this regimen appears active but is accompanied by significant toxicities, primarily esophagitis.

  20. Imaging preoperatively for pancreatic adenocarcinoma

    PubMed Central

    Pietryga, Jason Alan

    2015-01-01

    Pancreatic cancer is a highly lethal malignancy which is increasing in incidence and mortality. The fourth leading cause of cancer death in the U.S., pancreatic cancer is projected to become the second leading cause of cancer death by 2020. Patients with pancreatic cancer have an abysmal 5-year survival of 6%, and 90% of these patients eventually die from the disease. This is in large part due to the commonly advanced stage of disease at the time of diagnosis. Currently, the only potentially curative therapy for pancreatic carcinoma is complete surgical resection. Patients who undergo incomplete resection with residual disease have similar survival rates to those patients with metastatic disease and should be spared this relatively morbid surgery. Thus, the key to impacting prognosis is the detection of smaller and earlier stage lesions, and the key to optimal management is accurately determining which patients have potentially resectable surgery and which patients would not benefit from surgery. Cross-sectional imaging plays an essential role in both the diagnosis and appropriate staging of pancreatic carcinoma. The diagnosis and staging of pancreatic adenocarcinoma is performed with cross-sectional imaging. Multi-detector computed tomography (MDCT) is the most commonly used, best-validated imaging modality for the diagnosis and staging of pancreatic cancer. Modern contrast-enhanced magnetic resonance imaging (MRI) has been demonstrated to be equivalent to MDCT in detection and staging of pancreatic cancer. Endoscopic ultrasound (EUS) is very sensitive for detecting pancreatic masses; however, due to limitations in adequate overall abdominal staging, it is generally used in addition to or after MDCT. Transabdominal ultrasound and positron emission tomography/computed tomography (PET/CT) have limited roles in the diagnosis and staging of pancreatic cancer. Preoperative imaging is used to characterize patients as having resectable disease, borderline resectable disease, locally advanced disease (unresectable) and metastatic disease (unresectable). As the definitions of borderline resectable and unresectable may vary from institution to institution and within institutions, it is essential to accurately assess and describe the factors relevant to staging including: local extent of tumor, vascular involvement, lymph node involvement and distant metastatic disease. To facilitate this, standardized reporting templates for pancreatic ductal adenocarcinoma have been created and published. Structured reporting for pancreatic cancer has been reported to provide superior evaluation of pancreatic cancer, facilitate surgical planning, and increase surgeons confidence about tumor resectability. PMID:26261722

  1. Acute esophageal necrosis caused by alcohol abuse

    PubMed Central

    Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

    2005-01-01

    Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

  2. A safe treatment option for esophageal bezoars

    PubMed Central

    Yaqub, Sheraz; Shafique, Muhammad; Kjæstad, Erik; Thorsen, Yngve; Lie, Erik S.; Dahl, Vegard; Bakka, Njål; Røkke, Ola

    2012-01-01

    INTRODUCTION Bezoar in the esophagus is a rare condition and associated with structural or functional abnormalities of the esophagus. Endoscopy is the main tool for diagnosis and treatment for bezoar in the esophagus. PRESENTATION OF CASE Here we present a case where an endoscopic evacuation of an esophageal bezoar was unsuccessful. We treated the bezoar through a nasogastric tube using a cocktail composed of pancreatic enzymes dissolved in Coca-Cola. DISCUSSION Endoscopy is regarded as the mainstay for the diagnosis and treatment of esophageal bezoars. However, when this approach fails, other treatment options include dissolution therapy, and surgical exploration and removal of the bezoar. Surgical removal of an esophageal bezoar is associated with a high risk of morbidity and mortality. We advocate that dissolving therapy should be the first choice of treatment when endoscopic evacuation is not possible. CONCLUSION This is the first report describing a successful treatment of an esophageal bezoar with a cocktail of Coca-Cola and pancreatic enzymes. It is an effective, inexpensive, and worldwide available treatment and should be considered when endoscopic evacuation fails. PMID:22609703

  3. Esophageal testing: What we have so far.

    PubMed

    de Bortoli, Nicola; Martinucci, Irene; Bertani, Lorenzo; Russo, Salvatore; Franchi, Riccardo; Furnari, Manuele; Tolone, Salvatore; Bodini, Giorgia; Bolognesi, Valeria; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino; Savarino, Edoardo Vincenzo

    2016-02-15

    Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising. PMID:26909230

  4. Current Management of Eosinophilic Esophagitis 2015.

    PubMed

    Richter, Joel E

    2016-02-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by esophageal dysfunction and eosinophilic infiltrate (≥15/hpf) in the esophageal epithelium and the absence of other potential causes of eosinophilia. The prevalence is increasing and is the most common cause of solid food dysphagia in children and young adults. This article will review the diagnosis and management of EoE based on consensus conferences, systematic reviews, and meta-analysis and highlights seminal studies in our evolving treatment of this disease. However, all answers are not available and I will remark about the lessons learned in my clinical practice seeing EoE patients over the last 25 years. The complicated etiology of the complaint of dysphagia in EoE patients will be reviewed. The importance of utilizing endoscopy, biopsies, and barium esophagram to help define the 2 phenotypes (inflammatory, fibrostenosis) of EoE will be highlighted. The controversy about PPI-responsive esophageal eosinophilia will be discussed and contrasted with idiopathic EoE. Finally, the 3 treatment options for EoE (drugs, diet, dilation) will be reviewed in detail and a useful clinical management algorithm presented. PMID:26485101

  5. Esophageal testing: What we have so far

    PubMed Central

    de Bortoli, Nicola; Martinucci, Irene; Bertani, Lorenzo; Russo, Salvatore; Franchi, Riccardo; Furnari, Manuele; Tolone, Salvatore; Bodini, Giorgia; Bolognesi, Valeria; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino; Savarino, Edoardo Vincenzo

    2016-01-01

    Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising. PMID:26909230

  6. Histomorphological and Immunophenotypic Features of Pill-Induced Esophagitis

    PubMed Central

    Kim, Su Hwan; Kim, Won; Lee, Kook Lae; Byeon, Sun-ju; Choi, Euno; Chang, Mee Soo

    2015-01-01

    The aim of this study was to investigate histomorphological and immunophenotypic features in pill-induced esophagitis. We comparatively evaluated the histomorphological, immunophenotypic features of pill-induced esophagitis vs. reflux esophagitis, as well as clinical information and endoscopic findings. Fifty-two tissue pieces from 22 cases of pill-induced esophagitis, 46 pieces from 20 reflux esophagitis, and 16 pieces from 14 control samples were subjected to immunohistochemistry for inflammatory infiltrates (CD3 for T lymphocyte, CD20 for B lymphocyte, CD56 for NK cell, CD68 for macrophage, CD117 for mast cell) and eosinophil chemotaxis-associated proteins (Erk, leptin, leptin receptor, pSTAT3, phospho-mTOR). As a result, Histomorphology showed that a diffuse pattern of dilated intercellular spaces was more frequently observed in pill-induced esophagitis, while reactive atypia and subepithelial papillary elongation were more often found in reflux esophagitis (P < 0.05, respectively). Interestingly, intraepithelial eosinophilic microabscess, intraepithelial pustule and diffuse pattern of dilated intercellular spaces were observed in 14% (3 cases), 9% (2 cases) and 32% (7 cases) of pill-induced esophagitis, respectively, but in no cases of reflux esophagitis. Regarding intraepithelial inflammatory infiltrates in pill-induced esophagitis, T lymphocytes were the most common cells, followed by eosinophil; 11 and 7 in one x400 power field, respectively. Intraepithelial pSTAT3-positive pattern was more frequently observed in pill-induced esophagitis than in reflux esophagitis, at 45% (10 cases) versus 10% (2 cases), respectively (P < 0.05). Considering the distal esophageal lesion only, intraepithelial pustule, diffuse dilated intercellular spaces and stromal macrophages were more frequently found in distal pill-induced esophagitis, whereas reactive atypia and intraepithelial mast cells in reflux esophagitis (P < 0.05, respectively). In conclusion, diffuse dilated intercellular spaces, intraepithelial eosinophil microabscess, pustule, T lymphocytes, eosinophils, and pSTAT3 positivity can be added to histopathological features of pill-induced esophagitis, other than non-specific ulcer. Besides, distal pill-induced esophagitis may be histopathologically differentiated from reflux esophagitis. PMID:26047496

  7. Mimics of pancreatic ductal adenocarcinoma

    PubMed Central

    Kaza, Ravi K.; Azar, Shadi F.; Ruma, Julie A.; Francis, Isaac R.

    2013-01-01

    Abstract Several uncommon primary pancreatic tumors, inflammatory conditions, metastasis to the pancreas and peripancreatic masses can mimic the appearance of pancreatic ductal adenocarcinoma (PDA). Differentiation between these lesions and PDA can be challenging, due to the overlap in imaging features; however, familiarity with their typical imaging features and clinical presentation may be helpful in their differentiation, as in some cases, invasive diagnostic tests or unnecessary surgery can be avoided. The different pathologies that can mimic PDA include inflammatory conditions such as the various forms of pancreatitis (chronic-focal mass-forming, autoimmune and groove pancreatitis), pancreatic neuroendocrine tumors, solid pseudopapillary tumors, metastasis (solid non-lymphomatous and hematologic), congenital variants (annular pancreas), as well as peripancreatic lesions (accessory spleen, adrenal masses, duodenal masses, lymph nodes and vascular lesions), and certain rare pancreatic tumors (e.g., acinar cell tumors, solid serous tumors, hamartoma and solitary fibrous tumors). The clinical presentation and imaging features of the most commonly encountered mimics of PDA are discussed in this presentation with representative illustrations. PMID:24060833

  8. Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor

    PubMed Central

    Feng, Fan; Tian, Yangzi; Liu, Zhen; Xu, Guanghui; Liu, Shushang; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    Abstract Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis. Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center. The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs. The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs. PMID:26765432

  9. Oesophageal adenocarcinoma: the new epidemic in men?

    PubMed

    Rutegård, Martin; Lagergren, Pernilla; Nordenstedt, Helena; Lagergren, Jesper

    2011-07-01

    The last decades have witnessed an unprecedented rise in the incidence of oesophageal adenocarcinoma. This rise has mainly affected men, and current male-to-female sex ratio estimates range from 7-10 to 1. Major risk factors for oesophageal adenocarcinoma are gastro-oesophageal reflux disease and obesity, especially in combination. The prevalence of these risk factors has increased during the last decades, but there does not seem to be a marked differential distribution among men and women. However, reflux among men is more often associated with erosive reflux disease than it is among women. There is also evidence that male-type obesity, with a prominent abdominal distribution of fat, confers a greater risk increase for oesophageal adenocarcinoma than the female equivalent. Due to the marked male predominance and the finding that women tend to develop specialized intestinal metaplasia (Barrett's oesophagus) and adenocarcinoma at a later age than men, interest has been directed towards a potential aetiological role of reproductive factors and sex hormones. Breastfeeding has been found to be a protective factor for the development of adenocarcinoma, while no association has hitherto been established with other reproductive factors. Taken together, the male predominance in the incidence of oesophageal adenocarcinoma may partly be explained by the differential effect of the major risk factors reflux disease and obesity, but the mechanisms whereby this occurs need to be elucidated. Moreover, the association with breastfeeding indicates a need for extensive epidemiological studies to clarify a possible role of sex hormonal influence in the aetiology of oesophageal adenocarcinoma. PMID:21602001

  10. Phase I evaluation of TNFerade biologic plus chemoradiotherapy before esophagectomy for locally advanced resectable esophageal cancer

    PubMed Central

    Chang, Kenneth J.; Reid, Tony; Senzer, Neil; Swisher, Stephen; Pinto, Harlan; Hanna, Nader; Chak, Amitabh; Soetikno, Roy

