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Sample records for esophageal adenocarcinoma ea

  1. Cutaneous Metastases From Esophageal Adenocarcinoma

    PubMed Central

    Triantafyllou, Stamatina; Georgia, Doulami; Gavriella-Zoi, Vrakopoulou; Dimitrios, Mpistarakis; Stulianos, Katsaragakis; Theodoros, Liakakos; Georgios, Zografos; Dimitrios, Theodorou

    2015-01-01

    The aim of this study is to present 2 rare cases of cutaneous metastases originated from adenocarcinoma of the gastro-esophageal junction, thus, underline the need for early diagnosis and possible treatment of suspicious skin lesions among patients with esophageal malignancy. Metastatic cancer to the skin originated from internal malignancies, mostly lung cancer, breast cancer, and colorectal cancer, constitute 0.5 to 9% of all metastatic cancers.5,8,15 Skin metastases, mainly from squamous cell carcinomas of the esophagus, are rarely reported. Cutaneous metastasis is a finding indicating progressiveness of the disease.17 More precisely, median survival is estimated approximately 4.7 months.2,14 This study is a retrospective review of 2 cases of patients with adenocarcinoma of the esophagus and a review of the literature. Two patients aged 60 and 32 years old, respectively, underwent esophagectomy. Both pathologic reports disclosed adenocarcinoma of the gastro-esophageal junction staged T3 N2 M0 (stage IIIB). During follow-up time, the 2 patients were diagnosed with cutaneous metastases originated from the primary esophageal tumor 11 and 4 months after surgery, respectively. The first patient is alive 37 months after diagnosis, while the second one died 16 months after surgery. Cutaneous metastasis caused by esophageal adenocarcinoma is possible. Therefore, follow-up of patients who were diagnosed with esophageal malignancy and underwent esophagectomy is mandatory in order to reveal early surgical stages. PMID:25785344

  2. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

    2016-01-01

    Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention. PMID:27331918

  3. Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma.

    PubMed

    Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng

    2016-02-01

    Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett's esophagus [BE]) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done, but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (ie, changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia-EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel therapeutic

  4. Microbiome and potential targets for chemoprevention of esophageal adenocarcinoma.

    PubMed

    Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng

    2016-02-01

    Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett's esophagus [BE]) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done, but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (ie, changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia-EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel therapeutic

  5. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-09-15

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

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

    PubMed Central

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

    2011-01-01

    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 BE, 18 cases of low grade dysplasia and 15 cases of high grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and CISH 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 CISH and high density microarrays. We further confirm the similar frequency of HER2 amplification by CISH (18.10%; 21/116) and SNP 6.0 microarrays (16.4%, 19/116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12.1 % (14/116) of esophageal adenocarcinoma and 6.67% (1/15) of HGD. No HER2 amplification or overexpression was identified in BE or LGD. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by CISH than protein overexpression in esophageal adenocarcinoma (18.10% vs 12.9%). A modified two-step model for esophageal adenocarcinoma HER-2 testing is recommend for clinical esophageal adenocarcinoma HER-2 trial. PMID:21460800

  7. 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.

  8. Endoscopic assessment and management of early esophageal adenocarcinoma.

    PubMed

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

    2014-08-15

    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

  9. 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

  10. Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett’s Esophagus, and Gastroesophageal Reflux

    PubMed Central

    2013-01-01

    Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett’s esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were two-sided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10−9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10−7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10−6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. PMID:24168968

  11. 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

  12. 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.

  13. 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

  14. 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

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

    PubMed

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

    2015-10-01

    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

  17. Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma

    PubMed Central

    Runge, Thomas M.; Abrams, Julian A.; Shaheen, Nicholas J.

    2015-01-01

    Barrett’s esophagus (BE) is a common condition, and is the precursor to esophageal adenocarcinoma, a disease with increasing burden in the western world, especially in Caucasian males. The incidence of BE increased dramatically during the late-20th century and incidence estimates continue to increase, with a prominent male:female ratio. The prevalence is between 0.5 – 2.0 percent. A number of anthropomorphic and behavioral risk factors exist for BE including obesity and tobacco smoking, but GERD is the strongest risk factor, and the risk is more pronounced with long-standing GERD. Esophageal adenocarcinoma (EAC) is the most common form of esophageal cancer in the U.S. Risk factors include GERD, tobacco smoking, and obesity, while NSAIDs and statins may be protective. A major factor predicting progression from non-dysplastic BE to EAC is the presence of dysplastic changes seen on esophageal histology, although a number of issues limit the utility of dysplasia as a marker for disease. Length of the involved BE segment is another risk for progression to high-grade dysplasia and cancer. Biomarkers have shown promise, but none are approved for clinical use. PMID:26021191

  18. Biomarkers in Barrett’s esophagus and esophageal adenocarcinoma: Predictors of progression and prognosis

    PubMed Central

    Ong, Chin-Ann J; Lao-Sirieix, Pierre; Fitzgerald, Rebecca C

    2010-01-01

    Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application. PMID:21128316

  19. Genetic and Epigenetic Alterations in Barrett's Esophagus and Esophageal Adenocarcinoma.

    PubMed

    Kaz, Andrew M; Grady, William M; Stachler, Matthew D; Bass, Adam J

    2015-06-01

    Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), wherein normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. BE can progress to low- and high-grade dysplasia, intramucosal, and invasive carcinoma. Both BE and EAC are characterized by loss of heterozygosity, aneuploidy, specific genetic mutations, and clonal diversity. Given the limitations of histopathology, genomic and epigenomic analyses may improve the precision of risk stratification. Assays to detect molecular alterations associated with neoplastic progression could be used to improve the pathologic assessment of BE/EAC and to select high-risk patients for more intensive surveillance. PMID:26021206

  20. Mechanisms of esophageal adenocarcinoma formation and approaches to chemopreventive intervention.

    PubMed

    Richmond, Ellen; Umar, Asad

    2016-02-01

    The incidence of esophageal adenocarcinoma (EAC), a debilitating and highly lethal malignancy, has risen dramatically over the past 40 years in the United States and other Western countries. To reverse this trend, EAC prevention and early detection efforts by clinicians, academic researchers and endoscope manufacturers have targeted Barrett's esophagus (BE), the widely accepted EAC precursor lesion. Data from surgical, endoscopic and pre-clinical investigations strongly support the malignant potential of BE. For patients with BE, the risk of developing EAC has been estimated at 11- to 125-fold greater than that of the individual at average risk. Nevertheless, screening for BE in symptomatic patients (ie, with symptoms of reflux) and surveillance in patients diagnosed with BE have not had a substantial impact on the incidence, morbidity or mortality of EAC; the overwhelming majority of EAC patients are diagnosed without a pre-operative diagnosis of BE. This article will discuss the current state of the science of esophageal adenocarcinoma prevention, including ideas about carcinogenesis and its underlying genomic and molecular level mechanisms, and suggest strategies for a systems approach to targeted preventive management. PMID:26970126

  1. Comparative genomic analysis of esophageal adenocarcinoma and squamous cell carcinoma.

    PubMed

    Agrawal, Nishant; Jiao, Yuchen; Bettegowda, Chetan; Hutfless, Susan M; Wang, Yuxuan; David, Stefan; Cheng, Yulan; Twaddell, William S; Latt, Nyan L; Shin, Eun J; Wang, Li-Dong; Wang, Liang; Yang, Wancai; Velculescu, Victor E; Vogelstein, Bert; Papadopoulos, Nickolas; Kinzler, Kenneth W; Meltzer, Stephen J

    2012-10-01

    Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12 esophageal squamous cell carcinomas (ESCC) from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (P < 0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett esophagus. These discoveries highlight key genetic differences between EACs and ESCCs and between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from Barrett esophagus.

  2. Esophageal Adenocarcinoma: The Influence of Medications Used to Treat Comorbidities on Cancer Prognosis.

    PubMed

    Thrift, Aaron P

    2015-12-01

    Esophageal adenocarcinoma has undergone a continuous rise in incidence since the early 1970s and is the fastest rising cancer among white men in the United States. Epidemiologic studies have demonstrated that medications commonly used to treat multiple chronic conditions (for example, aspirin, non-aspirin nonsteroidal anti-inflammatory drugs, and statins) as well as powerful acid suppressants such as proton pump inhibitors are associated with a reduced risk of esophageal adenocarcinoma. The chemopreventive potential of these classes of medications appears to be especially applicable to persons with Barrett's esophagus, the only known premalignant condition for esophageal adenocarcinoma. However, it is not known whether these medications also influence cancer recurrence and cancer-specific mortality in persons diagnosed with esophageal adenocarcinoma. This is an important question because most patients with esophageal adenocarcinoma have 1 or more comorbid conditions at the time of their cancer diagnosis and are receiving medication to treat these conditions. This article summarizes the evidence on the associations between 4 commonly used classes of medications and (1) risk of developing esophageal adenocarcinoma and Barrett's esophagus and (2) risk of cancer recurrence and cancer-specific mortality in patients with esophageal adenocarcinoma. PMID:25835331

  3. Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy

    PubMed Central

    Kumar, Sacheen; Abbassi-Ghadi, Nima; Salm, Max; Mitter, Richard; Horswell, Stuart; Rowan, Andrew; Phillimore, Benjamin; Biggs, Jennifer; Begum, Sharmin; Matthews, Nik; Hochhauser, Daniel; Hanna, George B; Swanton, Charles

    2015-01-01

    Esophageal adenocarcinomas (EACs) are associated with dismal prognosis. Deciphering the evolutionary histories of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable EACs, before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of EACs with the presence of heterogeneous driver mutations, parallel evolution, early genome doubling events and an association between high intratumor heterogeneity and poor response to NAC. Multi-region sequencing demonstrated a significant reduction in T>G mutations within a CTT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of C>A mutations within a CpC context following NAC. EACs are characterized by early chromosomal instability leading to amplifications containing targetable oncogenes persisting through chemotherapy, providing a rationale for future therapeutic approaches. PMID:26003801

  4. Whole-genome sequencing of nine esophageal adenocarcinoma cell lines.

    PubMed

    Contino, Gianmarco; Eldridge, Matthew D; Secrier, Maria; Bower, Lawrence; Fels Elliott, Rachael; Weaver, Jamie; Lynch, Andy G; Edwards, Paul A W; Fitzgerald, Rebecca C

    2016-01-01

    Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines-ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4-all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC. PMID:27594985

  5. Whole-genome sequencing of nine esophageal adenocarcinoma cell lines

    PubMed Central

    Contino, Gianmarco; Eldridge, Matthew D.; Secrier, Maria; Bower, Lawrence; Fels Elliott, Rachael; Weaver, Jamie; Lynch, Andy G.; Edwards, Paul A.W.; Fitzgerald, Rebecca C.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines—ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4—all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC. PMID:27594985

  6. Whole-genome sequencing of nine esophageal adenocarcinoma cell lines

    PubMed Central

    Contino, Gianmarco; Eldridge, Matthew D.; Secrier, Maria; Bower, Lawrence; Fels Elliott, Rachael; Weaver, Jamie; Lynch, Andy G.; Edwards, Paul A.W.; Fitzgerald, Rebecca C.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines—ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4—all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC.