    2015-01-01

    Background Neoadjuvant chemoradiotherapy followed by surgery is the primary treatment option for patients with locally advanced esophageal cancer. This multicenter phase I trial examined intratumoral injection of TNFerade biologic, an adenoviral vector that expresses the human tumor necrosis factor-α gene, with chemoradiotherapy in locally advanced esophageal cancer. Objectives To assess pathologic complete response (pCR), time to disease progression, progression-free survival, survival, and safety and tolerance in patients treated with preoperative chemoradiation combined with endoscopy or EUS-guided intratumoral injection of TNFerade biologic. Design/Intervention Five weekly injections of TNFerade biologic, dose-escalated logarithmically from 4 × 108 to 4 × 1011 particle units (PU), were given in combination with cisplatin 75 mg/m2 and intravenous 5-fluorouracil 1000 mg/m2/d for 96 hours on days 1 and 29, and concurrent radiation therapy to 45 Gy. Surgery was performed 9 to 15 weeks after treatment. Setting U.S. multicenter study. Patients Patients with stage II and III esophageal cancer were enrolled. Main Outcome Measurements Primary outcome measures were safety, feasibility, tolerability, and rate of pCR. Secondary outcome measures were overall survival (OS) and disease-free survival. Results Twenty-four patients with a median age of 61 years were enrolled; 88% of the patients were men, 21% were stage II, and 79% were stage III. Six (29%) had a pCR, observed among 21 patients (20 who underwent esophagectomy and 1 at autopsy). Dose-limiting toxicities were not observed. The most frequent potentially related adverse events were fatigue (54%), fever (38%), nausea (29%), vomiting (21%), esophagitis (21%), and chills (21%). At the top dose of 4 × 1011 PU, thromboembolic events developed in 5 of 8 patients. The median OS was 47.8 months. The 3-and 5-year OS rates and disease-free survival rates were 54% and 41% and 38% and 38%, respectively. Limitations We included primarily adenocarcinoma. Conclusions Preoperative TNFerade, in combination with chemoradiotherapy, is active and safe at doses up to 4 × 1010 PU and is associated with long survival. This regimen warrants additional studies. (Clinical trial registration number: NCT00051480.) PMID:22520270

  11. A striking local esophageal cytokine expression profile in eosinophilic esophagitis1

    PubMed Central

    Blanchard, Carine; Stucke, Emily M.; Rodriguez-Jimenez, Beatriz; Burwinkel, Karen; Collins, Margaret H.; Ahrens, Annette; Alexander, Eileen S.; Butz, Bridget K. Buckmeier; Jameson, Sean C.; Kaul, Ajay; Franciosi, James P.; Kushner, Jonathan P.; Putnam, Philip E.; Abonia, J. Pablo; Rothenberg, Marc E.

    2011-01-01

    Background Eosinophilic esophagitis (EE) is an emerging worldwide disease that mimics gastroesophageal reflux disease. Objective Early studies have suggested that esophageal eosinophilia occurs in association with T helper type 2 allergic responses, yet the local and systemic expression of relevant cytokines has not been well characterized. Methods A human inflammatory cytokine and receptor PCR array containing 84 genes followed by PCR validation and multiplex arrays were used to quantify cytokine mRNA in esophageal biopsies and blood levels. Results Esophageal transcripts of numerous chemokines [e.g. CCL1, CCL23, CCL26 (eotaxin-3), CXCL1, and CXCL2], cytokines (e.g. IL13 and ABCF1), and cytokine receptors (e.g. IL5RA) were induced at least 4-fold in individuals with EE. Analysis of esophageal biopsies (n=288) revealed that eotaxin-3 mRNA level alone had 89% sensitivity for distinguishing EE from non-EE individuals. The presence of allergy was associated with significantly increased esophageal expression of IL4 and IL5 mRNA in active EE patients. We identified 8 cytokines (IL-4, IL-13, IL-5, IL-6, IL-12p70, CD40L, IL-1α, and IL-17) whose blood levels retrospectively distinguished 12 non-EE from 13 EE patients with 100% specificity and 100% sensitivity. When applied to a blinded, prospectively recruited group of 36 patients, the cytokine panel scoring system had a 79% positive predictive value, 68% negative predictive value, 61% sensitivity, and 83% specificity for identifying EE. Conclusion Evidence is presented that IL13 and IL5 associate with eosinophil and eotaxin-3 levels, indicating the key role of adaptive Th2 immunity in regulating eotaxin-3-driven esophageal eosinophilia in the absence of a consistent systemic change in cytokines. PMID:21211656

  12. Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

    ClinicalTrials.gov

    2013-06-03

    Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

  13. Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esophageal carcinomas: a two-color flow-cytometric analysis.

    PubMed

    Koyama, S; Maruyama, T; Adachi, S

    1999-01-01

    Quantitative analysis based on the percentage of positive cells by two-color flow cytometry was used to quantify the surface expression of epidermal growth factor receptor (EGFR), and exons v6 and v9 of CD44 splice variants on tumor. Almost all patients with primary gastric and esophageal carcinomas, and benign mucosa of the stomach and esophagus showed usually high levels of EGFR expression, a mean of approximately 60% of cells being positive. Metastatic gastric carcinoma showed significantly higher levels of EGFR expression, a mean of 80% of cells being positive. Reduced expression of EGFR was observed in irradiated esophageal carcinoma. Adenocarcinomas, including primary and metastatic lesions, or cancer cell lines of the stomach revealed consistently very low or undetectable levels of expression of exon v6 of the CD44 variant (CD44v) protein. However, CD44v containing exon v9 could be detected in normal gastric epithelium and primary gastric carcinoma as well as in six adenocarcinoma cell lines. Exon v9 is significantly overexpressed on metastatic adenocarcinoma cells obtained from malignant ascites. On the other hand, normal squamous epithelium and primary squamous cell carcinoma (SCC) of the esophagus, and two SCC cell lines showed coexpression of exons v6 and v9 of CD44v. The expression of the CD44v6 molecule was significantly reduced in the irradiated primary SCC, although CD44v9 expression on the primary SCC remained unchanged after the radiation therapy. These results suggest that up-regulation of EGFR and CD44v9 molecules on gastric carcinomas, especially metastatic adenocarcinomas, shows tumor growth and tumor progression. In addition, down-regulation of EGFR and CD44v6 molecules on irradiated esophageal carcinoma may be involved in the mechanisms suppressing tumor growth and metastatic potential. PMID:10037277

  14. Detection of esophageal ulcerations with technetium-99m albumin sucralfate

    SciTech Connect

    Goff, J.S.; Adcock, K.A.; Schmelter, R.

    1986-07-01

    Technetium-99m albumin-sucralfate ((/sup 99m/Tc)Su) can be used to demonstrate peptic ulcer disease in man and animals. We evaluated the usefulness of (/sup 99m/Tc)Su for detecting various grades of esophagitis. (/sup 99m/Tc)Su adhered to the distal esophagus for up to 3 hr in five of six patients with esophageal ulcers but adhered to only two of nine with lesser degrees of esophagitis. No adherence was seen in five patients without esophagitis. Thus, (/sup 99m/Tc)Su may not be useful for detecting any but the most severe grade of esophagitis. Based on these results, we speculate that the previously documented beneficial effects of sucralfate on mild to moderate esophagitis may be due to other mechanisms besides adherence to the ulcerated mucosa.

  15. Risk factors for adenocarcinoma of the lung

    SciTech Connect

    Brownson, R.C.; Reif, J.S.; Keefe, T.J.; Ferguson, S.W.; Pritzl, J.A.

    1987-01-01

    The relation between various risk factors and adenocarcinoma of the lung was evaluated in a case-control study. Subjects were selected from the Colorado Central Cancer Registry from 1979-1982 in the Denver metropolitan area. A total of 102 (50 males and 52 females) adenocarcinoma case interviews and 131 (65 males and 66 females) control interviews were completed. The control group consisted of persons with cancers of the colon and bone marrow. The risk estimates associated with cigarette smoking were significantly elevated among males (odds ratio (OR) = 4.49) and females (OR = 3.95) and were found to increase significantly (p less than 0.01) with increasing levels of cigarette smoking for both males and females. For adenocarcinoma in females, the age- and smoking-adjusted odds ratios at different levels of passive smoke exposure followed an increasing overall trend (p = 0.05). After additional adjustment for potential confounders, prior cigarette use remained the most significant predictor of risk of adenocarcinoma among males and females. Analysis restricted to nonsmoking females revealed a risk of adenocarcinoma of 1.68 (95% confidence interval (Cl) = 0.39-2.97) for passive smoke exposure of four or more hours per day. Neither sex showed significantly elevated risk for occupational exposures, although males bordered on significance (OR = 2.23, 95% Cl = 0.97-5.12). The results suggest the need to develop cell type-specific etiologic hypotheses.

  16. A Phase II Study of a Paclitaxel-Based Chemoradiation Regimen With Selective Surgical Salvage for Resectable Locoregionally Advanced Esophageal Cancer: Initial Reporting of RTOG 0246

    SciTech Connect

    Swisher, Stephen G.; Winter, Kathryn A.; Komaki, Ritsuko U.; Ajani, Jaffer A.; Wu, Tsung T.; Hofstetter, Wayne L.; Konski, Andre A.; Willett, Christopher G.

    2012-04-01

    Purpose: The strategy of definitive chemoradiation with selective surgical salvage in locoregionally advanced esophageal cancer was evaluated in a Phase II trial in Radiation Therapy Oncology Group (RTOG)-affiliated sites. Methods and Materials: The study was designed to detect an improvement in 1-year survival from 60% to 77.5% ({alpha} = 0.05; power = 80%). Definitive chemoradiation involved induction chemotherapy with 5-fluorouracil (5-FU) (650 mg/mg{sup 2}/day), cisplatin (15 mg/mg{sup 2}/day), and paclitaxel (200 mg/mg{sup 2}/day) for two cycles, followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fraction) and daily 5-FU (300 mg/mg{sup 2}/day) with cisplatin (15 mg/mg{sup 2}/day) over the first 5 days. Salvage surgical resection was considered for patients with residual or recurrent esophageal cancer who did not have systemic disease. Results: Forty-three patients with nonmetastatic resectable esophageal cancer were entered from Sept 2003 to March 2006. Forty-one patients were eligible for analysis. Clinical stage was {>=}T3 in 31 patients (76%) and N1 in 29 patients (71%), with adenocarcinoma histology in 30 patients (73%). Thirty-seven patients (90%) completed induction chemotherapy followed by concurrent chemoradiation. Twenty-eight patients (68%) experienced Grade 3+ nonhematologic toxicity. Four treatment-related deaths were noted. Twenty-one patients underwent surgery following definitive chemoradiation because of residual (17 patients) or recurrent (3 patients) esophageal cancer,and 1 patient because of choice. Median follow-up of live patients was 22 months, with an estimated 1-year survival of 71%. Conclusions: In this Phase II trial (RTOG 0246) evaluating selective surgical salvage after definitive chemoradiation in locoregionally advanced esophageal cancer, the hypothesized 1-year RTOG survival rate (77.5%) was not achieved (1 year, 71%; 95% confidence interval< 54%-82%).

  17. Surgical treatment analysis of idiopathic esophageal achalasia

    PubMed Central

    de AQUINO, José Luis Braga; SAID, Marcelo Manzano; PEREIRA, Douglas Rizzanti; do AMARAL, Paula Casals; LIMA, Juliana Carolina Alves; LEANDRO-MERHI, Vânia Aparecida

    2015-01-01

    Background Idiopathic esophageal achalasia is an inflammatory disease of unknown origin, characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter in response to swallowing, with consequent dysphagia. Aim To demonstrate the results of surgical therapy in these patients, evaluating the occurred local and systemic complications. Methods Were studied retrospectively 32 patients, 22 of whom presented non-advanced stage of the disease (Stage I/II) and 10 with advanced disease (Stage III/IV). All of them had the clinical conditions to be submitted to surgery. The diagnoses were done by clinical, endoscopic, cardiological, radiological and esophageal manometry analysis. Pre-surgical evaluation was done with a questionnaire based on the most predisposing factors in the development of the disease and the surgical indication was based on the stage of the disease. Results The patients with non-advanced stages were submitted to cardiomyotomy with fundoplication, wherein in the post-surgical early assessment, only one (4,4%) presented pulmonary infection, but had a good outcome. In patients with advanced disease, seven were submitted to esophageal mucosectomy preserving the muscular layer, wherein one patient (14,2%) presented dehiscence of gastric cervical esophagus anastomosis as well as pulmonary infection; all of these complications were resolved with proper specific treatment; the other three patients with advanced stage were submitted to transmediastinal esophagectomy; two of them presented hydropneumothorax with good evolution, and one of them also presented fistula of the cervical esophagogastric anastomosis, but with spontaneous healing after conservative treatment and nutritional support. The two patients with fistula of the cervical anastomosis progressed to stenosis, with good results after endoscopic dilations. In the medium and long term assessment done in 23 patients, all of them reported improvement in life quality, with return to swallowing. Conclusion The strategy proposed for the surgical treatment of idiopathic esophageal achalasia according to the stages of the disease was of great value, due to post-surgical low morbidity complications and proper recovery of swallowing. PMID:26176243

  18. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis

    PubMed Central

    Sherrill, J D; KC, K; Wu, D; Djukic, Z; Caldwell, J M; Stucke, E M; Kemme, K A; Costello, M S; Mingler, M K; Blanchard, C; Collins, M H; Abonia, J P; Putnam, P E; Dellon, E S; Orlando, R C; Hogan, S P; Rothenb, M E

    2014-01-01

    The desmosomal cadherin desmoglein-1 (DSG1) is an essential intercellular adhesion molecule that is altered in various human cutaneous disorders; however, its regulation and function in allergic disease remains unexplored. Herein, we demonstrate a specific reduction in DSG1 in esophageal biopsies from patients with eosinophilic esophagitis (EoE), an emerging allergic disorder characterized by chronic inflammation within the esophageal mucosa. Further, we show that DSG1 gene silencing weakens esophageal epithelial integrity, and induces cell separation and impaired barrier function (IBF) despite high levels of desmoglein-3 (DSG3). Moreover, DSG1 deficiency induces transcriptional changes that partially overlap with the transcriptome of inflamed esophageal mucosa; notably, periostin, a multipotent pro-inflammatory extracellular matrix molecule, is the top induced overlapping gene. We further demonstrate that IBF is a pathological feature in EoE, which can be partially induced through the downregulation of DSG1 by interleukin-13 (IL-13). Taken together, these data identify a functional role for DSG1 and its dysregulation by IL-13 in the pathophysiology of EoE and suggest that the loss of DSG1 may potentiate allergic inflammation through the induction of pro-inflammatory mediators such as periostin. PMID:24220297

  19. Intramural esophagic hematoma secondary to coumarinic anticoagulation: a case report

    PubMed Central

    2009-01-01

    Esophagic Intramural Hematoma is an uncommon clinical condition, with a prognosis which is essentially benign. On most cases, a predisposing or precipitating factor may be seen, with the most common ones being the history of esophagic instrumentation, food impactations and thrombocytopenia. In the following manuscript, the authors present the case of a 54-years-old male with history of valve replacement surgery, who was treated at the Clinica Cardiovascular (Medellin, Colombia), with a clinical case of Intramural Esophagic Hematoma that was later confirmed to be due to a Coumarinic overanticoagulation. On this case, it is evidenced that Intramural Esophagic Hematoma is an unrecognized complication of Courmarinic anticoagulation therapy. PMID:20069068

  20. Eosinophilic esophagitis as paraneoplastic syndrome in a patient with ganglioneuroblastoma.

    PubMed

    Prader, S; Spalinger, J; Caduff, J; Hürlimann, S; Rischewski, J

    2015-05-01

    A 16-month-old boy presented with failure to thrive despite sufficient caloric intake, hypersalivation, abdominal pain, chronic diarrhea and blepharitis. An eosinophilic esophagitis (EoE) was diagnosed by esophageal biopsy. Dietary restrictions and topical steroid treatment lead to no improvement. Further diagnostic work-up revealed an intrathoracal, paraspinal ganglioneuroblastoma. After operative extirpation of the tumour, all initial symptoms resolved. An esophageal control biopsy 4 weeks after tumour resection was normal. This is the first report of eosinophilic esophagitis as part of a paraneoplastic syndrome in a patient with a malignant disease other than a carcinoma. PMID:25985452

  1. Esophageal cancer: Recent advances in screening, targeted therapy, and management

    PubMed Central

    Gaur, Puja; Kim, Min P.; Dunkin, Brian J.

    2014-01-01

    The incidence of esophageal cancer remains on the rise worldwide and despite aggressive research in the field of gastrointestinal oncology, the survival remains poor. Much remains to be defined in esophageal cancer, including the development of an effective screening tool, identifying a good tumor marker for surveillance purposes, ways to target esophageal cancer stem cells as well as circulating tumor cells, and developing minimally invasive protocols to treat early-stage disease. The goal of this chapter is to highlight some of the recent advances and ongoing research in the field of esophageal cancer. PMID:25395880

  2. Aortic Pseudoaneurysm Secondary to Mediastinitis due to Esophageal Perforation

    PubMed Central

    Zuluaga, Claudia Patricia; Aluja Jaramillo, Felipe; Velásquez Castaño, Sergio Andrés; Rivera Bernal, Aura Lucía; Granada, Julio Cesar; Carrillo Bayona, Jorge Alberto

    2016-01-01

    Esophageal perforation is a condition associated with high morbidity and mortality rates; it requires early diagnosis and treatment. The most common complication of esophageal rupture is mediastinitis. There are several case reports in the literature of mediastinitis secondary to esophageal perforation and development of aortic pseudoaneurysm as a complication. We report the case of a patient with an 8-day history of esophageal perforation due to foreign body (fishbone) with mediastinitis and aortic pseudoaneurysm. The diagnosis was made using Computed Tomography (CT) with intravenous and oral water-soluble contrast material. An esophagogastroduodenoscopy did not detect the perforation. PMID:26977330

  3. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed...

  4. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed...

  5. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed...

  6. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed...

  7. 47 CFR 90.761 - EA and Regional licenses.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Regional licenses. (a) EA licenses for spectrum blocks listed in Table 2 of § 90.721(b) are available in 175 Economic Areas (EAs) as defined in § 90.7. (b) Regional licenses for spectrum blocks listed...

  8. Parenteral nutrition in esophageal cancer patients.

    PubMed Central

    Daly, J M; Massar, E; Giacco, G; Frazier, O H; Mountain, C F; Dudrick, S J; Copeland, E M

    1982-01-01

    A review of operative therapy in 244 patients with esophageal cancer from 1960 to 1980 was done to evaluate the impact of TPN in 72 patients treated from 1973 to 1980 with 43 non-TPN patients treated during the same period and to 129 patients operated upon before 1973. Mean age, sex distribution, site, stage, and treatment of the disease were similar for the two study groups. The TPN group lost less weight during treatment (3 lbs vs. 11 lbs) and had fewer overall complications postoperatively (24% vs. 41%). Significant reductions in major wound, infectious, and postoperative complications were noted in these patients who received at least 5 days of preoperative TPN compared with postoperative TPN or the non-TPN groups (4% vs. 24% and 23%). Malnourished esophageal cancer patients can more safely undergo aggressive operative therapy and radiation treatment when adequate perioperative nutritional support is added to the treatment armamentarium. PMID:6807225

  9. GWAS identifies four novel eosinophilic esophagitis loci

    PubMed Central

    Sleiman, Patrick MA; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J.; Furuta, Glenn T.; Spergel, Jonathan M.; Hakonarson, Hakon

    2014-01-01

    Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the esophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune disease, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the esophagus. The identification of five EoE loci, not only expands our etiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, esophageal inflammation and remodeling. PMID:25407941

  10. EAS array of the NEVOD Experimental Complex

    NASA Astrophysics Data System (ADS)

    Yashin, I. I.; Amelchakov, M. B.; Ampilogov, N. V.; Barbashina, N. S.; Bogdanov, A. G.; Chiavassa, A.; Fomenko, S. V.; Kamlev, N. N.; Khokhlov, S. S.; Kindin, V. V.; Kokoulin, R. P.; Kompaniets, K. G.; Kutovoy, V. Yu; Likiy, O. I.; Mannocchi, G.; Ovchinnikov, V. V.; Petrukhin, A. A.; Saavedra, O.; Trinchero, G.; Shestakov, V. V.; Shulzhenko, I. A.; Shutenko, V. V.

    2015-08-01

    A new setup for registration of the electromagnetic component of the EAS at the “knee” region of the energy spectrum of primary cosmic rays (PCR) is now under construction on the basis of the experimental complex NEVOD-DECOR (Moscow, Russia). The EAS array detecting system has a cluster organization. Clusters are located in the MEPhI campus. The specific features of the array registering system that provides particle detection, data acquisition, cluster synchronization and events selection are discussed. The results of counter characteristics study are also presented.

  11. Reversal of lower esophageal sphincter hypotension and esophageal aperistalsis after treatment for hypothyroidism

    SciTech Connect

    Eastwood, G.L.; Braverman, L.E.; White, E.M.; Vander Salm, T.J.

    1982-08-01

    A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with /sup 131/I and documented a fall in LES pressure. We propose that abnormal smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism.

  12. Reversal of lower esophageal sphincter hypotension and esophageal aperistalsis after treatment for hypothyroidism.

    PubMed

    Eastwood, G L; Braverman, L E; White, E M; Vander Salm, T J

    1982-08-01

    A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with 131I and documented a fall in LES pressure. We propose that abnormal smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism. PMID:7119407

  13. Significance of feeding dysfunction in eosinophilic esophagitis.

    PubMed

    Menard-Katcher, Calies; Henry, Michelle; Furuta, Glenn T; Atkins, Dan; Maune, Nancy Creskoff; Haas, Angela M

    2014-08-21

    Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis (EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth. PMID:25152606

  14. Eosinophilic Esophagitis: update on treatment approaches

    PubMed Central

    Fotis, L; Xatzipsalti, M; Papadopoulou, A

    2012-01-01

    ?osinophilic esophagitis (EoE) is a clinical entity with continuously increasing incidence in children and adults. Diet therapy and corticosteroids are the most important therapeutic interventions currently used, while new therapies are being developed, based on the research of the disease mechanisms. In this review we assess the results of the latest clinical trials on management of patients with EoE, and the advances in the development of novel drug therapies. Hippokratia 2012; 16 (3): 200-204 PMID:23935283

  15. Significance of feeding dysfunction in eosinophilic esophagitis

    PubMed Central

    Menard-Katcher, Calies; Henry, Michelle; Furuta, Glenn T; Atkins, Dan; Maune, Nancy Creskoff; Haas, Angela M

    2014-01-01

    Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis (EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth. PMID:25152606

  16. Advances in Clinical Management of Eosinophilic Esophagitis

    PubMed Central

    Dellon, Evan S.; Liacouras, Chris A.

    2014-01-01

    EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines—EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885

  17. High Goblet Cell Count Is Inversely Associated with Ploidy Abnormalities and Risk of Adenocarcinoma in Barrett’s Esophagus

    PubMed Central

    Sanchez, Carissa A.; Liu, Karen; Fong, Pui Yee; Li, Xiaohong; Cowan, David S.; Rabinovitch, Peter S.; Reid, Brian J.; Blount, Patricia L.

    2015-01-01

    Purpose Goblet cells may represent a potentially successful adaptive response to acid and bile by producing a thick mucous barrier that protects against cancer development in Barrett's esophagus (BE). The aim of this study was to determine the relationship between goblet cells (GC) and risk of progression to adenocarcinoma, and DNA content flow cytometric abnormalities, in BE patients. Experimental Design Baseline mucosal biopsies (N=2988) from 213 patients, 32 of whom developed cancer during the follow up period, enrolled in a prospective dynamic cohort of BE patients were scored in a blinded fashion, for the total number (#) of GC, mean # of GC/crypt (GC density), # of crypts with ≥ 1 GC, and the proportion of crypts with ≥1 GC, in both dysplastic and non-dysplastic epithelium separately. The relationship between these four GC parameters and DNA content flow cytometric abnormalities and adenocarcinoma outcome was compared, after adjustment for age, gender, and BE segment length. Results High GC parameters were inversely associated with DNA content flow cytometric abnormalities, such as aneuploidy, ploidy >2.7N, and an elevated 4N fraction > 6%, and with risk of adenocarcinoma. However, a Kaplan-Meier analysis showed that the total # of GC and the total # crypts with ≥1 GC were the only significant GC parameters (p<0.001 and 0.003, respectively). Conclusions The results of this study show, for the first time, an inverse relationship between high GC counts and flow cytometric abnormalities and risk of adenocarcinoma in BE. Further studies are needed to determine if GC depleted foci within esophageal columnar mucosa are more prone to neoplastic progression or whether loss of GC occurs secondary to underlying genetic abnormalities. PMID:26230607

  18. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... which may consist of Broadband Radio Service (BRS), or Educational Broadband Service (EBS) stations; DBS... for the duration of the EAS message. SDARS and DBS EAS equipment requirement SDARS DBS EAS decoder 1 Y... All SDARS and DBS providers may comply with this requirement by providing a means to switch...