  7. Distal Esophageal Adenocarcinoma and Gastric Adenocarcinoma: Time for a Shared Research Agenda.

    PubMed

    Jansen, Marnix; Wright, Nicholas A

    2016-01-01

    The key insight that sparked Darwin's theory of descent with modification was that he compared and contrasted differences between living and extinct species across time and space. He likely arrived on this theory in large part through his culinary experiences, set against the background of the rugged Patagonian landscape of Southern Argentina. We feel that further integration of research into gastric and esophageal adenocarcinoma may benefit both fields and similarly lead to a coherent understanding of cancer progression in the upper gastrointestinal tract across time and space. Although the environmental trigger differs between carcinogenesis of the stomach and distal esophagus, there remain many important lessons to be learned from comparing precursor stages, such as intestinal metaplasia, across anatomic borders. This analysis will absolutely require detailed sampling within and between these related species, but most importantly we need higher resolution clinical phenotyping to relate genomic differences to drivers of morphologic evolution. In the end, this may provide us with a new phylogeny showing key differences between esophageal and gastric adenocarcinoma. PMID:27573764

  8. 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

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

    PubMed

    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.

  10. Metastatic Gastrointestinal Adenocarcinoma with Osteoblastic Activity: A Case Report of Esophageal and Colonic Primaries

    PubMed Central

    Shabaik, Ahmed S.

    2016-01-01

    Adenocarcinoma with osteoblastic metastases is classically seen in prostate, breast, and lung primaries. Less common primary sites include thyroid, kidney, and stomach. We present two cases of primary gastrointestinal adenocarcinoma with metastatic osteoblastic activity from two previously unreported sites. The first case represents an esophageal adenocarcinoma arising in a background of intestinal metaplasia that metastasized with osteoblastic activity to the deltoid muscle. The second case demonstrates a Stage IV sigmoid colon adenocarcinoma with osteoblastic metastases to the liver and lymph nodes. The findings indicate that metastases from various gastrointestinal primary adenocarcinomas can have prominent bone formation. PMID:27738541

  11. Comprehensive Genomic Profiling of Advanced Esophageal Squamous Cell Carcinomas and Esophageal Adenocarcinomas Reveals Similarities and Differences

    PubMed Central

    Johnson, Adrienne; Ali, Siraj M.; Klempner, Samuel J.; Bekaii-Saab, Tanios; Vacirca, Jeffrey L.; Khaira, Depinder; Yelensky, Roman; Chmielecki, Juliann; Elvin, Julia A.; Lipson, Doron; Miller, Vincent A.; Stephens, Philip J.; Ross, Jeffrey S.

    2015-01-01

    Background. Esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EACs) account for >95% of esophageal malignancies and represent a major global health burden. ESCC is the dominant histology globally but represents a minority of U.S. cases, with EAC accounting for the majority of U.S. cases. The patient outcomes for advanced ESCC and EAC are poor, and new therapeutic options are needed. Using a sensitive sequencing assay, we compared the genomic profiles of ESCC and EAC with attention to identification of therapeutically relevant genomic alterations. Methods. Next-generation sequencing-based comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation-based libraries to a median coverage depth of >650× for all coding exons of 315 cancer-related genes plus selected introns from 28 genes frequently rearranged in cancer. Results from a single sample were evaluated for all classes of genomic alterations (GAs) including point mutations, short insertions and deletions, gene amplifications, homozygous deletions, and fusions/rearrangements. Clinically relevant genomic alterations (CRGAs) were defined as alterations linked to approved drugs and those under evaluation in mechanism-driven clinical trials. Results. There were no significant differences by sex for either tumor type, and the median age for all patients was 63 years. All ESCCs and EACs were at an advanced stage at the time of sequencing. All 71 ESCCs and 231 EACs featured GAs on profiling, with 522 GAs in ESCC (7.4 per sample) and 1,303 GAs in EAC (5.6 per sample). The frequency of clinically relevant GAs in ESCC was 94% (2.6 per sample) and 93% in EAC (2.7 per sample). CRGAs occurring more frequently in EAC included KRAS (23% EAC vs. 6% ESCC) and ERBB2 (23% EAC vs. 3% ESCC). ESCC samples were enriched for CRGA in PIK3CA (24% ESCC vs. 10% EAC), PTEN (11% ESCC vs. 4% EAC), and NOTCH1 (17% ESCC vs. 3% EAC). Other GAs that differed significantly between histologic

  12. Studying Cancer Evolution in Barrett's Esophagus and Esophageal Adenocarcinoma.

    PubMed

    Paulson, Thomas G

    2016-01-01

    Technological advances in genome sequencing and copy number analysis have allowed researchers to catalog the wide variety of genomic alterations that occur across diverse cancer types. For most cancer types, the lack of high-frequency alterations and the heterogeneity observed both within and between tumors suggest neoplastic progression proceeds through a branched evolutionary pathway as proposed by Nowell in 1976, as opposed to the linear pathway that has dominated medical science for the last century. To understand how cancer evolves over time and space in the body, new study designs are needed that can distinguish between alterations that develop in patients who progress to cancer from to those who don't. Here we present approaches developed in the study of Barrett's esophagus, a premalignant precursor of esophageal adenocarcinoma, and discuss strategies for applying the results from these analyses to address the critical clinical problems of overdiagnosis of benign disease, early detection of life-threatening cancer, and effective risk stratification. PMID:27573774

  13. 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

  14. Impact of peritumoral and intratumoral budding in esophageal adenocarcinomas.

    PubMed

    Thies, Svenja; Guldener, Lars; Slotta-Huspenina, Julia; Zlobec, Inti; Koelzer, Viktor H; Lugli, Alessandro; Kröll, Dino; Seiler, Christian A; Feith, Marcus; Langer, Rupert

    2016-06-01

    Tumor budding has prognostic significance in many carcinomas and is defined as the presence of detached isolated single cells or small cell clusters up to 5 cells at the invasion front (peritumoral budding [PTB]) or within the tumor (intratumoral budding [ITB]). For esophageal adenocarcinomas (EACs), there are currently only few data about the impact of this morphological feature. We investigated tumor budding in a large collective of 200 primarily resected EACs. Pancytokeratin staining was demonstrated to be superior to hematoxylin and eosin staining for the detection of buds with substantial to excellent interobserver agreement and used for subsequent analysis. PTB and ITB were scored across 10 high-power fields (HPFs). The median count of tumor buds was 130/10 HPFs for PTB (range, 2-593) and 80/10 HPFs for ITB (range, 1-656). PTB and ITB correlated significantly with each other (r = 0.9; P < .001). High PTB and ITB rates were seen in more advanced tumor categories (P < .001 each); tumors with lymph node metastases (P < .001/P = .002); and lymphatic, vascular, and perineural invasion and higher tumor grading (P < .001 each). Survival analysis showed an association with worse survival for high-grade ITB (P = .029) but not PTB (P = .385). However, in multivariate analysis, lymph node and resection status, but not ITB, were independent prognostic parameters. In conclusion, PTB and ITB can be observed in EAC to various degrees. High-grade budding is associated with aggressive tumor phenotype. Assessment of tumor budding, especially ITB, may provide additional prognostic information about tumor behavior and may be useful in specific cases for risk stratification of EAC patients. PMID:26980046

  15. 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

  16. First reports of esophageal adenocarcinoma with white globe appearance in Japanese and Caucasian patients

    PubMed Central

    Tonai, Yusuke; Ishihara, Ryu; Yamasaki, Yasushi; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Tomita, Yasuhiko; Iishi, Hiroyasu

    2016-01-01

    Background and study aims: Better endoscopic diagnosis in case of Barrett’s esophagus is still needed. White globe appearance (WGA) is a novel endoscopic marker for gastric adenocarcinoma, with high sensitivity for differentiating between gastric cancer/high-grade dysplasia and other lesions. We report 2 cases of esophageal adenocarcinoma with WGA. In Case 1, esophagogastroduodenoscopy (EGD) revealed a 10-mm esophageal adenocarcinoma in a 48-year-old Japanese woman with short-segment Barrett’s esophagus. A small (< 1 mm) white globular lesion, typical of WGA, was observed under the epithelium by magnifying narrow-band imaging. A dilated neoplastic gland with eosinophilic material and necrotic epithelial fragments was identified at the site of the WGA by histologic examination. In Case 2, EGD revealed a 5-mm esophageal adenocarcinoma in a 60-year-old Caucasian man with long-segment Barrett’s esophagus. A typical WGA was observed by magnifying narrow-band imaging and similar histologic findings were identified at the site of the WGA. WGA could be a reliable endoscopic finding for target biopsy in esophageal adenocarcinoma, if its specificity is as high as in gastric cancer. The clinical implications of WGA in patients with Barrett’s esophagus should be investigated further. PMID:27747281

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

    ClinicalTrials.gov

    2016-11-02

    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. Integrative post-genome-wide association analysis of CDKN2A and TP53 SNPs and risk of esophageal adenocarcinoma

    PubMed Central

    Buas, Matthew F.; Levine, David M.; Makar, Karen W.; Utsugi, Heidi; Onstad, Lynn; Li, Xiaohong; Galipeau, Patricia C.; Shaheen, Nicholas J.; Hardie, Laura J.; Romero, Yvonne; Bernstein, Leslie; Gammon, Marilie D.; Casson, Alan G.; Bird, Nigel C.; Risch, Harvey A.; Ye, Weimin; Liu, Geoffrey; Corley, Douglas A.; Blount, Patricia L.; Fitzgerald, Rebecca C.; Whiteman, David C.; Wu, Anna H.; Reid, Brian J.; Vaughan, Thomas L.