  19. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... which may consist of Broadband Radio Service (BRS), or Educational Broadband Service (EBS) stations; DBS... for the duration of the EAS message. SDARS and DBS EAS equipment requirement SDARS DBS EAS decoder 1 Y... All SDARS and DBS providers may comply with this requirement by providing a means to switch...

  20. 47 CFR 11.11 - The Emergency Alert System (EAS).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... which may consist of Broadband Radio Service (BRS), or Educational Broadband Service (EBS) stations; DBS... for the duration of the EAS message. SDARS and DBS EAS equipment requirement SDARS DBS EAS decoder 1 Y... All SDARS and DBS providers may comply with this requirement by providing a means to switch...

  1. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Environmental Assessments (EA). 230.10 Section 230.10 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROCEDURES FOR IMPLEMENTING NEPA § 230.10 Environmental Assessments (EA). (a) Purpose. An EA is a brief document which...

  2. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... determining whether to prepare an EIS or a FONSI (40 CFR 1508.9). The district commander is responsible for... engineering reports not requiring an EIS, the EA may be combined with or integrated into the report. The same guidance on combining or integrating an EIS within the report shall apply equally to an EA. Where the EA...

  3. 33 CFR 230.10 - Environmental Assessments (EA).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... determining whether to prepare an EIS or a FONSI (40 CFR 1508.9). The district commander is responsible for... engineering reports not requiring an EIS, the EA may be combined with or integrated into the report. The same guidance on combining or integrating an EIS within the report shall apply equally to an EA. Where the EA...

  4. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... specified in 40 CFR 1506.6. (d) Mitigated FONSI. If an EA is completed and the NEPA Compliance Coordinator... Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11 Preparation of an EA. (a) When to prepare. The Trust will begin the preparation of an EA (or require it to...

  5. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... specified in 40 CFR 1506.6. (d) Mitigated FONSI. If an EA is completed and the NEPA Compliance Coordinator... Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11 Preparation of an EA. (a) When to prepare. The Trust will begin the preparation of an EA (or require it to...

  6. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specified in 40 CFR 1506.6. (d) Mitigated FONSI. If an EA is completed and the NEPA Compliance Coordinator... Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11 Preparation of an EA. (a) When to prepare. The Trust will begin the preparation of an EA (or require it to...

  7. 36 CFR 1010.11 - Preparation of an EA.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... specified in 40 CFR 1506.6. (d) Mitigated FONSI. If an EA is completed and the NEPA Compliance Coordinator... Section 1010.11 Parks, Forests, and Public Property PRESIDIO TRUST ENVIRONMENTAL QUALITY § 1010.11 Preparation of an EA. (a) When to prepare. The Trust will begin the preparation of an EA (or require it to...

  8. 14 CFR 1216.308 - Supplemental EAs and EISs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... previous EAs or EISs (see 40 CFR 1502.9). If changed circumstances require preparation of a supplemental EA or EIS, such document will be prepared following the same general process as the original EA or EIS. No new scoping is required for a supplemental EIS; however, NASA may choose to conduct scoping....

  9. 14 CFR 1216.308 - Supplemental EAs and EISs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... previous EAs or EISs (see 40 CFR 1502.9). If changed circumstances require preparation of a supplemental EA or EIS, such document will be prepared following the same general process as the original EA or EIS. No new scoping is required for a supplemental EIS; however, NASA may choose to conduct scoping....

  10. Lidocaine inhibition of esophageal peristalsis and lower esophageal sphincter pressure in baboons.

    PubMed

    Sinar, D R; Carey, L C; Cordova, C; Fletcher, J R; Castell, D O

    1985-11-01

    Intravenous lidocaine was infused at 0.82 ml/min in a concentration of 1.2 mg/ml (2.3 mg/kg) for 120 min in awake chair-restrained baboons (Papio anubis), and measurements of esophageal peristalsis and LES pressure were compared before and after lidocaine or control infusions. Lidocaine produced a progressive and significant (P less than 0.05) decrease in amplitude in the peristaltic wave in the smooth muscle portion of the distal esophagus during the 120-min infusion. Lower esophageal sphincter pressure was similarly significantly lower than control after the infusion of lidocaine (P less than 0.05). Velocity and duration of the peristaltic wave were unchanged during the infusion. The decreased amplitude occurred during therapeutic and stable serum concentrations of lidocaine. It did not appear that the inhibitory effect of lidocaine was due to an induction of prostaglandin synthesis, because pretreatment of animals with indomethacin did not change the inhibitory effect of lidocaine, and serum metabolites of prostacyclin decreased during the infusion. Furthermore, the inhibitory effect of lidocaine was not topical. The response to the muscarinic agonist, bethanechol was similar in lidocaine-treated animals and control animals. The preservation of a bethanechol response after lidocaine inhibition of LES pressure and distal esophageal amplitude suggests that lidocaine acts proximal to the muscarinic receptor in the esophageal body and smooth muscle portion of the lower esophageal sphincter. This study suggests that lidocaine produces an inhibitory effect on the peristaltic wave and lower esophageal sphincter pressure that is similar to inhibitory effects described after anticholinergic agents and calcium channel blocking drugs, but intravenous lidocaine infusion requires a longer period of time to produce inhibition of muscle function. PMID:2865090

  11. Eosinophilic esophagitis: From pathophysiology to treatment

    PubMed Central

    D’Alessandro, Alessandra; Esposito, Dario; Pesce, Marcella; Cuomo, Rosario; De Palma, Giovanni Domenico; Sarnelli, Giovanni

    2015-01-01

    Eosinophilic esophagitis (EoE) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and reflux-like symptoms. Traditionally considered a pediatric disease, the number of adult patients with EoE is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of EoE, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of EoE in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the first-line therapy in children, but this approach appears less effective in adults patients, who often require steroids; despite medical treatments, EoE is complicated in some cases by esophageal stricture and stenosis, that require additional endoscopic treatments. This review summarizes the evidence on EoE pathophysiology and illustrates the safety and efficacy of the most recent medical and endoscopic treatments. PMID:26600973

  12. A Review of Esophageal Chest Pain

    PubMed Central

    Coss-Adame, Enrique

    2015-01-01

    Noncardiac chest pain is a term that encompasses all causes of chest pain after a cardiac source has been excluded. This article focuses on esophageal sources for chest pain. Esophageal chest pain (ECP) is common, affects quality of life, and carries a substantial health care burden. The lack of a systematic approach toward the diagnosis and treatment of ECP has led to significant disability and increased health care costs for this condition. Identifying the underlying cause(s) or mechanism(s) for chest pain is key for its successful management. Common etiologies include gastroesophageal reflux disease, esophageal hypersensitivity, dysmotility, and psychological conditions, including panic disorder and anxiety. However, the pathophysiology of this condition is not yet fully understood. Randomized controlled trials have shown that proton pump inhibitor therapy (either omeprazole, lansoprazole, or rabeprazole) can be effective. Evidence for the use of antidepressants and the adenosine receptor antagonist theophylline is fair. Psychological treatments, notably cognitive behavioral therapy, may be useful in select patients. Surgery is not recommended. There remains a large unmet need for identifying the phenotype and prevalence of pathophysiologic mechanisms of ECP as well as for well-designed multicenter clinical trials of current and novel therapies. PMID:27134590

  13. Esophageal Perforation: A Rare Complication of Transesophageal Echocardiography in a Patient with Asymptomatic Esophagitis

    PubMed Central

    Ahmed, Kabir; Lal, Yasir; Condron, Steven

    2012-01-01

    Transesophageal echocardiography (TEE) is a commonly used procedure in patients with suspected endocarditis. A rare but dreadful complication of this procedure is perforation of the esophagus. We report the case of an elderly female with multiple comorbidities, who presented with polyarticular septic arthritis. TEE was performed to rule out endocarditis. Though the standard procedure protocol was followed, she developed esophageal perforation. It was managed with esophageal stenting but she developed multiorgan failure and did not survive. This case highlights the potential of severe morbidity and mortality associated with TEE. Appropriate screening must be done and high-risk individuals must be identified before such procedures are attempted. PMID:23341798

  14. Polymorphisms in alcohol-metabolizing enzymes and esophageal carcinoma susceptibility: a Dutch Caucasian case-control study.

    PubMed

    Dura, Polat; Berkers, Tineke; van Veen, Elke M; Salomon, Jody; te Morsche, Rene H M; Roelofs, Hennie M J; Kristinsson, Jon O; Wobbes, Theo; Witteman, Ben J M; Tan, Adriaan C I T L; Drenth, Joost P H; Peters, Wilbert H M

    2013-11-01

    Esophageal cancer (EC), mainly consisting of squamous cell carcinoma (ESCC) in the Eastern world and adenocarcinoma (EAC) in the Western world, is strongly associated with dietary factors such as alcohol use. We aimed to clarify the modifying role in EC etiology in Caucasians of functional genotypes in alcohol-metabolizing enzymes. In all, 351 Caucasian patients with EC and 430 matched controls were included and polymorphisms in CYP2E1, ADH and near ALDH2 genes were determined. In contrast to the results on ESCC in mainly Asian studies, we found that functional genotypes of alcohol-metabolizing enzymes were not significantly associated with EAC or ESCC in an European population. PMID:24048263

  15. Resection of a Submucosal Tumor-Like Superficial Carcinoma in Middle Thoracic Esophagus Concomitant with Mucosal Adenocarcinoma and Submucosal Squamous Cell Carcinoma: A Case Report and Review of Literature.

    PubMed

    Yamamoto, Soichiro; Kumaki, Nobue; Makuuchi, Hiroyasu; Ozawa, Soji; Shimada, Hideo; Chino, Osamu; Kazuno, Akihito; Yasuda, Seiei; Tamayama, Takaaki; Sakai, Izumi

    2015-09-01

    A 67-year-old man was pointed out mucosal irregularity on health check-up and was referred to our institution. Diagnostic examinations were performed and an aggregated type 0-IIa lesion having 3 small protrusions was recognized in the middle thoracic esophagus. Endoscopic biopsy led to diagnosis of esophageal cancer concomitant with adenocarcinoma and squamous cell carcinoma. Thoracic esophagectomy with 3-fields lymph node dissection was performed via a right thoracoabdominal approach and reconstructed with stomach roll. Three submucosal tumors like small protrusions were recognized in resected specimen. One of them was well differentiated tubular adenocarcinoma which occupied in mucosal layer. The other two were moderately differentiated squamous cell carcinoma. They existed very near but no connection was recognized by serial section. The adenocarcinoma existing in middle esophagus is very rare. Almost all of them were submucosal or advanced cancers. When we searched with the ICHUSHI database (a domestic medical literature database service provided by the NPO Japan Medical Abstracts Society) and the PubMed database, there was no report of mucosal adenocarcinoma occurred in middle thoracic esophagus in the past 10 years. Then this report was thought to be the first report of mucosal adenocarcinoma in middle thoracic esophagus in the world. PMID:26369262

  16. 47 CFR 11.31 - EAS protocol.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... End Of Message (EOM) Codes. (1) The Preamble and EAS Codes must use Audio Frequency Shift Keying at a... and End of Message code. ZCZC—This is the identifier, sent as ASCII characters ZCZC to indicate the start of ASCII code. ORG—This is the Originator code and indicates who originally initiated...

  17. 24 CFR 50.31 - The EA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 1 2013-04-01 2013-04-01 false The EA. 50.31 Section 50.31 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.31 The...

  18. 24 CFR 50.31 - The EA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false The EA. 50.31 Section 50.31 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.31 The...

  19. 24 CFR 50.31 - The EA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false The EA. 50.31 Section 50.31 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.31 The...

  20. 24 CFR 50.31 - The EA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false The EA. 50.31 Section 50.31 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.31 The...

  1. 24 CFR 50.31 - The EA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 1 2014-04-01 2014-04-01 false The EA. 50.31 Section 50.31 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development PROTECTION AND ENHANCEMENT OF ENVIRONMENTAL QUALITY Environmental Assessments and Related Reviews § 50.31 The...

  2. TRANSPORT PROPERTY MEASUREMENTS OF HFC-236EA

    EPA Science Inventory

    The report gives results of an evaluation of transport properties of 1,1,1,2,3,3,-hexafluoropropane (HFC-236ea), with liquid viscosity and thermal conductivity being the two main transport properties of interest. In addition, the specific heat and density of refrigerant/lubrican...

  3. TRANSPORT PROPERTY MEASUREMENTS OF HFC-236EA

    EPA Science Inventory

    The report gives results of an evaluation of transport properties of 1, 1, 1, 2, 3, 3-hexafluoropropane (HFC-236ea), with liquid viscosity and thermal conductivity being the two main transport properties of interest. In addition, the specific heat and density of refrigerant/lubri...

  4. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... emergency messages from sources such as the National Weather Service or local emergency management offices... Center (EOC) or State Capital. Messages are sent via the State Relay Network. (d) State Relay (SR) is a source of EAS State messages. It is part of the State Relay Network and relays National and State...

  5. Adenocarcinoma - chest x-ray (image)

    MedlinePlus

    This chest x-ray shows adenocarcinoma of the lung. There is a rounded light spot in the right upper lung (left side ... density. Diseases that may cause this type of x-ray result would be tuberculous or fungal granuloma, and ...

  6. Gene expression profiling analysis of lung adenocarcinoma.

    PubMed

    Xu, H; Ma, J; Wu, J; Chen, L; Sun, F; Qu, C; Zheng, D; Xu, S

    2016-03-01

    The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma. PMID:26840709

  7. Primary adenocarcinoma of the seminal vesicle.

    PubMed

    Tarján, M; Ottlecz, I; Tot, T

    2009-01-01

    Primary adenocarcinomas of the seminal vesicle (SVC) are very rare and poorly understood neoplasms with only somewhat more than 50 histologically confirmed cases reported in the literature. We demonstrate a case of SVC and discuss the problems related to diagnosis in this tumor. PMID:19468449

  8. Primary adenocarcinoma of the seminal vesicle

    PubMed Central

    Tarján, M.; Ottlecz, I.; Tot, T.

    2009-01-01

    Primary adenocarcinomas of the seminal vesicle (SVC) are very rare and poorly understood neoplasms with only somewhat more than 50 histologically confirmed cases reported in the literature. We demonstrate a case of SVC and discuss the problems related to diagnosis in this tumor. PMID:19468449

  9. Chromogranin A expression in human colonic adenocarcinoma.

    PubMed

    Romeo, R; Pellitteri, R; Mazzone, V; Marcello, M F

    2002-01-01

    The presence of CgA positive cells occuring in scattered elements or in clusters within human colonic adenocarcinomas has been documented in recent data. The number of these cases has ranged from 10% to 40% depending on the method of demonstration. The aim of this study is to assess the presence of CgA positive cells on a set of 60 tumours that, by standard histological procedures, were classified as well differentiated (n.5), moderately differentiated (n.48) and poorly differentiated (n.7) adenocarcinoma. 4-5 microm thick sections were processed by means of immunoperoxidase method using the primary CgA monoclonal antibody. Our results showed CgA positive cells in two cases of poorly differentiated and three cases of moderately differentiated adenocarcinoma. These specimens (8% of cases) showed diffuse, irregular areas of CgA immunoreactive cells as components of the neoplasm. These cases could be considerer as "mixed exocrine and neuroendocrine carcinoma" that develops from the same stem cell which differentiates into two atypical cell lines. Therefore, we suggest that to carry out a proper adenocarcinoma histological examination, and to establish a consequent therapy, not only common staining techniques but also immunohistochemical methods should be used. PMID:12437144

  10. Gene expression profiling analysis of lung adenocarcinoma

    PubMed Central

    Xu, H.; Ma, J.; Wu, J.; Chen, L.; Sun, F.; Qu, C.; Zheng, D.; Xu, S.

    2016-01-01

    The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma. PMID:26840709

  11. Periampullary adenocarcinoma: analysis of 5-year survivors.

    PubMed Central

    Yeo, C J; Sohn, T A; Cameron, J L; Hruban, R H; Lillemoe, K D; Pitt, H A

    1998-01-01

    OBJECTIVE: This single-institution experience retrospectively reviews the outcomes in a group of patients treated 5 or more years ago by pancreaticoduodenectomy for periampullary adenocarcinoma. SUMMARY BACKGROUND DATA: Controversy exists regarding the benefit of resection for periampullary adenocarcinoma, particularly for pancreatic tumors. Many series report only Kaplan-Meier actuarial 5-year survival rates. There are believed to be discrepancies between the actuarial 5-year survival data and the actual 5-year survival rates. METHODS: From April 1970 through May 1992, 242 patients underwent pancreaticoduodenal resection for periampullary adenocarcinoma at The Johns Hopkins Hospital. Follow-up was complete through May 1997. All pathology specimens were reviewed and categorized. Actual 5-year survival rates were calculated. The demographic, intraoperative, pathologic, and postoperative features of patients surviving > or =5 years were compared with those of patients who survived <5 years. RESULTS: Of the 242 patients with resected periampullary adenocarcinoma, 149 (62%) were pancreatic primaries, 46 (19%) arose in the ampulla, 30 (12%) were distal bile duct cancers, and 17 (7%) were duodenal cancers. There was a 5.3% operative mortality rate during the 22 years of the review, with a 2% operative mortality rate in the last 100 patients. There were 58 5-year survivors, 28 7-year survivors, and 7 10-year survivors. The tumor-specific 5-year actual survival rates were pancreatic 15%, ampullary 39%, distal bile duct 27%, and duodenal 59%. When compared with patients who did not survive 5 years, the 5-year survivors had a significantly higher percentage of well-differentiated tumors (14% vs. 4%; p = 0.02) and higher incidences of negative resection margins (98% vs. 73%, p < 0.0001) and negative nodal status (62% vs. 31%, p < 0.0001). The tumor-specific 10-year actuarial survival rates were pancreatic 5%, ampullary 25%, distal bile duct 21%, and duodenal 59%. CONCLUSIONS: Among patients with periampullary adenocarcinoma treated by pancreaticoduodenectomy, those with duodenal adenocarcinoma are most likely to survive long term. Five-year survival is less likely for patients with ampullary, distal bile duct, and pancreatic primaries, in declining order. Resection margin status, resected lymph node status, and degree of tumor differentiation also significantly influence long-term outcome. Particularly for patients with pancreatic adenocarcinoma, 5-year survival is not equated with cure, because many patients die of recurrent disease >5 years after resection. Images Figure 1. PMID:9637545

  12. FGFR1 Amplification Is Often Homogeneous and Strongly Linked to the Squamous Cell Carcinoma Subtype in Esophageal Carcinoma

    PubMed Central

    Burkhardt, Lia; Simon, Ronald; Steurer, Stefan; Burdak-Rothkamm, Susanne; Jacobsen, Frank; Sauter, Guido; Krech, Till

    2015-01-01

    Background and Aims Amplification of the fibroblast growth factor receptor 1 (FGFR1) is believed to predict response to multi-kinase inhibitors targeting FGFR1. Esophageal cancer is an aggressive disease, for which novel targeted therapies are highly warranted. Methods This study was designed to investigate the prevalence and clinical significance of FGFR1 amplification in a tissue microarray containing 346 adenocarcinomas and 254 squamous cell carcinomas of the esophagus, using dual-labeling fluorescence in situ hybridization (FISH) analysis. Results FGFR1 amplification, defined as a ratio of FGFR1:centromere 8 copy numbers ≥ 2.0, was more frequently seen in squamous cell carcinoma (8.9% of 202 interpretable cases) than in adenocarcinoma (1.6% of 308; p<0.0001). There was no association between FGFR1 amplification and tumor phenotype or clinical outcome. To study potential heterogeneity of FGFR1 amplification, all available tumor blocks from 23 FGFR1 amplified tumors were analyzed on conventional large sections. This analysis revealed complete homogeneity of FGFR1 amplification in 20 (86.9%) primary tumors and in all available lymph node metastases. Remarkably, FGFR1 amplification was also seen in dysplasia adjacent to tumor in 6 of 9 patients with FGFR1 amplified primary cancers. Conclusions In conclusion, FGFR1 amplification occurs in a relevant subgroup of carcinomas of the esophagus and may play a particular role for development of squamous cell cancers. The high homogeneity of FGFR1 amplification suggests that patients with FGFR1 amplified esophageal cancers may particularly benefit from anti-FGFR1 therapies and prompt for clinical studies in this tumor type. PMID:26555375

  13. Prevention of esophageal strictures after endoscopic submucosal dissection

    PubMed Central

    Kobayashi, Shinichiro; Kanai, Nobuo; Ohki, Takeshi; Takagi, Ryo; Yamaguchi, Naoyuki; Isomoto, Hajime; Kasai, Yoshiyuki; Hosoi, Takahiro; Nakao, Kazuhiko; Eguchi, Susumu; Yamamoto, Masakazu; Yamato, Masayuki; Okano, Teruo

    2014-01-01

    Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have recently been accepted as less invasive methods for treating patients with early esophageal cancers such as squamous cell carcinoma and dysplasia of Barrett’s esophagus. However, the large defects in the esophageal mucosa often cause severe esophageal strictures, which dramatically reduce the patient’s quality of life. Although preventive endoscopic balloon dilatation can reduce dysphagia and the frequency of dilatation, other approaches are necessary to prevent esophageal strictures after ESD. This review describes several strategies for preventing esophageal strictures after ESD, with a particular focus on anti-inflammatory and tissue engineering approaches. The local injection of triamcinolone acetonide and other systemic steroid therapies are frequently used to prevent esophageal strictures after ESD. Tissue engineering approaches for preventing esophageal strictures have recently been applied in basic research studies. Scaffolds with temporary stents have been applied in five cases, and this technique has been shown to be safe and is anticipated to prevent esophageal strictures. Fabricated autologous oral mucosal epithelial cell sheets to cover the defective mucosa similarly to how commercially available skin products fabricated from epidermal cells are used for skin defects or in cases of intractable ulcers. Fabricated autologous oral-mucosal-epithelial cell sheets have already been shown to be safe. PMID:25386058

  14. Effects of effortful swallow on esophageal function in healthy adults

    PubMed Central

    NEKL, C. G.; LINTZENICH, C. R.; LENG, X.; LEVER, T.; BUTLER, S. G.

    2016-01-01

    Background Treatment for esophageal dysmotility is currently limited to primarily pharmacologic intervention, which has questionable utility and frequently associated negative side effects. A potential behavioral intervention for esophageal dysmotility is the effortful oropharyngeal swallow. A previous pilot study using water perfusion manometry found an increase in distal esophageal amplitudes during effortful vs non-effortful swallowing. The current study sought to duplicate the previous study with improvements in methodology. Methods The effects of swallow condition (effortful vs non-effortful), sensor site, and gender on esophageal amplitude, duration, velocity, and bolus clearance were examined for 18 adults (nine males and nine females, mean age = 29.9 years) via combined solid-state manometry and intraluminal impedance. Key Results The effortful swallow condition yielded significantly higher esophageal amplitudes across all sensor locations (P < 0.05). Further, the effortful swallowing decreased the risk of incomplete bolus clearance when compared with non-effortful swallowing (OR: 0.51; 95% CI: 0.30–0.86). Conclusions & Inferences With improved manometric instrumentation, larger participant numbers, and methodology that controlled for potential confounding factors, this study confirms and advances the results of the previous pilot study: Volitional manipulation of the oropharyngeal phase of swallowing using the effortful swallow indeed affects esophageal physiology. Thus, the effortful swallow offers a behavioral manipulation of the esophageal phase of swallowing, and future studies will determine its clinical potential for treating esophageal dysmotility in patient populations. PMID:22316290

  15. The functional relationships between hiatal hernia and reflux esophagitis.

    PubMed

    Park, H J; Lee, J D; Jung, J K; Moon, B S; Collins, P J; Park, I S

    1996-08-01

    The purpose of this research was to investigate functional studies by which the hiatal hernia (HH) may be relevant to a reflux esophagitis (RE). Group I consisted of healthy controls who were endoscopically normal (n = 21). Group II consisted of patients with hiatal hernia but no reflux esophagitis (n = 8). Group III had patients with hiatal hernia with reflux esophagitis (n = 9). Group IV had patients with reflux esophagitis but no hiatal hernia (n = 16). Esophageal manometry, ambulatory 24 hour intraesophageal pH monitoring, acid clearance test, and gastric emptying scan were performed in each of the patients. The contraction amplitude at 3 cm above the lower esophageal sphincter did not differ significantly among the four groups, but the mean lower esophageal sphincter pressure was significantly decreased in group II. The DeMeester score in ambulatory 24 hour intraesophageal pH monitoring was significantly higher in group III compared with the controls. No significant difference among the groups was found with respect to acid clearance. Total and proximal gastric emptying times (T1/2) were significantly delayed in group III. We found that hiatal hernia combined with delayed gastric emptying may bear a relationship to the multifactorial origins of reflux esophagitis, and we suggest a rationale for using prokinetic agents as the therapeutic regimen in patients with HH complicated by RE. PMID:8942298

  16. RET Rearrangements in Lung Adenocarcinoma and Radiation

    PubMed Central

    Dacic, Sanja; Luvison, Alyssa; Evdokimova, Viktoria; Kelly, Lindsey; Siegfried, Jill M.; Villaruz, Liza C.; Socinski, Mark A.; Nikiforov, Yuri E.