    2014-01-01

    Incidence of esophageal adenocarcinoma (EA) in Western countries has increased markedly in recent decades. Although several risk factors have been identified for EA and its precursor, Barrett’s esophagus (BE), including reflux, Caucasian race, male gender, obesity, and smoking, less is known about the role of inherited genetic variation. Frequent somatic mutations in the tumor suppressor genes CDKN2A and TP53 were recently reported in EA tumors, while somatic alterations at 9p (CDKN2A) and 17p (TP53) have been implicated as predictors of progression from BE to EA. Motivated by these findings, we used data from a genome-wide association study of 2515 EA cases and 3207 controls to analyze 37 germline single nucleotide polymorphisms at the CDKN2A and TP53 loci. Three CDKN2A polymorphisms were nominally associated (P < 0.05) with reduced risk of EA: rs2518720 C>T [intronic, odds ratio 0.90, P = 0.0121, q = 0.3059], rs3088440 G>A (3′UTR, odds ratio 0.84, P = 0.0186, q = 0.3059), and rs4074785 C>T (intronic, odds ratio 0.85, P = 0.0248, q = 0.3059). None of the TP53 single nucleotide polymorphisms reached nominal significance. Two of the CDKN2A variants identified were also associated with reduced risk of progression from BE to EA, when assessed in a prospective cohort of 408 BE patients: rs2518720 (hazard ratio 0.57, P = 0.0095, q = 0.0285) and rs3088440 (hazard ratio 0.34, P = 0.0368, q = 0.0552). In vitro functional studies of rs3088440, a single nucleotide polymorphism located in the seed sequence of a predicted miR-663b binding site, suggested a mechanism whereby the G>A substitution may attenuate miR-663b-mediated repression of the CDKN2A transcript. This study provides the first evidence that germline variation at the CDKN2A locus may influence EA susceptibility. PMID:25280564

  19. 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

  20. 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

  1. A cross sectional study of p504s, CD133, and Twist expression in the esophageal metaplasia dysplasia adenocarcinoma sequence.

    PubMed

    Ahmad, J; Arthur, K; Maxwell, P; Kennedy, A; Johnston, B T; Murray, L; McManus, D T

    2015-04-01

    The incidence of esophageal adenocarcinoma has increased dramatically over recent years and Barrett's esophagus is considered the most established risk factor for its development. Endoscopic surveillance of Barrett's esophagus is therefore recommended but hinges on histological interpretation of randomly taken biopsies which is poorly reproducible. The use of biomarkers presents an opportunity to improve our ability to risk-stratify these patients.We examined three biomarkers namely p504s, CD133, and Twist in the setting of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma to evaluate differential expression between benign, dysplastic, and malignant Barrett's tissue in an exploratory cross-sectional study. Twenty-five cases each of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma were included along-with 25 cases of esophagectomy resections for Barrett's adenocarcinoma. The biomarkers were immunostained on automated Ventana(®) immunostainer. The biopsies were assessed for biomarker expression by two independent observers. Granular cytoplasmic staining of p504s was observed in dysplastic Barrett's biopsies and esophageal adenocarcinoma but not in Barrett's esophagus. Apical and membranous CD133 expression was also observed in dysplastic Barrett's and esophageal adenocarcinoma. Nuclear Twist expression was seen predominantly in stromal cells. There was increased p504s expression in dysplastic Barrett's esophagus and esophageal adenocarcinoma compared with controls. CD133 expression was detected for the first time in esophageal adenocarcinoma and dysplastic Barrett's esophagus. Twist expression was not convincing enough to be labeled as Barrett's biomarker. p504s and CD133 have the potential to differentiate benign from malignant Barrett's tissue in this exploratory study. Their validity should be established in prospective longitudinal studies.

  2. Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Murphy, Caitlin C.; Correa, Arlene M.; Ajani, Jaffer A.; Komaki, Ritsuko U.; Welsh, James W.; Swisher, Stephen G.; Hofstetter, Wayne L.

    2016-01-01

    Background Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality eligible patients treated with definitive CXRT versus CXRT followed by esophagectomy. Methods We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival. Results Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR=2.041, 95% CI 1.235–3.373) and surgical resection (HR=0.504, 95% CI 0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50% and 54% risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 months vs. 20.3 months, p=0.012) and DFS (21.5 months vs. 11.4 months, p=0.007) were significantly improved with the addition of surgery compared to definitive CXRT. Conclusions Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease. PMID:23715646

  3. Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma

    PubMed Central

    Lehenkari, Petri P.; Saarnio, Juha; Karttunen, Tuomo J.; Kauppila, Joonas H.

    2016-01-01

    Background Toll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett's esophagus, dysplasia and esophageal adenocarcinoma. Methods TLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99). Results We found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett's mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis. Conclusions TLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma. PMID:27008696

  4. Role of epigenetic alterations in the pathogenesis of Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    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

  5. Loss of TGF-β Adaptor β2SP Activates Notch Signaling and SOX9 Expression in Esophageal Adenocarcinoma

    PubMed Central

    Song, Shumei; Maru, Dipen M.; Ajani, Jaffer A.; Chan, Chia-Hsin; Honjo, Soichiro; Lin, Hui-Kuan; Correa, Arlene; Hofstetter, Wayne L.; Davila, Marta; Stroehlein, John; Mishra, Lopa

    2013-01-01

    TGF-β and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-β signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-β adapter β2SP (SPNB2) activates Notch signaling and its target SOX9 in primary fibroblasts or esophageal adenocarcinoma cells. Expression of the stem cell marker SOX9 was markedly higher in esophageal adenocarcinoma tumor tissues than normal tissues, and its higher nuclear staining in tumors correlated with poorer survival and lymph node invasion in esophageal adenocarcinoma patients. Downregulation of β2SP by lentivirus short hairpin RNA increased SOX9 transcription and expression, enhancing nuclear localization for both active Notch1 (intracellular Notch1, ICN1) and SOX9. In contrast, reintroduction into esophageal adenocarcinoma cells of β2SP and a dominant-negative mutant of the Notch coactivator mastermind-like (dnMAN) decreased SOX9 promoter activity. Tumor sphere formation and invasive capacity in vitro and tumor growth in vivo were increased in β2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of β2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of β2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-β targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of β2SP switches TGF-β signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9. PMID:23536563

  6. Nucleic acid-sensing toll-like receptors 3, 7 and 8 in esophageal epithelium, barrett's esophagus, dysplasia and adenocarcinoma.

    PubMed

    Helminen, Olli; Huhta, Heikki; Lehenkari, Petri P; Saarnio, Juha; Karttunen, Tuomo J; Kauppila, Joonas H

    2016-05-01

    Toll-like receptors (TLRs) are immunological receptors recognizing various microbial and endogenous ligands, such as DNA, RNA, and other microbial and host components thus activating immunological responses. The expression of TLRs in esophageal adenocarcinoma is not well known. The aim of this study was to evaluate expression patterns of those TLRs that sense nucleic acids in Barrett's esophagus with and without dysplasia and in esophageal adenocarcinoma. TLRs 3, 7 and 8 were stained immunohistochemically and evaluated in a cohort of patients with esophageal adenocarcinoma or dysplasia. Specimens with normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37) and esophageal adenocarcinoma (n = 99) were studied. We used immunofluorescence to confirm the subcellular localization of TLRs. We found abundant expression of TLR3, 7 and 8 in esophageal squamous epithelium, columnar metaplasia, dysplasia and adenocarcinoma. Cytoplasmic expression of TLR3, TLR7 or TLR8 did not associate to clinicopathological parameters or prognosis in esophageal cancer. High nuclear expression of TLR8, confirmed with immunofluorescence, in cancer cells was observed in tumors of high T-stage (p < 0.01) and in tumors with organ metastasis (p < 0.001). High nuclear TLR8 expression was associated with poor prognosis (p < 0.001). The expression of TLR3, TLR7 and TLR8 increased toward dysplasia and adenocarcinoma. We demonstrated nuclear localization of TLR8, which associates with metastasis and poor prognosis. TLR3 and TLR7 do not seem to have prognostic significance in esophageal adenocarcinoma. PMID:27467941

  7. 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

  8. 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

  9. Magnifying endoscopy with narrow-band imaging findings in the diagnosis of Barrett's esophageal adenocarcinoma spreading below squamous epithelium.

    PubMed

    Omae, Masami; Fujisaki, Junko; Shimizu, Tomoki; Igarashi, Masahiro; Yamamoto, Noriko

    2013-05-01

    It has been described that most cases of Barrett's esophageal adenocarcinoma in Japan are cases of Barrett's esophageal adenocarcinoma on a background of short-segment Barrett's esophagus, frequently occurring rostrad to Barrett's epithelium, adjacent to the squamous epithelium of the right wall of the esophagogastric junction. Barrett's esophageal adenocarcinoma may spread below the squamous epithelium when the tumor is situated adjacent to the squamocolumnar junction, so that it is usually difficult to diagnose its presence and extent by conventional endoscopy alone. We have noted that the spread of Barrett's esophageal adenocarcinoma below the squamous epithelium is recognizable as annular vascular formations (AVF) by magnifying endoscopy with narrow-band imaging (ME-NBI), and have verified it by 3-D stereo-reconstruction using serial sections from a specimen of the same lesion. When horizontal cross-sections of the tissue were viewed from the surface, AVF emerged at a depth of approximately 100 μm from the surface and disappeared at a depth of approximately 300 μm. Therefore, it would be presumed to be difficult to visualize the characteristic structural features by ME-NBI if the carcinomatous glandular ducts were situated deeper than approximately 300 μm underneath a thick layer of squamous epithelium. Thickness of the overlying squamous epithelium may be a limiting factor for whether or not the characteristic structural features can be detected.

  10. Age and sex differences in the incidence of esophageal adenocarcinoma: results from the Surveillance, Epidemiology, and End Results (SEER) Registry (1973-2008).

    PubMed

    Mathieu, L N; Kanarek, N F; Tsai, H-L; Rudin, C M; Brock, M V

    2014-01-01

    Risk factors driving sex disparity in esophageal cancer are unclear. Recent molecular evidence suggests hormonal factors. We conducted a national descriptive epidemiological study to assess the hypothesis that estrogen exposure could explain the male predominance in observed esophageal adenocarcinoma incidence. We analyzed the esophageal cancer incidence trends by histology and sex from 1973 to 2008 in nine population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) 9 Registry Database. We used age as a proxy for estrogen exposure in females. The collective age groups annual percentage change in esophageal adenocarcinoma for females is positive (0.03%; 95% confidence interval: 0.02, 0.03%) during the study period. Interestingly, the esophageal adenocarcinoma annual percentage change in incidence rates for females during the same time period is significantly negative from ages 50-54 to ages 60-64. Even though the incidence of esophageal adenocarcinoma rises in both males and females, the male-to-female ratio across age peaks in the 50-54 years then decreases. Furthermore, the esophageal adenocarcinoma age-adjusted incidence rate in postmenopausal females age 80 and above increases with age unlike their male counterparts. Taken together, these data support the hypothesis that the endocrine milieu in pre- and perimenopausal females serves as a protective factor against esophageal adenocarcinoma, and with loss of estrogen or because of the increasing time period away from estrogen exposure, the rate of esophageal adenocarcinoma incidence increases in the older postmenopausal female. Because females comprise the largest portion of the elderly population with esophageal adenocarcinoma, these findings are significant.

  11. 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

  12. Epstein–Barr Virus in Gastro-Esophageal Adenocarcinomas – Single Center Experiences in the Context of Current Literature

    PubMed Central

    Genitsch, Vera; Novotny, Alexander; Seiler, Christian A.; Kröll, Dino; Walch, Axel; Langer, Rupert

    2015-01-01

    Epstein–Barr virus (EBV)-associated gastric carcinomas (GC) represent a distinct and well-recognized subtype of gastric cancer with a prevalence of around 10% of all GC. In contrast, EBV has not been reported to play a major role in esophageal adenocarcinomas (EAC) and adenocarcinomas of the gastro-esophageal junction (GEJ). We report our experiences on EBV in collections of gastro-esophageal adenocarcinomas from two surgical centers and discuss the current state of research in this field. Tumor samples from 465 primary resected gastro-esophageal adenocarcinomas (118 EAC, 73 GEJ, and 274 GC) were investigated. Presence of EBV was determined by EBV-encoded small RNAs (EBER) in situ hybridization. Results were correlated with pathologic parameters (UICC pTNM category, Her2 status, tumor grading) and survival. EBER positivity was observed in 14 cases. None of the EAC were positive for EBER. In contrast, we observed EBER positivity in 2/73 adenocarcinomas of the GEJ (2.7%) and 12/274 GC (4.4%). These were of intestinal type (seven cases) or unclassifiable (six cases), while only one case was of diffuse type according to the Lauren classification. No association between EBV and pT, pN, or tumor grading was found, neither was there a correlation with clinical outcome. None of the EBER positive cases were Her2 positive. In conclusion, EBV does not seem to play a role in the carcinogenesis of EAC. Moreover, adenocarcinomas of the GEJ show lower rates of EBV positivity compared to GC. Our data only partially correlate with previous reports from the literature. This highlights the need for further research on this distinct entity. Recent reports, however, have identified specific epigenetic and genetic alterations in EBV-associated GC, which might lead to a distinct treatment approach for this specific subtype of GC in the future. PMID:25859432

  13. Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.

    PubMed

    Ekiz, F; Ormeci, N; Coban, S; Karabulut, H G; Aktas, B; Tukun, A; Tuncali, T; Yüksel, O; Alkış, N

    2012-07-01

    Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma. PMID:21951971

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

    PubMed

    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

  15. 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

  16. Environmental Causes of Esophageal Cancer

    PubMed Central

    Kamangar, Farin; Chow, Wong-Ho; Abnet, Christian; Dawsey, Sanford

    2009-01-01

    Synopsis This articles reviews the environmental risk factors and predisposing conditions for the two main histological types of esophageal cancer, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EA). Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of ESCC. Results of investigations on several other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are also discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and probably absence of H. pylori in the stomach increase the risk of EA. Results of studies investigating other factors, including low intake of fresh fruits and vegetables, consumption of carbonated soft drink, use of H2 blockers, non-steroidal anti-inflammatory drugs, and drugs that relax the lower esophageal sphincter are also discussed. PMID:19327566

  17. Leukocyte telomere length in relation to the risk of Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Wennerström, E Christina M; Risques, Rosa A; Prunkard, Donna; Giffen, Carol; Corley, Douglas A; Murray, Liam J; Whiteman, David C; Wu, Anna H; Bernstein, Leslie; Ye, Weimin; Chow, Wong-Ho; Vaughan, Thomas L; Liao, Linda M

    2016-09-01

    Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease (GERD) are major risk factors associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length (LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). Telomere length was measured in leukocyte DNA samples by Q-PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population-based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study-specific odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients (OR 0.57; 95% CI: 0.35-0.93), compared to population-based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC. PMID:27384379

  18. 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

  19. Leukocyte telomere length in relation to the risk of Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    Wennerström, E Christina M; Risques, Rosa A; Prunkard, Donna; Giffen, Carol; Corley, Douglas A; Murray, Liam J; Whiteman, David C; Wu, Anna H; Bernstein, Leslie; Ye, Weimin; Chow, Wong-Ho; Vaughan, Thomas L; Liao, Linda M

    2016-09-01

    Chronic inflammation and oxidative damage caused by obesity, cigarette smoking, and chronic gastroesophageal reflux disease (GERD) are major risk factors associated with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). EAC has been increasing the past few decades, and early discovery and treatment are crucial for survival. Telomere shortening due to cell division and oxidative damage may reflect the impact of chronic inflammation and could possibly be used as predictor for disease development. We examined the prevalence of shorter leukocyte telomere length (LTL) among individuals with GERD, BE, or EAC using a pooled analysis of studies from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). Telomere length was measured in leukocyte DNA samples by Q-PCR. Participants included 1173 patients (386 with GERD, 384 with EAC, 403 with BE) and 736 population-based controls. The association of LTL (in tertiles) along the continuum of disease progression from GERD to BE to EAC was calculated using study-specific odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models adjusted for potential confounders. Shorter LTL were less prevalent among GERD patients (OR 0.57; 95% CI: 0.35-0.93), compared to population-based controls. No statistically significant increased prevalence of short/long LTL among individuals with BE or EAC was observed. In contrast to some earlier reports, our findings add to the evidence that leukocyte telomere length is not a biomarker of risk related to the etiology of EAC. The findings do not suggest a relationship between LTL and BE or EAC.

  20. 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

  1. Preference of Endoscopic Ablation Over Medical Prevention of Esophageal Adenocarcinoma by Patients with Barrett's Esophagus

    PubMed Central

    Yachimski, Patrick; Wani, Sachin; Givens, Tonya; Howard, Eric; Higginbotham, Tina; Price, Angie; Berman, Kenneth; Hosford, Lindsay; Katcher, Paul Menard; Ozanne, Elissa; Perzan, Katherine; Hur, Chin

    2014-01-01

    Background & Aims Endoscopic intervention or pharmacologic inhibition of cyclooxygenase might be used to prevent progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC). We investigated whether patients with BE prefer endoscopic therapy or chemoprevention of EAC. Methods Eighty-one subjects with nondysplastic BE were given a survey that described 2 scenarios. The survey explained that treatment A (ablation), endoscopy, reduced lifetime risk of EAC by 50%, with a 5% risk for esophageal stricture, whereas treatment B (aspirin) reduced lifetime risk of EAC by 50% and the risk of heart attack by 30%, yet increased the risk for ulcer by 75%. Subjects indicated their willingness to undergo either treatment A and/or treatment B if endoscopic surveillance was required every 3–5 years, every 10 years, or was not required. Visual aids were included to represent risk and benefit percentages. Results When surveillance was required every 3–5 years, more subjects were willing to undergo treatment A than treatment B (78% [63/81] vs 53% [43/81], P<.01). There were no differences in age, sex, education level, or history of cancer, heart disease, or ulcer between patients willing to undergo treatment A and those willing to undergo treatment B. Altering the frequency of surveillance did not affect patients’ willingness to undergo either treatment. Conclusion In a simulated scenario, patients with BE preferred endoscopic intervention over chemoprevention for EAC. Further investigation may be warranted of the shared decision making process regarding preventive strategies for patients with BE. PMID:24681073

  2. Bile acid receptor TGR5, NADPH Oxidase NOX5-S and CREB Mediate Bile Acid-Induced DNA Damage In Barrett’s Esophageal Adenocarcinoma Cells

    PubMed Central

    Li, Dan; Cao, Weibiao

    2016-01-01

    The mechanisms whereby bile acid reflux may accelerate the progression from Barrett’s esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. In this study we found that bile acid taurodeoxycholic acid (TDCA) significantly increased the tail moment (TM) and histone H2AX phosphorylation in FLO-1 EA cells, an increase which was significantly decreased by knockdown of TGR5. Overexpression of TGR5 significantly increased TDCA-induced TM increase and H2AX phosphorylation. In addition, NADPH oxidase inhibitor diphenylene iodonium significantly inhibited the TDCA-induced increase in TM and H2AX phosphorylation. TDCA-induced increase in TM and H2AX phosphorylation was significantly decreased by knockdown of NOX5-S and overexpression of NOX5-S significantly increased TDCA-induced increase in the tail moment and H2AX phosphorylation. Furthermore, TDCA significantly increased cAMP response element binding protein (CREB) phosphorylation in FLO-1 cells. Knockdown of CREB significantly decreased TDCA-induced increase in NOX5-S mRNA and the tail moment. Conversely, overexpression of CREB significantly increased TDCA-induced TM increase. We conclude that TDCA-induced DNA damage may depend on the activation of TGR5, CREB and NOX5-S. It is possible that in Barrett’s patients bile acids may activate NOX5-S and increase reactive oxygen species (ROS) production via activation of TGR5 and CREB. NOX5-S-derived ROS may cause DNA damage, thereby contributing to the progression from BE to EA. PMID:27511066

  3. Bile acid receptor TGR5, NADPH Oxidase NOX5-S and CREB Mediate Bile Acid-Induced DNA Damage In Barrett's Esophageal Adenocarcinoma Cells.