    2016-01-01

    Background RET rearrangement, a hallmark of radiation-induced thyroid cancer, has been reported to occur in 1% of lung adenocarcinoma patients. Patients with this rearrangement tend to be younger and never smokers, raising a possibility of other causes, such as radiation. We hypothesized that RET chromosomal rearrangement may represent a genetic mechanism of radiation-induced lung cancer. Methods Two hundred forty-five consecutive primary lung adenocarcinomas without history of radiation and 38 lung adenocarcinoma patients with a history of therapeutic radiation for breast carcinoma or mediastinal Hodkgin lymphoma were tested for RET rearrangement by fluorescence in situ hybridization. Human lung adenocarcinoma cells (201T) were subjected to γ radiation and tested for RET gene fusions by reverse transcriptase-polymerase chain reaction and Southern blot hybridization. Results We identified one case with RET rearrangement in the group without history of radiation (1 of 240; 0.4%) and two cases in the group with history of radiation (2 of 37; 5.4%; P=0.0436). Both these patients were women, who were former smokers with a history of breast carcinoma treated with surgery and radiation. Furthermore, we found that RET fusions could be directly induced in 201T human lung cells by exposure to 1 Gy of γ radiation. All fusions identified were between RET and KIF5B genes, and no RET fusions to CCDC6 or NCOA4 genes, characteristic for thyroid cancer, were identified in the irradiated lung cells. Conclusion RET fusions may represent a genetic mechanism of radiation-induced lung adenocarcinoma. PMID:24346100

  17. [Clinicopathological study of salivary gland adenocarcinomas].

    PubMed

    Iwasaki, K; Ono, I; Ebihara, S

    1989-12-01

    A total of 27 cases of salivary gland adenocarcinomas were studied from clinicopathological view point. Adenocarcinomas of the salivary gland were microscopically subclassified into 3 groups according to Luna's classification: Salivary duct carcinomas histologically resembled the ductal carcinoma of the breast, displayed nuclear atypia and had poorer prognosis than the other subclasses of salivary gland adenocarcinomas. Terminal duct carcinomas lacked in nuclear atypia and displayed a variety of growth patterns, including papillary, cribriform, tubular, and solid. Some terminal duct carcinomas showed prominent mucin-production. Epithelial-myoepithelial carcinomas had clear cytoplasms and exuberant glycogen. In addition to the clinicopathological study, nuclear areas of the tumor cells were measured in each of the 27 salivary gland adenocarcinomas, and mean nuclear area (MMA) and standard deviation (SD) were calculated. The group with more than 50 microns 2 of MNA had poorer prognosis than the group with 50 microns 2 or less of MNA, and the group with more than 13 microns 2 of SD had poorer prognosis than the group with 13 microns 2 or less of SD. Finally, immunohistochemical study was performed against various markers including keratin, epithelial membrane antigen, lactoferrin, S-100 protein, CEA, etc., using the Avidin-biotin-peroxidase complex method. Lactoferrin was present in most of the salivary duct carcinomas, on the other hand, S-100 protein was detected in all of the five cases of the terminal duct carcinoma investigated. But immunohistochemical study is not especially useful in distinguishing subclasses of salivary gland adenocarcinomas or investigating the origin of tumor cells. PMID:2559959

  18. LINE-1 expression and retrotransposition in Barrett's esophagus and esophageal carcinoma.

    PubMed

    Doucet-O'Hare, Tara T; Rodi?, Nemanja; Sharma, Reema; Darbari, Isha; Abril, Gabriela; Choi, Jungbin A; Young Ahn, Ji; Cheng, Yulan; Anders, Robert A; Burns, Kathleen H; Meltzer, Stephen J; Kazazian, Haig H

    2015-09-01

    Barrett's esophagus (BE) is a common disease in which the lining of the esophagus transitions from stratified squamous epithelium to metaplastic columnar epithelium that predisposes individuals to developing esophageal adenocarcinoma (EAC). We hypothesized that BE provides a unique environment for increased long-interspersed element 1 (LINE-1 or L1) retrotransposition. To this end, we evaluated 5 patients with benign BE, 5 patients with BE and concomitant EAC, and 10 additional patients with EAC to determine L1 activity in this progressive disease. After L1-seq, we confirmed 118 somatic insertions by PCR in 10 of 20 individuals. We observed clonal amplification of several insertions which appeared to originate in normal esophagus (NE) or BE and were later clonally expanded in BE or in EAC. Additionally, we observed evidence of clonality within the EAC cases; specifically, 22 of 25 EAC-only insertions were present identically in distinct regions available from the same tumor, suggesting that these insertions occurred in the founding tumor cell of these lesions. L1 proteins must be expressed for retrotransposition to occur; therefore, we evaluated the expression of open reading frame 1 protein (ORF1p), a protein encoded by L1, in eight of the EAC cases for which formalin-fixed paraffin embedded tissue was available. With immunohistochemistry, we detected ORF1p in all tumors evaluated. Interestingly, we also observed dim ORF1p immunoreactivity in histologically NE of all patients. In summary, our data show that somatic retrotransposition occurs early in many patients with BE and EAC and indicate that early events occurring even in histologically NE cells may be clonally expanded in esophageal adenocarcinogenesis. PMID:26283398

  19. Preoperative Chemoradiation Therapy in Combination With Panitumumab for Patients With Resectable Esophageal Cancer: The PACT Study

    SciTech Connect

    Kordes, Sil; Berge Henegouwen, Mark I. van; Hulshof, Maarten C.; Bergman, Jacques J.G.H.M.; Vliet, Hans J. van der; Kapiteijn, Ellen; Laarhoven, Hanneke W.M. van; Richel, Dick J.; Klinkenbijl, Jean H.G.; Meijer, Sybren L.; Wilmink, Johanna W.

    2014-09-01

    Purpose: Preoperative chemoradiation therapy (CRT) has become the standard treatment strategy for patients with resectable esophageal cancer. This multicenter phase 2 study investigated the efficacy of the addition of the epidermal growth factor receptor (EGFR) inhibitor panitumumab to a preoperative CRT regimen with carboplatin, paclitaxel, and radiation therapy in patients with resectable esophageal cancer. Methods and Materials: Patients with resectable cT1N1M0 or cT2-3N0 to -2M0 tumors received preoperative CRT consisting of panitumumab (6 mg/kg) on days 1, 15, and 29, weekly administrations of carboplatin (area under the curve [AUC] = 2), and paclitaxel (50 mg/m{sup 2}) for 5 weeks and concurrent radiation therapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Primary endpoint was pathologic complete response (pCR) rate. We aimed at a pCR rate of more than 40%. Furthermore, we explored the predictive value of biomarkers (EGFR, HER 2, and P53) for pCR. Results: From January 2010 until December 2011, 90 patients were enrolled. Patients were diagnosed predominantly with adenocarcinoma (AC) (80%), T3 disease (89%), and were node positive (81%). Three patients were not resected due to progressive disease. The primary aim was unmet, with a pCR rate of 22%. Patients with AC and squamous cell carcinoma reached a pCR of 14% and 47%, respectively. R0 resection was achieved in 95% of the patients. Main grade 3 toxicities were rash (12%), fatigue (11%), and nonfebrile neutropenia (11%). None of the biomarkers was predictive for response. Conclusions: The addition of panitumumab to CRT with carboplatin and paclitaxel was safe and well tolerated but could not improve pCR rate to the preset criterion of 40%.

  20. LINE-1 expression and retrotransposition in Barretts esophagus and esophageal carcinoma

    PubMed Central

    Doucet-O'Hare, Tara T.; Rodi?, Nemanja; Sharma, Reema; Darbari, Isha; Abril, Gabriela; Choi, Jungbin A.; Young Ahn, Ji; Cheng, Yulan; Anders, Robert A.; Burns, Kathleen H.; Meltzer, Stephen J.; Kazazian, Haig H.

    2015-01-01

    Barretts esophagus (BE) is a common disease in which the lining of the esophagus transitions from stratified squamous epithelium to metaplastic columnar epithelium that predisposes individuals to developing esophageal adenocarcinoma (EAC). We hypothesized that BE provides a unique environment for increased long-interspersed element 1 (LINE-1 or L1) retrotransposition. To this end, we evaluated 5 patients with benign BE, 5 patients with BE and concomitant EAC, and 10 additional patients with EAC to determine L1 activity in this progressive disease. After L1-seq, we confirmed 118 somatic insertions by PCR in 10 of 20 individuals. We observed clonal amplification of several insertions which appeared to originate in normal esophagus (NE) or BE and were later clonally expanded in BE or in EAC. Additionally, we observed evidence of clonality within the EAC cases; specifically, 22 of 25 EAC-only insertions were present identically in distinct regions available from the same tumor, suggesting that these insertions occurred in the founding tumor cell of these lesions. L1 proteins must be expressed for retrotransposition to occur; therefore, we evaluated the expression of open reading frame 1 protein (ORF1p), a protein encoded by L1, in eight of the EAC cases for which formalin-fixed paraffin embedded tissue was available. With immunohistochemistry, we detected ORF1p in all tumors evaluated. Interestingly, we also observed dim ORF1p immunoreactivity in histologically NE of all patients. In summary, our data show that somatic retrotransposition occurs early in many patients with BE and EAC and indicate that early events occurring even in histologically NE cells may be clonally expanded in esophageal adenocarcinogenesis. PMID:26283398

  1. Combined cis-platinum plus radiation antitumor activity in locoregionally advanced squamous cell esophageal cancer.

    PubMed

    Kolarić, K; Nagy, B; Roth, A; Zupanc, D; Luetić, J; Tometić, Z

    1988-01-01

    The synergistic activity we have observed in vitro in V-79 hamster lung cells after treatment with cis-platinum combined with irradiation, stimulated a pilot study of 31 patients with inoperable locoregionally advanced squamous cell esophageal cancer. The 27 evaluable cases (22 men and 5 women--mean age 59 years) had undergone no prior radiation or cytostatic drug therapy. Histological evidence of the tumor (26 squamous cell, 1 adenocarcinoma) was obtained by endoscopy in all patients before treatment began. The patients were irradiated in two opposite thoracic fields with a total dosage of 3,000-4,000 cGy (200 cGy daily, 1,000 weekly) concurrently with 2 cycles of cis-platinum in the dosage of 30 mg/m2 iv. daily X 4 (120 mg/m2 per cycle). The results showed that cis-platinum combined with radiation showed an evident antitumor activity which included 4 complete clinical remissions and 11 partial remissions with a response rate of 56% (15/27). In two complete responders even a pathologic remission was evident (biopsy specimen) and they are now 16+ and 18+ months free of the disease. The median remission duration has been 8+ months (14+ months in complete responders) and the median survival period for the entire group is 10+ months (for responders 15+ months, p less than 0.05). Toxicity was moderate and reversible, and mainly accounted for radiation mucositis, retrosternal pain and vomiting. A mild bone marrow suppression was observed. In 2 cases esophagotracheal fistulae occurred. The results of this study show that the combination of cis-platinum and radiation might constitute successful palliative or neoadjuvant treatment for squamous cell esophageal cancer. PMID:2455256

  2. Emerging techniques and efficacy of endoscopic esophageal reconstruction and lumen restoration for complete esophageal obstruction

    PubMed Central

    Perbtani, Yaseen; Suarez, Alejandro L.; Wagh, Mihir S.