    PubMed

    Li, Dan; Cao, Weibiao

    2016-01-01

    The mechanisms whereby bile acid reflux may accelerate the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EA) are not fully understood. In this study we found that bile acid taurodeoxycholic acid (TDCA) significantly increased the tail moment (TM) and histone H2AX phosphorylation in FLO-1 EA cells, an increase which was significantly decreased by knockdown of TGR5. Overexpression of TGR5 significantly increased TDCA-induced TM increase and H2AX phosphorylation. In addition, NADPH oxidase inhibitor diphenylene iodonium significantly inhibited the TDCA-induced increase in TM and H2AX phosphorylation. TDCA-induced increase in TM and H2AX phosphorylation was significantly decreased by knockdown of NOX5-S and overexpression of NOX5-S significantly increased TDCA-induced increase in the tail moment and H2AX phosphorylation. Furthermore, TDCA significantly increased cAMP response element binding protein (CREB) phosphorylation in FLO-1 cells. Knockdown of CREB significantly decreased TDCA-induced increase in NOX5-S mRNA and the tail moment. Conversely, overexpression of CREB significantly increased TDCA-induced TM increase. We conclude that TDCA-induced DNA damage may depend on the activation of TGR5, CREB and NOX5-S. It is possible that in Barrett's patients bile acids may activate NOX5-S and increase reactive oxygen species (ROS) production via activation of TGR5 and CREB. NOX5-S-derived ROS may cause DNA damage, thereby contributing to the progression from BE to EA. PMID:27511066

  4. 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 ...

  5. Nuclear localization of Toll-like receptor 5 in Barrett's esophagus and esophageal adenocarcinoma is associated with metastatic behavior.

    PubMed

    Helminen, Olli; Huhta, Heikki; Leppänen, Joni; Kauppila, Joonas H; Takala, Heikki; Lehenkari, Petri P; Saarnio, Juha; Karttunen, Tuomo J

    2016-10-01

    Toll-like receptor 5 (TLR5) recognizes bacterial flagellin. Increased cytoplasmic and nuclear expression of some TLRs has been previously reported in dysplasia in Barrett's esophagus and various malignant lesions in association with survival and metastasis. We assessed nuclear expression of TLR5 in Barrett's esophagus and esophageal adenocarcinoma (n = 94) by immunohistochemistry and immunofluorescent staining. Nuclear expression was observed in the majority of studied lesions with high variation in the proportion of positive nuclei. Expression in lymph node metastases was significantly higher than in esophageal lesions (p < 0.05), except for intestinal metaplasia and low-grade dysplasia. Furthermore, nuclear expression of TLR5 was associated with the presence of lymph node metastases (p = 0.033). In conclusion, we report nuclear TLR5 expression in Barrett's esophagus and adenocarcinoma. Abundance of positive nuclei in association with lymph node metastases suggests that TLR5 is involved in the pathogenesis and dissemination of esophageal adenocarcinoma through as-yet-uncharacterized mechanisms.

  6. 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.

  7. Locoregional Failure Rate After Preoperative Chemoradiation of Esophageal Adenocarcinoma and the Outcomes of Salvage Strategies

    PubMed Central

    Sudo, Kazuki; Taketa, Takashi; Correa, Arlene M.; Campagna, Maria-Claudia; Wadhwa, Roopma; Blum, Mariela A.; Komaki, Ritsuko; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Skinner, Heath D.; Maru, Dipen M.; Rice, David C.; Swisher, Stephen G.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2013-01-01

    Purpose The primary purpose of surveillance of patients with esophageal adenocarcinoma (EAC) and/or esophagogastric junction adenocarcinoma after local therapy (eg, chemoradiotherapy followed by surgery or trimodality therapy [TMT]) is to implement a potentially beneficial salvage therapy to overcome possible morbidity/mortality caused by locoregional failure (LRF). However, the benefits of surveillance are not well understood. We report on LRFs and salvage strategies in a large cohort. Patients and Methods Between 2000 and 2010, 518 patients with EAC who completed TMT were analyzed for the frequency of LRF over time and salvage therapy outcomes. Standard statistical techniques were used. Results For 518 patients, the median follow-up time was 29.3 months (range, 1 to 149 months). Distant metastases (with or without LRF) occurred in 188 patients (36%), and LRF only occurred in 27 patients (5%). Eleven of 27 patients had lumen-only LRF. Most LRFs (89%) occurred within 36 months of surgery. Twelve patients had salvage chemoradiotherapy, but only five survived more than 2 years. Four patients needed salvage surgery, and three who survived more than 2 years developed distant metastases. The median overall survival of 27 patients with LRF was 17 months, and 10 patients (37%) survived more than 2 years. Thus, only 2% of all 518 patients benefited from surveillance/salvage strategies. Conclusion Our surveillance strategy, which is representative of many others currently being used, raises doubts about its effectiveness and benefits (along with concerns regarding types and times of studies and costs implications) to patients with EAC who have LRF only after TMT. Fortunately, LRFs are rare after TMT, but the salvage strategies are not highly beneficial. Our data can help develop an evidence-based surveillance strategy. PMID:24145339

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

    PubMed Central

    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; Cibulskis, Kristian; Sivachenko, Andrey; Carter, Scott L.; Saksena, Gordon; Voet, Douglas; Ramos, Alex H.; Auclair, Daniel; Thompson, Kristin; Sougnez, Carrie; Onofrio, Robert C.; Guiducci, Candace; Beroukhim, Rameen; Zhou, David; Lin, Lin; Lin, Jules; Reddy, Rishindra; Chang, Andrew; Luketich, James D.; Pennathur, Arjun; Ogino, Shuji; Golub, Todd R.; Gabriel, Stacey B.; Lander, Eric S.; Beer, David G.; Godfrey, Tony E.; Getz, Gad; Bass, Adam J.

    2013-01-01

    The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a five-year survival rate of 15%, identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole exome sequencing of 149 EAC tumors/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 to C transversions at AA dinucleotides. Statistical analysis of exome data identified significantly mutated 26 genes. Of these genes, four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include chromatin modifying factors and candidate contributors: SPG20, TLR4, ELMO1, and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 reveal increased cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis. PMID:23525077

  10. 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

  11. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

    PubMed

    Secrier, Maria; Li, Xiaodun; de Silva, Nadeera; Eldridge, Matthew D; Contino, Gianmarco; Bornschein, Jan; MacRae, Shona; Grehan, Nicola; O'Donovan, Maria; Miremadi, Ahmad; Yang, Tsun-Po; Bower, Lawrence; Chettouh, Hamza; Crawte, Jason; Galeano-Dalmau, Núria; Grabowska, Anna; Saunders, John; Underwood, Tim; Waddell, Nicola; Barbour, Andrew P; Nutzinger, Barbara; Achilleos, Achilleas; Edwards, Paul A W; Lynch, Andy G; Tavaré, Simon; Fitzgerald, Rebecca C

    2016-10-01

    Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection. PMID:27595477

  12. 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

  13. 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

  14. Genome-wide analysis of esophageal adenocarcinoma yields specific copy number aberrations that correlate with prognosis.

    PubMed

    Frankel, Adam; Armour, Nicola; Nancarrow, Derek; Krause, Lutz; Hayward, Nicholas; Lampe, Guy; Smithers, B Mark; Barbour, Andrew

    2014-04-01

    The incidence of esophageal adenocarcinoma (EAC) has been increasing rapidly for the past 3 decades in Western (Caucasian) populations. Curative treatment is based around esophagectomy, which has a major impact on quality of life. For those suitable for treatment with curative intent, 5-year survival is ∼30%. More accurate prognostic tools are therefore needed, and copy number aberrations (CNAs) may offer the ability to act as prospective biomarkers in this regard. We performed a genome-wide examination of CNAs in 54 samples of EAC using single-nucleotide polymorphism (SNP) arrays. Our aims were to describe frequent regions of CNA, to define driver CNAs, and to identify CNAs that correlated with survival. Regions of frequent amplification included oncogenes such as EGFR, MYC, KLF12, and ERBB2, while frequently deleted regions included tumor suppressor genes such as CDKN2A/B, PTPRD, FHIT, and SMAD4. The genomic identification of significant targets in cancer (GISTIC) algorithm identified 24 regions of gain and 28 regions of loss that were likely to contain driver changes. We discovered 61 genes in five regions that, when stratified by CNA type (gain or loss), correlated with a statistically significant difference in survival. Pathway analysis of the genes residing in both the GISTIC and prognostic regions showed they were significantly enriched for cancer-related networks. Finally, we discovered that copy-neutral loss of heterozygosity is a frequent mechanism of CNA in genes currently targetable by chemotherapy, potentially leading to under-reporting of cases suitable for such treatment.

  15. The role of gastroesophageal reflux and other factors during progression to esophageal adenocarcinoma

    PubMed Central

    Hazelton, William D.; Curtius, Kit; Inadomi, John M.; Vaughan, Thomas L.; Meza, Rafael; Rubenstein, Joel H.; Hur, Chin; Luebeck, E. Georg

    2015-01-01

    Background US esophageal adenocarcinoma (EAC) incidence increased over five-fold between 1975 and 2009. Symptomatic gastroesophageal reflux disease (sGERD) elevates the risk for EAC. However, a simple calculation suggests that changes in sGERD prevalence can explain at most ~16% of this trend. Importantly, a mechanistic understanding of the influence of sGERD and other factors (OF) on EAC is lacking. Methods A multiscale model was developed to estimate temporal trends for sGERD and OF, and their mechanistic role during carcinogenesis. Model calibration was to Surveillance, Epidemiology, and End Results (SEER) incidence and age-dependent sGERD data using maximum likelihood and Markov chain Monte Carlo (MCMC) methods. Results Among men, 77.8% [95% Credibility Interval (CI) = 64.9 – 85.6%] of the incidence trend is attributable to OF, 13.4% [95% CI = 11.4 – 17.3%] to sGERD, and 8.8% [95% CI = 4.2 – 13.7%] to sGERD-OF interactions. Among women, 32.6% [95% CI = 27.0 – 39.9%] of the trend is attributable to OF, 13.6% [95% CI = 12.5 – 15.9%] to sGERD, and 47.4% [95% CI = 30.7 – 64.6%] to interactions. The predicted trends were compared with historical trends for obesity, smoking, and proton pump inhibitor use. Interestingly, predicted OF cohort trends correlated most highly with median body mass index (BMI) at age 50, (r = 0.988 for men; r = 0.998 for women). Conclusions sGERD and OF mechanistically increase premalignant cell promotion, which increases EAC risk exponentially with exposure duration. Impact Surveillance should target individuals with long-duration sGERD and OF exposures. PMID:25931440

  16. Single nucleotide polymorphisms in CRTC1 and BARX1 are associated with esophageal adenocarcinoma

    PubMed Central

    van Nistelrooij, Anna M. J.; van der Korput, Hetty A. G. M.; Broer, Linda; van Marion, Ronald; van Berge Henegouwen, Mark I.; van Noesel, Carel J.; Biermann, Katharina; Spaander, Manon C. W.; Tilanus, Hugo W.; van Lanschot, J. Jan B.; Hofman, Albert; Uitterlinden, André G.; Wijnhoven, Bas P. L.; Dinjens, Winand N. M.

    2015-01-01

    Objective: Recently, single nucleotide polymorphisms (SNPs) associated with esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE) were identified; rs10419226 (CRTC1), rs11789015 (BARX1), rs2687201 (FOXP1), rs2178146 (FOXF1), rs3111601 (FOXF1), and rs9936833 (FOXF1). These findings indicate that genetic susceptibility could play a role in the initiation of EAC in BE patients. The aim of this study was to validate the association between these previously identified SNPs and the risk of EAC in an independent and large case–control study. Design: Six SNPs found to be associated with EAC and BE were genotyped by a multiplex SNaPshot analysis in 1071 EAC patients diagnosed and treated in the Netherlands. Allele frequencies were compared to a control group derived from the Rotterdam Study, a population-based prospective cohort study (n = 6206). Logistic regression analysis and meta-analysis were performed to calculate odds ratios (OR). Results: Rs10419226 (CRTC1) showed a significantly increased EAC risk for the minor allele (OR = 1.17, P = 0.001), and rs11789015 (BARX1) showed a significantly decreased risk for the minor allele (OR = 0.85, P = 0.004) in the logistic regression analysis. The meta-analysis of the original GWAS and the current study revealed an improved level of significance for rs10419226 (CRTC1) (OR = 1.18, P = 6.66 × 10–10) and rs11789015 (BARX1) (OR = 0.83, P = 1.13 × 10–8). Conclusions: This independent and large Dutch case–control study confirms the association of rs10419226 (CRTC1) and rs11789015 (BARX1) with the risk of EAC. These findings suggest a contribution of the patient genetic make-up to the development of EAC and might contribute to gain more insight in the etiology of this cancer. PMID:26085818

  17. [A case of long-term survival after resection for postoperative solitary adrenal metastasis from esophageal adenocarcinoma].

    PubMed

    Saito, Hiroshige; Shuto, Kiyohiko; Ota, Takumi; Toma, Takayuki; Ohira, Gaku; Natsume, Toshiyuki; Uesato, Masaya; Akutsu, Yasunori; Kono, Tsuguaki; Matsubara, Hisahiro

    2010-11-01

    A 71-year-old man presented with chief complains of hoarseness and dysphagia. He was diagnosed to have an advanced esophageal adenocarcinoma in the middle thoracic esophagus for which chemoradiation therapy was started. Partial response was observed and he was referred to our hospital thereafter. After detailed examination, he underwent a subtotal esophagectomy followed by two-field lymphadenectomy in May 2001. Histopathological examination revealed a complete response. Ten months later, hematological examination showed a high serum CEA level and CT scan disclosed mediastinal lymph node recurrences. He received a course of systemic chemotherapy so called FP therapy and five months later, a course of combination chemotherapy with 700 mg/m2 5-FU on days 1-5 and 70 mg/m2 nedaplatin on day 1 was administered. Because the high serum CEA level sustained afterward, FDG-PET was undertaken in March 2003. The right adrenal gland showed an intense abnormal FDG uptake and CT scan detected a low density mass in the area. Since no metastases could be identified in other sites, right adrenalectomy was performed. Pathological finding was poorly-differentiated tubular adenocarcinoma. Five years and eleven months after adrenalectomy, he died of pneumonia with no signs of recurrence. Surgical resection may contribute to improving the prognosis of solitary adrenal metastasis of esophageal cancer without the other noncurative factors.

  18. 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.

  19. 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

  20. Fourier transform infrared (FTIR) spectromicroscopic characterization of stem-like cell populations in human esophageal normal and adenocarcinoma cell lines.

    PubMed

    Zhao, R; Quaroni, L; Casson, A G

    2010-01-01

    We have tested an approach to identify putative cancer stem cells that involves measurement of the infrared absorption spectrum of individual cells in an aqueous environment, and their subsequent classification using multivariate data analysis techniques. Two primary esophageal cell lines were characterized: the immortalized normal esophageal epithelial cell line, Het-1A, and the esophageal adenocarcinoma cell line, OE33. In addition, we also evaluated spheroids, reflecting stem-like cell populations, which were derived from each parent cell line when grown in serum-free media. As differences in cell size appeared to be a strong discriminating factor, a correction needs to be performed to allow a reliable classification based on infrared absorption spectra. We demonstrated that stem-like cells derived from Het-1A could easily be discriminated on the basis of absorbance differences in the 1000-1200 cm(-1) spectral interval, whereas this was not possible for OE33. Furthermore, we found that changes due to aging of OE33 cells in culture dominated the infrared absorption spectra and somewhat limited the potential of this approach to identify stem-like cell populations using this in vitro model system.

  1. 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

  2. Magnitude of Missed Esophageal Adenocarcinoma After Barrett's Esophagus Diagnosis: A Systematic Review and Meta-analysis

    PubMed Central

    Visrodia, Kavel; Singh, Siddharth; Krishnamoorthi, Rajesh; Ahlquist, David A.; Wang, Kenneth K.; Iyer, Prasad G.; Katzka, David A.

    2016-01-01

    Background & Aims A proportion of patients with Barrett's esophagus (BE) are diagnosed with esophageal adenocarcinoma (EAC) within 1 year of an endoscopic examination that produced negative findings. These cases of missed cancers have not been well studied, despite current surveillance strategies for BE. We performed a systematic review and meta-analysis to determine the magnitude of missed EAC in cohorts of patients with BE. Methods We searched MEDLINE, EMBASE, and Web of Science from their inception to May 31, 2015 to identify cohort studies of adults with BE (baseline nondysplastic BE ± BE with low-grade dysplasia) and at least a 3-year follow-up period, providing data on missed and incident EACs (diagnosed within 1 year and diagnosed more than 1 year after the initial endoscopy in which BE was diagnosed, respectively). The main outcome measure was pooled proportion of missed and incident EACs (of all EACs detected after initial endoscopy) among BE cohorts, using a random effects model. Results In a metaanalysis of 24 studies reporting on 820 missed and incident EACs, 25.3% were classified as missed (95% confidence interval: 16.4%–36.8%) and 74.7% as incident EACs (95% CI: 63.2%–83.6%), although there was substantial heterogeneity among studies (I2 = 74%). When the analysis was restricted to nondysplastic BE cohorts (15 studies), 23.9% of EACs were classified as missed (95% confidence interval: 15.3%–35.4%; I2 = 0%). In a meta-analysis of 10 studies with follow-up periods of ≥5 years (a total of 239 EACs), 22.0% were classified as missed (95% confidence interval: 8.7%–45.5%), with substantial heterogeneity (I2 = 68%). Conclusions Among adults with nondysplastic BE (or BE with low-grade dysplasia) at their index endoscopy and at least a 3-year follow-up period, 25% of EACs are diagnosed within 1 year after the index endoscopy. Additional resources should be allocated to detect missed EAC. PMID:26619962

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

    PubMed Central

    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.

    2015-01-01

    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

  4. Endothelial-mesenchymal transition in normal human esophageal endothelial cells cocultured with esophageal adenocarcinoma cells: role of IL-1β and TGF-β2.

    PubMed

    Nie, Linghui; Lyros, Orestis; Medda, Rituparna; Jovanovic, Nebojsa; Schmidt, Jamie L; Otterson, Mary F; Johnson, Christopher P; Behmaram, Behnaz; Shaker, Reza; Rafiee, Parvaneh

    2014-11-01

    Endothelial-mesenchymal transition (EndoMT) has been recognized as a key determinant of tumor microenvironment in cancer progression and metastasis. Endothelial cells undergoing EndoMT lose their endothelial markers, acquire the mesenchymal phenotype, and become more invasive with increased migratory abilities. Early stages of esophageal adenocarcinoma (EAC) are characterized by strong microvasculature whose impact in tumor progression remains undefined. Our aim was to determine the role of EndoMT in EAC by investigating the impact of tumor cells on normal primary human esophageal microvascular endothelial cells (HEMEC). HEMEC were either cocultured with OE33 adenocarcinoma cells or treated with IL-1β and transforming growth factor-β2 (TGF-β2) for indicated periods and analyzed for EndoMT-associated changes by real-time PCR, Western blotting, immunofluorescence staining, and functional assays. Additionally, human EAC tissues were investigated for detection of EndoMT-like cells. Our results demonstrate an increased expression of mesenchymal markers [fibroblast-specific protein 1 (FSP1), collagen1α2, vimentin, α-smooth muscle actin (α-SMA), and Snail], decreased expression of endothelial markers [CD31, von Willebrand factor VIII (vWF), and VE-cadherin], and elevated migration ability in HEMEC following coculture with OE33 cells. The EndoMT-related changes were inhibited by IL-1β and TGF-β2 gene silencing in OE33 cells. Recombinant IL-1β and TGF-β2 induced EndoMT in HEMEC. Although the level of VEGF expression was elevated in EndoMT cells, the angiogenic property of these cells was diminished. In vivo, by immunostaining EndoMT-like cells were detected at the invasive front of EAC. Our findings underscore a significant role for EndoMT in EAC and provide new insights into the mechanisms and significance of EndoMT in the context of tumor progression.

  5. Can the Risk of Lymph Node Metastases Be Gauged in Endoscopically Resected Submucosal Esophageal Adenocarcinomas? A Multi-Center Study.