    2016-01-01

    Background and study aims: Complete esophageal obstruction (CEO) is a rare occurrence characterized by progressive esophageal stricture, which eventually causes lumen obliteration. With recent advances in flexible endoscopy, various innovative techniques exist for restoring luminal continuity. The primary aim of this study was to assess the efficacy and safety of patients undergoing combined antegrade-retrograde endoscopic dilation for CEO at our institution. The secondary aim was to review and highlight emerging techniques, outcomes, and adverse events after endoscopic treatment of CEO. Patients and methods: Our electronic endoscopy database was retrospectively reviewed to identify patients who underwent combined antegrade and retrograde endoscopy for CEO. Patient and procedural data collected included gender, age, technical success, pre- and post-dysphagia scores, and adverse events. Results: Six patients (67 % male, mean age 71.6 years [range 63 – 80]) underwent technically successful esophageal reconstruction with combined antegrade-retrograde endoscopy. All patients noted improvement in dysphagia with mean pre-procedure dysphagia score of 4 reduced to 1.33 (range 0 – 3) post-procedure. There were no adverse events and mean follow-up time was 17.3 months (range 3 – 48). Conclusions: Combined antegrade and retrograde endoscopic therapy for CEO is feasible and safe. We present our experience with endoscopic management of complete esophageal obstruction, and highlight emerging techniques, outcomes and adverse events related to this minimally invasive modality. PMID:26878039

  3. Altered esophageal histamine receptor expression in Eosinophilic Esophagitis (EoE): implications on disease pathogenesis.

    PubMed

    Merves, Jamie; Chandramouleeswaran, Prasanna Modayur; Benitez, Alain J; Muir, Amanda B; Lee, Anna J; Lim, Diana M; Dods, Kara; Mehta, Isha; Ruchelli, Eduardo D; Nakagawa, Hiroshi; Spergel, Jonathan M; Wang, Mei-Lun

    2015-01-01

    Eosinophilic Esophagitis (EoE) is a chronic allergic disorder, whose pathobiology is incompletely understood. Histamine-producing cells including mast cells and basophils have been implicated in EoE. However, very little is currently known about the role of histamine and histamine receptor (HR) expression and signaling in the esophageal epithelium. Herein, we characterized HR (H1R, H2R, H3R, and H4R) expression in human esophageal biopsies and investigate the role of histamine signaling in inducible cytokine expression in human esophageal epithelial cells in vitro. HR expression was quantified in esophageal biopsies from non-EoE control (N = 23), inactive EoE (<15 eos/hpf, N = 26) and active EoE (>15 eos/hpf, N = 22) subjects using qRT-PCR and immunofluorescent localization. HR expression and histamine-mediated cytokine secretion were evaluated in human primary and telomerase-immortalized esophageal epithelial cells. H1R, H2R, and H4R expression were increased in active EoE biopsies compared to inactive EoE and controls. H2R was the most abundantly expressed receptor, and H3R expression was negligible in all 3 cohorts. Infiltrating eosinophils expressed H1R, H2R, and H4R, which contributed to the observed increase in HR in active subjects. H1R and H2R, but not H3R or H4R, were constitutively expressed by primary and immortalized cells, and epithelial histamine stimulation induced GM-CSF, TNFα, and IL-8, but not TSLP or eotaxin-3 secretion. Epithelial priming with the TLR3 ligand poly (I:C) induced H1R and H2R expression, and enhanced histamine-induced GM-CSF, TNFα, and IL-8 secretion. These effects were primarily suppressed by H1R antagonists, but unaffected by H2R antagonism. Histamine directly activates esophageal epithelial cytokine secretion in vitro in an H1R dependent fashion. However, H1R, H2R and H4R are induced in active inflammation in EoE in vivo. While systemic antihistamine (anti-H1R) therapy may not induce clinical remission in EoE, our study suggests that further study of histamine receptor signaling in EoE is warranted and that targeting of additional histamine receptors may lead to novel treatment strategies for this important disease. PMID:25723478

  4. Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line

    PubMed Central

    Niu, Chao; Chauhan, Uday; Gargus, Matthew; Shaker, Anisa

    2016-01-01

    Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies. PMID:27055018

  5. Serological identification of tumor antigens of esophageal squamous cell carcinoma.

    PubMed

    Shimada, Hideaki; Nakashima, Kazue; Ochiai, Takenori; Nabeya, Yoshihiro; Takiguchi, Masaki; Nomura, Fumio; Hiwasa, Takaki

    2005-01-01

    Autoantibodies are often detected in the patients with esophageal cancer. We applied serological analysis of recombinant cDNA expression libraries (SEREX) to a case of esophageal squamous cell carcinoma in order to identify tumor antigens. A cDNA library derived from an esophageal cancer cell line was bacterially expressed and screened for interaction with antibodies in five allogeneic sera of patients with esophageal squamous cell carcinoma. To examine the specific immunoreactivity of the antigens, sera from 16 more patients with esophageal squamous cell carcinoma, 16 patients with gastric cancer, 16 patients with colon cancer, 16 patients with breast cancer and 37 healthy volunteers were screened. We identified 11 independent cDNA clones that potentially encoded esophageal cancer tumor antigens. The identified cDNA clones were SURF1, HOOK2, CENP-F, ZIC2, hCLA-iso, Ki-1/57, enigma, HCA25a, SPK and two EST clones named LOC146223 and AGENCOURT_7565913. The sero-positive rates of antibodies against SURF1 (48%), LOC146223 (38%), HOOK2 (14%) and AGENCOURT_7565913 (14%) were significantly higher in esophageal cancer patients than in healthy controls. At least one of these antibodies was detected in 18 (86%) of 21 sera from esophageal cancer patients. A disease-specific humoral immune response against SURF1, LOC146223, HOOK2 or AGENCOURT_7565913 was observed in most patients with esophageal squamous cell carcinoma. Antibodies against these SEREX antigens may represent a pool of candidates for serum tumor markers of esophageal squamous cell carcinoma. PMID:15586227

  6. Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line.

    PubMed

    Niu, Chao; Chauhan, Uday; Gargus, Matthew; Shaker, Anisa

    2016-01-01

    Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies. PMID:27055018

  7. Thrombocytes Correlate with Lymphangiogenesis in Human Esophageal Cancer and Mediate Growth of Lymphatic Endothelial Cells In Vitro

    PubMed Central

    Schoppmann, Sebastian F.; Alidzanovic, Lejla; Schultheis, Andrea; Perkmann, Thomas; Brostjan, Christine; Birner, Peter

    2013-01-01

    Recent data provide evidence for an important role of thrombocytes in lymphangiogenesis within human malignant disease. The aim of this study was to investigate the role of thrombocytes in lymphangiogenesis in human esophageal cancer. Perioperative peripheral blood platelet counts (PBPC) were evaluated retrospectively in 320 patients with esophageal cancer, comprising 184 adenocarcinomas (AC), and 136 squamous cell carcinomas (SCC). Data on lymphangiogenesis evaluated by anti-podoplanin immunostaining were available from previous studies, platelets within the tumor tissue were assessed by CD61 immunostaining. For in vitro studies, human lymphatic endothelial cells (LECs) were isolated and co-cultured with peripheral blood platelets. Stromal thrombocytic clusters (STC) were evident in 82 samples (25.6%), and vascular thrombocytic clusters (VTC) in 56 (17.5%). STC and VTC were associated with a significantly higher PBPC at investigation of all cases. The presence of STC was associated with higher lymphatic microvessel density (p<0.001), PBPC and STC were associated with lymphovascular invasion of tumor cells in a regression model. The presence of STCs was associated with shorter DFS of all patients (p = 0.036, Breslow test), and VTC with shorter DFS in in SCC (p = 0.025, Breslow test). In cell culture, LEC proliferation was enhanced by co-culture with human platelets in a dose- and time-dependent manner mediated by the release of PDGF-BB and VEGF-C. Platelets play an important role in lymphangiogenesis and lymphovascular invasion in esophageal cancer, influencing prognosis. So the disruption of signaling pathways between platelets, tumor cells and lymphatic endothelium might be of benefit for patients. PMID:23840559

  8. Upper esophageal sphincter during transient lower esophageal sphincter relaxation: effects of reflux content and posture

    PubMed Central

    Babaei, Arash; Bhargava, Valmik

    2010-01-01

    Although some studies show that the upper esophageal sphincter (UES) contracts during transient lower esophageal sphincter relaxation (TLESR), others show that it relaxes. We hypothesized that the posture of the subject and constituents of gastroesophageal reflux (GER) may determine the type of UES response during the TLESR. High-resolution manometry and esophageal pH/impedance recording were performed in 10 healthy volunteers in the right recumbent (1 h) and upright (1 h) positions following the ingestion of a 1,000-Kcal meal. The UES pressure response during TLESR and constituents of GER (liquid, air, and pH) were determined. 109 TLESRs (58 upright and 51 recumbent) were analyzed. The majority of TLESRs were associated with GER (91% upright and 88% recumbent) events. UES relaxation was the predominant response during upright position (81% of TLESRs), and it was characteristically associated with presence of air in the reflux (92%). On the other hand, UES contraction was the predominant response during recumbent position (82% of TLESRs), and it was mainly associated with liquid reflux (71%). The rate of esophageal pressure increase (dP/dt) during the GER, but not the pH, had major influence on the type of UES response during TLESR. The dP/dt during air reflux (127 ± 39 mmHg/s) was significantly higher than liquid reflux (31 ± 6 mmHg/s, P < 0.0001). We concluded that the nature of UES response during TLESR, relaxation or contraction, is related to the posture and the constituents of GER. We propose that the rapid rate of esophageal pressure increase associated with air reflux determines the UES relaxation response to GER. PMID:20167874

  9. Fusion of human bone hemopoietic stem cell with esophageal carcinoma cells didn't generate esophageal cancer stem cell.

    PubMed

    Fan, H; Lu, S

    2014-01-01

    Prior studies showed that cell fusion between bone marrow-derived cell (BMDC) and somatic cell might be the origin of cancer stem cell. Our previous study suggested that cell fusion of human bone marrow-derived mesenchymal stem cell (MSC) with esophageal cancer cell did not generate cancer stem cells. But up to now, the origin of cancer stem cell is still ambiguous. In this study, we carried out the cell fusion experiment between hemopoietic stem cells (HSCs) and human esophageal cancer cells, and found that cell fusion slowed the growth speed of esophageal cancer cells and decreased the clone formation ability and tumorigenicity in NOD/SCID mice. In addition, cell fusion did not increase the ratio of side population (SP) cells and the resistance to chemotherapeutic drugs. Collectively, our data indicated that cell fusion between HSCs and esophageal cancer cells has a therapeutic effect rather than generate cells with characteristics of esophageal cancer stem cells. PMID:25030437

  10. Topical protection of human esophageal mucosal integrity.

    PubMed

    Woodland, P; Batista-Lima, F; Lee, C; Preston, S L; Dettmar, P; Sifrim, D

    2015-06-15

    Patients with nonerosive reflux disease exhibit impaired esophageal mucosal integrity, which may underlie enhanced reflux perception. In vitro topical application of an alginate solution can protect mucosal biopsies against acid-induced changes in transepithelial electrical resistance (TER). We aimed to confirm this finding in a second model using 3D cell cultures and to assess prolonged protection in a biopsy model. We assessed the protective effect of a topically applied alginate solution 1 h after application. 3D cell cultures were grown by using an air-liquid interface and were studied in Ussing chambers. The apical surface was "protected" with 200 μl of either alginate or viscous control or was unprotected. The tissue was exposed to pH 3 + bile acid solution for 30 min and TER change was calculated. Distal esophageal mucosal biopsies were taken from 12 patients and studied in Ussing chambers. The biopsies were coated with either alginate or viscous control solution. The biopsies were then bathed in pH 7.4 solution for 1 h. The luminal chamber solution was replaced with pH 2 solution for 30 min. Percentage changes in TER were recorded. In five biopsies fluorescein-labeled alginate solution was used to allow immunohistological localization of the alginate after 1 h. In the cell culture model, alginate solution protected tissue against acid-induced change in TER. In biopsies, 60 min after protection with alginate solution, the acidic exposure caused a -8.3 ± 2.2% change in TER compared with -25.1 ± 4.5% change after protection with the viscous control (P < 0.05). Labeled alginate could be seen coating the luminal surface in all cases. In vitro, alginate solutions can adhere to the esophageal mucosa for up to 1 h and exert a topical protectant effect. Durable topical protectants can be further explored as first-line/add-on therapies for gastroesophageal reflux disease. PMID:25907692

  11. Esophageal Squamous Cell Carcinoma Patients Have an Increased Risk of Coexisting Colorectal Neoplasms

    PubMed Central

    Baeg, Myong Ki; Choi, Myung-Gyu; Jung, Yun Duk; Ko, Sun-Hye; Lim, Chul-Hyun; Kim, Hyung Hun; Kim, Jin Su; Cho, Yu Kyung; Park, Jae Myung; Lee, In Seok; Kim, Sang-Woo

    2016-01-01

    Background/Aims Esophageal squamous cell carcinoma (ESCC) and colorectal neoplasms (CRNs) share risk factors. We aimed to investigate whether the CRN risk is increased in ESCC patients. Methods ESCC patients who underwent a colonoscopy within 1 year of diagnosis were retrospectively analyzed. Patients were matched 1:3 by age, gender, and body mass index to asymptomatic controls. CRN was defined as the histological confirmation of adenoma or adenocarcinoma. Advanced CRN was defined as any of the following: ≥3 adenomas, high-grade dysplasia, villous features, tumor ≥1 cm, or adenocarcinoma. The risk factors for both CRN and advanced CRN were evaluated by univariate and multivariate analyses. Results Sixty ESCC patients were compared with 180 controls. The ESCC group had significantly higher numbers of CRNs (odds ratio [OR], 2.311; 95% confidence interval [CI], 1.265 to 4.220; p=0.006) and advanced CRNs (OR, 2.317; 95% CI, 1.185 to 4.530; p=0.013). Significant risk factors for both CRN and advanced CRN by multivariate analysis included ESCC (OR, 2.157, 95% CI, 1.106 to 4.070, p=0.024; and OR, 2.157, 95% CI, 1.045 to 4.454, p=0.038, respectively) and older age (OR, 1.068, 95% CI, 1.032 to 1.106, p<0.001; and OR, 1.065, 95% CI, 1.024 to 1.109, p=0.002, respectively). Conclusions The rates of CRN and advanced CRN are significantly increased in ESCC. Colonos-copy should be considered at ESCC diagnosis. PMID:25963088

  12. Emerging Therapeutic Options for Eosinophilic Esophagitis

    PubMed Central

    Dougherty, Timothy; Stephen, Sindu; Borum, Marie L.

    2014-01-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus that often occurs in atopic persons. Management strategies include pharmacotherapy, dietary modification, and endoscopic therapy, although patients will often have a relapsing and remitting course. Currently, the primary pharmacotherapy for EoE consists of corticosteroids. Immuno-modulators, leukotriene antagonists, biologies, and monoclonal antibodies are currently under study for treatment of EoE. The role of immunoglobulin E-mediated allergic reactions has been well documented and may provide insight into the etiology and effective therapy of EoE. PMID:24803874

  13. Unusual esophageal foreign body: a table fork.

    PubMed

    Mevio, Emilio; Mevio, Niccol

    2013-01-01

    The presence of an esophageal foreign body (EFB) is a medical emergency requiring urgent evaluation and treatment. Swallowing of foreign bodies is most common in children aged between 6 months and 6 years, in whom it usually occurs during games. In adults, foreign bodies tend to be ingested accidentally together with food. The authors report an unusual case of EFB (a table fork) in an adult and briefly report the clinical presentation and the therapeutic procedures adopted in this case and similar cases. PMID:23634316

  14. DNA Methylation Changes in Atypical Adenomatous Hyperplasia, Adenocarcinoma In Situ, and Lung Adenocarcinoma

    PubMed Central

    Selamat, Suhaida A.; Galler, Janice S.; Joshi, Amit D.; Fyfe, M. Nicky; Campan, Mihaela; Siegmund, Kimberly D.; Kerr, Keith M.; Laird-Offringa, Ite A.

    2011-01-01

    Background Aberrant DNA methylation is common in lung adenocarcinoma, but its timing in the phases of tumor development is largely unknown. Delineating when abnormal DNA methylation arises may provide insight into the natural history of lung adenocarcinoma and the role that DNA methylation alterations play in tumor formation. Methodology/Principal Findings We used MethyLight, a sensitive real-time PCR-based quantitative method, to analyze DNA methylation levels at 15 CpG islands that are frequently methylated in lung adenocarcinoma and that we had flagged as potential markers for non-invasive detection. We also used two repeat probes as indicators of global DNA hypomethylation. We examined DNA methylation in 249 tissue samples from 93 subjects, spanning the putative spectrum of peripheral lung adenocarcinoma development: histologically normal adjacent non-tumor lung, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS, formerly known as bronchioloalveolar carcinoma), and invasive lung adenocarcinoma. Comparison of DNA methylation levels between the lesion types suggests that DNA hypermethylation of distinct loci occurs at different time points during the development of lung adenocarcinoma. DNA methylation at CDKN2A ex2 and PTPRN2 is already significantly elevated in AAH, while CpG islands at 2C35, EYA4, HOXA1, HOXA11, NEUROD1, NEUROD2 and TMEFF2 are significantly hypermethylated in AIS. In contrast, hypermethylation at CDH13, CDX2, OPCML, RASSF1, SFRP1 and TWIST1 and global DNA hypomethylation appear to be present predominantly in invasive cancer. Conclusions/Significance The gradual increase in DNA methylation seen for numerous loci in progressively more transformed lesions supports the model in which AAH and AIS are sequential stages in the development of lung adenocarcinoma. The demarcation of DNA methylation changes characteristic for AAH, AIS and adenocarcinoma begins to lay out a possible roadmap for aberrant DNA methylation events in tumor development. In addition, it identifies which DNA methylation changes might be used as molecular markers for the detection of preinvasive lesions. PMID:21731750

  15. FRY site-specific methylation differentiates pancreatic ductal adenocarcinoma from other adenocarcinomas.

    PubMed

    Srisuttee, Ratakorn; Ota, Jun; Muangsub, Tachapol; Keelawat, Somboon; Trirattanachat, Surang; Kitkumthorn, Nakarin; Mutirangura, Apiwat

    2016-06-01

    Adenocarcinoma is a type of cancer that occurs in the glandular cells throughout the body. There are several metastatic adenocarcinoma of unknown primary origin. Currently, there is no highly effective method to differentiate pancreatic ductal adenocarcinoma (PDAC) from other adenocarcinomas. Here, we identified pancreas tissue by site-specific methylation at FRY and found that it can also detect PDAC. The establishment of Combined Bisulphite Restriction Analysis (COBRA) and quantitative real-time PCR techniques of FRY revealed FRY hypermethylation in 21 out of 24 normal pancreatic tissue samples, whereas all other normal tissue samples from thirteen other organs (80 samples) remained totally unmethylated. Similarly in application to PDAC, this marker effectively indicated 25 PDAC among 151 other common adenocarcinomas with values of 100%, 98.7%, 92.6%, and 100% in sensitivity, specificity, positive predictive value and negative predictive value, respectively. In summary, we have demonstrated that this epigenetic site-specific marker has high potential for pancreatic tissue identification and can be applied in PDAC diagnosis. PMID:26990916

  16. Clinical and endoscopic characteristics of drug-induced esophagitis

    PubMed Central

    Kim, Su Hwan; Jeong, Ji Bong; Kim, Ji Won; Koh, Seong-Joon; Kim, Byeong Gwan; Lee, Kook Lae; Chang, Mee Soo; Im, Jong Pil; Kang, Hyoun Woo; Shin, Cheol Min

    2014-01-01

    AIM: To investigate clinical, endoscopic and pathological characteristics of drug-induced esophagitis. METHODS: Data for patients diagnosed with drug-induced esophagitis from April 2002 to May 2013 was reviewed. Patients diagnosed with malignancy, viral or fungal esophagitis were excluded. Clinical, endoscopic and pathological characteristics of patients diagnosed with drug-induced esophagitis were analyzed. RESULTS: Seventy-eight patients were diagnosed with drug-induced esophagitis. Their mean age was 43.9 ± 18.9 years and 35.9% were male. Common symptoms were chest pain (71.8%), odynophagia (38.5%) and dysphagia (29.5%). The endoscopic location was in the middle third of esophagus in 78.2%. Endoscopic findings were ulcer (82.1%), erosion (17.9%), ulcer with bleeding (24.4%), coating with drug material (5.1%), impacted pill fragments (3.8%) and stricture (2.6%). Kissing ulcers were observed in 43.6%. The main causative agents were antibiotics and non-steroidal anti-inflammatory drugs. All the patients were treated with proton pump inhibitors (PPIs) or sucralfate, and the causative drugs were discontinued. Nineteen patients with drug-induced esophagitis were followed up with endoscopy and revealed normal findings, scars or healing ulcers. CONCLUSION: Drug-induced esophagitis mainly presents as chest pain, odynophagia and dysphagia, and may be successfully treated with PPIs and discontinuation of the causative drug. Kissing ulcers were observed in 43.6%. PMID:25152603

  17. Esophageal obstruction in horses: a retrospective study of 34 cases.

    PubMed Central

    Feige, K; Schwarzwald, C; Fürst, A; Kaser-Hotz, B

    2000-01-01

    The major purpose of this investigation was to describe the causes, possible complications, and prognoses of horses with esophageal obstruction. Of 34 cases presenting with esophageal obstruction, 28 cases were due to impaction of ingesta. Obstruction due to pre-existing esophageal disease occurred in 4 horses with megaesophagus, in 1 horse with stricture in the upper third of the esophagus, and in 1 horse with esophageal diverticulum. There was no significant difference in the contamination of the trachea between horses that subsequently developed aspiration pneumonia and those that did not. The duration of esophageal obstruction prior to admission was significantly longer in horses that developed aspiration pneumonia (median 18, range 2-48 h) than in those horses that did not (median 4, range 0.5-48 h). Although the obstruction was relieved in all 34 horses, 4 were euthanized because of recurring obstruction due to megaesophagus (n = 2), esophageal diverticulum (n = 1), and esophageal stricture (n = 1). Images Figure 1. Figure 2. Figure 3. PMID:10738598

  18. Choroidal and cutaneous metastasis from gastric adenocarcinoma.

    PubMed

    Kawai, Shoichiro; Nishida, Tsutomu; Hayashi, Yoshito; Ezaki, Hisao; Yamada, Takuya; Shinzaki, Shinichiro; Miyazaki, Masanori; Nakai, Kei; Yakushijin, Takayuki; Watabe, Kenji; Iijima, Hideki; Tsujii, Masahiko; Nishida, Kohji; Takehara, Tetsuo

    2013-03-01

    Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions. PMID:23538460

  19. Gall bladder Adenocarcinoma in a Young Girl.

    PubMed

    Date, Shivprasad V; Rizvi, S J

    2015-04-01

    A 16-year-old girl presented with abdominal discomfort, weakness, and jaundice. General examination revealed deep icterus with hard lymph nodes in left supraclavicular region. On gastrointestinal examination, we appreciated a hard intra-abdominal lump in the right hypochondrium. Biochemical evaluation showed features of obstructive jaundice. Imaging confirmed the presence of gall bladder lump with multiple intra-abdominal lymph nodes. Fine needle aspiration cytology of neck nodes demonstrated metastatic adenocarcinoma. Fine needle aspiration cytology of the gall bladder lump (done under sonographic guidance) confirmed poorly differentiated adenocarcinoma. To the best of our knowledge, malignancy of the gall bladder has not been reported in individuals less than 18 years in India, and only three cases have been reported worldwide in English literature. PMID:26139973

  20. Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis.

    PubMed

    Masri, Selma; Papagiannakopoulos, Thales; Kinouchi, Kenichiro; Liu, Yu; Cervantes, Marlene; Baldi, Pierre; Jacks, Tyler; Sassone-Corsi, Paolo

    2016-05-01

    The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous "zeitgebers," such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here, we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK, and SREBP signaling, leading to altered insulin, glucose, and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver. PAPERCLIP. PMID:27153497