    PubMed

    Boys, Joshua A; Worrell, Stephanie G; Chandrasoma, Parakrama; Vallone, John G; Maru, Dipen M; Zhang, Lizhi; Blackmon, Shanda H; Dickinson, Karen J; Dunst, Christy M; Hofstetter, Wayne L; Lada, Michael J; Louie, Brian E; Molena, Daniela; Watson, Thomas J; DeMeester, Steven R

    2016-01-01

    Endoscopic resection (ER) allows for local therapy of superficial esophageal cancers. Factors reported to be associated with an increased risk of lymph node metastases in patients with adenocarcinoma are poor differentiation, lymphovascular invasion (LVI), and submucosal invasion >500 μ. The aim of this study was to determine whether depth of invasion and tumor characteristics in an ER specimen can be used to gauge the risk of lymph node metastases in patients with superficial esophageal adenocarcinoma. Patients from seven US centers that had ER of an adenocarcinoma followed by an esophagectomy were identified. The ER pathology slides were rereviewed by three experienced GI pathologists for depth of invasion, presence of LVI, and tumor differentiation. The findings from the ER specimen were correlated with the presence and number of lymph node metastases in the final esophagectomy specimen. There were 19 T1a and 23 T1b tumors. A median of 24 nodes were resected per patient. None of the T1a tumors had involved lymph nodes despite the presence of LVI in 5% and poor differentiation in 21% of patients. In contrast, 26% of T1b tumors had involved nodes. None of the four patients with submucosal invasion ≤500 μ, no LVI, and no poor differentiation had involved nodes. However, with an increasing number of risk factors, the likelihood of involved lymph nodes increased, reaching 50% when all three factors were present. Endoscopic therapy appears appropriate for intramucosal tumors and may be an option for low-risk T1b tumors. Esophagectomy is preferred for patients with submucosal invasion and one or more risk factors.

  6. Clinicopathologic characteristics and survival outcomes of patients with advanced esophageal, gastroesophageal junction, and gastric adenocarcinoma: a single-institution experience

    PubMed Central

    Dechaphunkul, A.; Mulder, K.; El-Gehani, F.; Ghosh, S.; Deschenes, J.; Spratlin, J.

    2012-01-01

    Most patients with gastric or gastroesophageal junction (gej) cancer are diagnosed with inoperable advanced or metastatic disease. In these cases, chemotherapy is the only treatment demonstrating survival benefit. The present study compares clinicopathologic characteristics and survival outcomes for patients with advanced esophageal, gej, and gastric adenocarcinoma treated with first-line chemotherapy [epirubicin–cisplatin–5-fluorouracil (ecf), epirubicin–cisplatin–capecitabine (ecx), or etoposide–leucovorin–5-fluorouracil (elf)] or best supportive care (bsc) at our institution with those for historical controls. Methods We retrospectively reviewed medical information for 401 patients with newly diagnosed advanced esophageal, gej, or gastric adenocarcinoma treated with first-line chemotherapy (ecf, ecx, or elf) or bsc from January 1, 2004, through December 31, 2010. Descriptive statistics were used to compare the data collected with data for historical control patients. Results Of the study patients, 93% were diagnosed with metastatic disease (n = 374), and 63% received bsc only (n = 251). The main reasons that patients received bsc only included poor Eastern Cooperative Oncology Group performance status (55%), patient decision (31%), and comorbidities (14%). Of the remaining patients, 98 (24%) received ecf or ecx and 52 (13%) received elf as first-line treatment. Median overall survival was significantly longer in patients treated with ecf or ecx or with elf than in those receiving bsc (12.7 months vs. 12.7 months vs. 5.5 months respectively). Chemotherapy also significantly reduced the risk of death (64% reduction with ecf or ecx, 58% with elf). Conclusions We confirmed the substantial overall survival benefit of combination chemotherapy compared with bsc, with better survival in our patient population than in historical controls. However, novel treatment options are still warranted to improve outcomes in this patient population. PMID:23300355

  7. Copy number detection in discordant monozygotic twins of Congenital Diaphragmatic Hernia (CDH) and Esophageal Atresia (EA) cohorts.

    PubMed

    Veenma, Danielle; Brosens, Erwin; de Jong, Elisabeth; van de Ven, Cees; Meeussen, Connie; Cohen-Overbeek, Titia; Boter, Marjan; Eussen, Hubertus; Douben, Hannie; Tibboel, Dick; de Klein, Annelies

    2012-03-01

    The occurrence of phenotypic differences between monozygotic (MZ) twins is commonly attributed to environmental factors, assuming that MZ twins have a complete identical genetic make-up. Yet, recently several lines of evidence showed that both genetic and epigenetic factors could have a role in phenotypic discordance after all. A high occurrence of copy number variation (CNV) differences was observed within MZ twin pairs discordant for Parkinson's disease, thereby stressing on the importance of post-zygotic mutations as disease-predisposing events. In this study, the prevalence of discrepant CNVs was analyzed in discordant MZ twins of the Esophageal Atresia (EA) and Congenital Diaphragmatic Hernia (CDH) cohort in the Netherlands. Blood-derived DNA from 11 pairs (7 EA and 4 CDH) was screened using high-resolution SNP arrays. Results showed an identical copy number profile in each twin pair. Mosaic chromosome gain or losses could not be detected either with a detection threshold of 20%. Some of the germ-line structural events demonstrated in five out of eleven twin pairs could function as a susceptible genetic background. For example, the 177-Kb loss of chromosome 10q26 in CDH pair-3 harbors the TCF7L2 gene (Tcf4 protein), which is implicated in the regulation of muscle fiber type development and maturation. In conclusion, discrepant CNVs are not a common cause of twin discordancy in these investigated congenital anomaly cohorts. PMID:22071887

  8. Esophagitis

    MedlinePlus

    ... swelling of the esophagus. The esophagus is the tube that leads from the back of the mouth to the stomach. Causes Esophagitis is often caused by stomach fluid that flows back into the esophagus. The fluid contains acid ...

  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.

  10. Nano-curcumin inhibits proliferation of esophageal adenocarcinoma cells and enhances the T cell mediated immune response.

    PubMed

    Milano, Francesca; Mari, Luigi; van de Luijtgaarden, Wendy; Parikh, Kaushal; Calpe, Silvia; Krishnadath, Kausilia K

    2013-01-01

    In Western countries the incidence of the esophageal adenocarcinoma (EAC) has risen at a more rapid rate than that of any other malignancy. Despite intensive therapies this cancer is associated with extreme high morbidity and mortality. For this reason, novel effective therapeutic strategies are urgently required. Dendritic Cell (DC)-based immunotherapy is a promising novel treatment strategy, which combined with other anti-cancer strategies has been proven to be beneficial for cancer patients. Curcumin (diferuloylmethane), is a natural polyphenol that is known for its anti-cancer effects however, in it's free form, curcumin has poor bioavailability. The aim of this study was to investigate whether using a highly absorptive form of curcumin, dispersed with colloidal nano-particles, named Theracurmin would be more effective against EAC cells and to analyze if this new compound affects DC-induced T cell response. As a result, we show efficient uptake of nano-curcumin by the EAC cell lines, OE33, and OE19. Moreover, nano-curcumin significantly decreased the proliferation of the EAC cells, while did not affect the normal esophageal cell line HET-1A. We also found that nano-curcumin significantly up-regulated the expression of the co-stimulatory molecule CD86 in DCs and significantly decreased the secretion of pro-inflammatory cytokines from in vitro activated T cells. When we combined T cells with nano-curcumin treatment in OE19 and OE33, we found that the basic levels of T cell induced cytotoxicity of 6.4 and 4.1%, increased to 15 and 13%, respectively. In conclusion, we found that nano-curcumin is effective against EAC, sensitizes EAC cells to T cell induced cytotoxicity and decreases the pro-inflammatory signals from T cells. Combining DC immunotherapy with nano-curcumin is potentially a promising approach for future treatment of EAC. PMID:23755374

  11. 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

  12. Meat and heme iron intake and esophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study.

    PubMed

    Jakszyn, Paula; Luján-Barroso, Leila; Agudo, Antonio; Bueno-de-Mesquita, H Bas; Molina, Esther; Sánchez, Ma José; Fonseca-Nunes, Ana; Siersema, Peter D; Matiello, Amalia; Tumino, Rosario; Saieva, Calogero; Pala, Valeria; Vineis, Paolo; Boutron-Ruault, Marie-Christine; Racine, Antoine; Bastide, Nadie; Travis, Ruth C; Khaw, Kay-Tee; Riboli, Elio; Murphy, Neil; Vergnaud, Anne-Claire; Trichopoulou, Antonia; Valanou, Elissavet; Oikonomidou, Edespina; Weiderpass, Elisabete; Skeie, Guri; Johansen, Dorthe; Lindkvist, Björn; Johansson, Mattias; Duarte-Salles, Talita; Freisling, Heinz; Barricarte, Aurelio; Huerta, Jose Ma; Amiano, Pilar; Tjonneland, Anne; Overvad, Kim; Kuehn, Tilman; Grote, Verena; Boeing, Heiner; Peeters, Petra H M; González, Carlos A

    2013-12-01

    Although recent studies suggest that high intakes of meat and heme iron are risk factors for several types of cancer, studies in relation to esophageal adenocarcinoma (EAC) are scarce. Previous results in the European Prospective Investigation into Cancer and Nutrition (EPIC) based on a relatively small number of cases suggested a positive association between processed meat and EAC. In this study, we investigate the association between intake of different types of meats and heme iron intake and EAC risk in a larger number of cases from EPIC. The study included 481,419 individuals and 137 incident cases of EAC that occurred during an average of 11 years of follow-up. Dietary intake of meat (unprocessed/processed red and white meat) was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat. After adjusting for relevant confounders, we observed a statistically significant positive association of EAC risk with heme iron and processed meat intake, with HR: 1.67, 95% CI: 1.05-2.68 and HR: 2.27, 95% CI:1.33-3.89, respectively, for comparison of the highest vs. lowest tertile of intake. Our results suggest a potential association between higher intakes of processed meat and heme iron and risk of EAC.

  13. 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

  14. Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction.

    PubMed

    Paeschke, Anna; Bojarski, Christian; Küpferling, Susanne; Hucklenbroich, Thomas; Siegmund, Britta; Daum, Severin

    2016-01-01

    Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS) have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ) [type I, cT3cN+cM1 (hep), CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution. PMID:27462189

  15. Unintentional Long-Term Esophageal Stenting due to a Complete Response in a Patient with Stage UICC IV Adenocarcinoma of the Gastroesophageal Junction

    PubMed Central

    Paeschke, Anna; Bojarski, Christian; Küpferling, Susanne; Hucklenbroich, Thomas; Siegmund, Britta; Daum, Severin

    2016-01-01

    Endoscopic stent implantation is a common short-treatment option in palliative settings in patients with esophageal cancer. Advanced disease is associated with low survival rates; therefore, data on the long-term outcome are limited. So far, cases of long-term remission or even cure of metastasized adenocarcinoma of the gastroesophageal junction or stomach (AGS) have only been reported from Asia. A 51-year-old male patient primarily diagnosed with metastasized adenocarcinoma of the gastroesophageal junction (GEJ) [type I, cT3cN+cM1 (hep), CEA positive, UICC stage IV] received palliative esophageal stenting with a self-expandable metal stent. As disease progressed after four cycles with epirubicin, oxaliplatin, and capecitabin, treatment was changed to 5-FU and Irinotecan. The patient did not return after 5 cycles of FOLFIRI, but presented 4 years later with mild dysphagia. Endoscopy surprisingly revealed no relevant stenosis or stent migration. Repeated histological analyses of a residual mass at the GEJ did not detect malignancy. Since the initially diagnosed hepatic metastases were no longer detectable by computed tomography, cure from esophageal cancer was assumed. Dysphagia was ascribed to esophageal motility disorder by a narrowed esophageal lumen after long-term stenting. Thus, endoscopic stent implantation is an important method in palliative treatment of dysphagia related to AGS. New systemic treatment strategies like trastuzumab in Her2neu positive cases or new VEGF-inhibitors like ramucirumab will lead to more long-time survivors with AGS. In conclusion, future endoscopic treatment strategies in AGS represent a challenge for the development of new stent techniques in either extraction or programmed complete dissolution. PMID:27462189

  16. Metastatic tumours in upper maxillary bone of esophageal adenocarcinoma. A case report.

    PubMed

    Sánchez-Jiménez, Juan; Acebal-Blanco, Faustino; Arévalo-Arévalo, Rafael E; Molina-Martínez, Manuel

    2005-01-01

    Metastases in the oral cavity are rare lesions which represent approximately 1% of all malignant neoplasms in the oral cavity. Oral metastases are located in the mandible 80-90% on average, the maxilla location being rarer. Metastases in mouth soft tissue are also rare, and within these it is on the gums where they more frequently occur. Primary tumours which metastasize to mouth are most commonly: lung, breast and kidney. Oral cavity metastases appear as a result of distant disease spreading and show wrong prognosis, with short survival. Here we present a clinical case of a patient diagnosed with esophagus adenocarcinoma which presented metastasis in upper-left maxillary bone.

  17. Esophageal Cancer.

    PubMed

    Alsop, Benjamin R; Sharma, Prateek

    2016-09-01

    Esophageal cancer carries a poor prognosis among gastrointestinal malignancies. Although esophageal squamous cell carcinoma predominates worldwide, Western nations have seen a marked rise in the incidence of esophageal adenocarcinoma that parallels the obesity epidemic. Efforts directed toward early detection have been difficult, given that dysplasia and early cancer are generally asymptomatic. However, significant advances have been made in the past 10 to 15 years that allow for endoscopic management and often cure in early stage esophageal malignancy. New diagnostic imaging technologies may provide a means by which cost-effective, early diagnosis of dysplasia allows for definitive therapy and ultimately improves the overall survival among patients. PMID:27546839

  18. Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma.

    PubMed

    Bayraktar, Ulas Darda; Bayraktar, Soley; Hosein, Peter; Chen, Emerson; Koniaris, Leonidas G; Rocha-Lima, Caio Max S; Montero, Alberto J

    2012-09-01

    Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. APE1-mediated DNA damage repair provides survival advantage for esophageal adenocarcinoma cells in response to acidic bile salts.

    PubMed

    Hong, Jun; Chen, Zheng; Peng, Dunfa; Zaika, Alexander; Revetta, Frank; Washington, M Kay; Belkhiri, Abbes; El-Rifai, Wael

    2016-03-29

    Chronic Gastroesophageal Reflux Disease (GERD) is the main risk factor for the development of Barrett's esophagus (BE) and its progression to esophageal adenocarcinoma (EAC). Accordingly, EAC cells are subjected to high levels of oxidative stress and subsequent DNA damage. In this study, we investigated the expression and role of Apurinic/apyrimidinic endonuclease 1 (APE1) protein in promoting cancer cell survival by counteracting the lethal effects of acidic bile salts (ABS)-induced DNA damage. Immunohistochemistry analysis of human tissue samples demonstrated overexpression of APE1 in more than half of EACs (70 of 130), as compared to normal esophagus and non-dysplastic BE samples (P < 0.01). To mimic in vivo conditions, we treated in vitro cell models with a cocktail of ABS. The knockdown of endogenous APE1 in EAC FLO-1 cells significantly increased oxidative DNA damage (P < 0.01) and DNA single- and double-strand breaks (P < 0.01), whereas overexpression of APE1 in EAC OE33 cells reversed these effects. Annexin V/PI staining indicated that the APE1 expression in OE33 cells protects against ABS-induced apoptosis. In contrast, knockdown of endogenous APE1 in FLO-1 cells increased apoptosis under the same conditions. Mechanistic investigations indicated that the pro-survival function of APE1 was associated with the regulation of stress response c-Jun N-terminal protein kinase (JNK) and p38 kinases. Pharmacological inhibition of APE1 base excision repair (BER) function decreased cell survival and enhanced activation of JNK and p38 kinases by ABS. Our findings suggest that constitutive overexpression of APE1 in EAC may be an adaptive pro-survival mechanism that protects against the genotoxic lethal effects of bile reflux episodes. PMID:26934647

  4. Glyco-centric lectin magnetic bead array (LeMBA) - proteomics dataset of human serum samples from healthy, Barrett׳s esophagus and esophageal adenocarcinoma individuals.

    PubMed

    Shah, Alok K; Lê Cao, Kim-Anh; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Baker, Peter R; Clauser, Karl R; Chalkley, Robert J; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M

    2016-06-01

    This data article describes serum glycoprotein biomarker discovery and qualification datasets generated using lectin magnetic bead array (LeMBA) - mass spectrometry techniques, "Serum glycoprotein biomarker discovery and qualification pipeline reveals novel diagnostic biomarker candidates for esophageal adenocarcinoma" [1]. Serum samples collected from healthy, metaplastic Barrett׳s esophagus (BE) and esophageal adenocarcinoma (EAC) individuals were profiled for glycoprotein subsets via differential lectin binding. The biomarker discovery proteomics dataset consisting of 20 individual lectin pull-downs for 29 serum samples with a spiked-in internal standard chicken ovalbumin protein has been deposited in the PRIDE partner repository of the ProteomeXchange Consortium with the data set identifier PRIDE: PXD002442. Annotated MS/MS spectra for the peptide identifications can be viewed using MS-Viewer (〈http://prospector2.ucsf.edu/prospector/cgi-bin/msform.cgi?form=msviewer〉) using search key "jn7qafftux". The qualification dataset contained 6-lectin pulldown-coupled multiple reaction monitoring-mass spectrometry (MRM-MS) data for 41 protein candidates, from 60 serum samples. This dataset is available as a supplemental files with the original publication [1].

  5. Glyco-centric lectin magnetic bead array (LeMBA) - proteomics dataset of human serum samples from healthy, Barrett׳s esophagus and esophageal adenocarcinoma individuals.

    PubMed

    Shah, Alok K; Lê Cao, Kim-Anh; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Baker, Peter R; Clauser, Karl R; Chalkley, Robert J; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M

    2016-06-01

    This data article describes serum glycoprotein biomarker discovery and qualification datasets generated using lectin magnetic bead array (LeMBA) - mass spectrometry techniques, "Serum glycoprotein biomarker discovery and qualification pipeline reveals novel diagnostic biomarker candidates for esophageal adenocarcinoma" [1]. Serum samples collected from healthy, metaplastic Barrett׳s esophagus (BE) and esophageal adenocarcinoma (EAC) individuals were profiled for glycoprotein subsets via differential lectin binding. The biomarker discovery proteomics dataset consisting of 20 individual lectin pull-downs for 29 serum samples with a spiked-in internal standard chicken ovalbumin protein has been deposited in the PRIDE partner repository of the ProteomeXchange Consortium with the data set identifier PRIDE: PXD002442. Annotated MS/MS spectra for the peptide identifications can be viewed using MS-Viewer (〈http://prospector2.ucsf.edu/prospector/cgi-bin/msform.cgi?form=msviewer〉) using search key "jn7qafftux". The qualification dataset contained 6-lectin pulldown-coupled multiple reaction monitoring-mass spectrometry (MRM-MS) data for 41 protein candidates, from 60 serum samples. This dataset is available as a supplemental files with the original publication [1]. PMID:27408916

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

    PubMed

    Li, Yu Hong; Qiu, Miao Zhen; Xu, Jian Ming; Sun, Guo Ping; Lu, Hui Shan; Liu, Yun Peng; Zhong, Mei Zuo; Zhang, He Long; Yu, Shi Ying; Li, Wei; Hu, Xiao Hua; Wang, Jie Jun; Cheng, Ying; Zhou, Jun Tian; Guo, Zeng Qing; Guan, Zhon Gzhen; Xu, Rui Hua

    2015-10-27

    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.

  7. Genetic variation in DNA-repair pathways and response to radiochemotherapy in esophageal adenocarcinoma: a retrospective cohort study of the Eastern Cooperative Oncology Group

    PubMed Central

    2011-01-01

    Background Recent data in esophageal cancer suggests the variant allele of a single-nucleotide polymorphism (SNP) in XRCC1 may be associated with resistance to radiochemotherapy. However, this SNP has not been assessed in a histologically homogeneous clinical trial cohort that has been treated with a uniform approach. In addition, whether germline DNA may serve as a surrogate for tumor genotype at this locus is unknown in this disease. Our objective was to assess this SNP in relation to the pathologic complete response (pCR) rate in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy in a multicenter clinical trial (Eastern Cooperative Oncology Group 1201). As a secondary aim, we investigated the rate of allelic imbalance between germline and tumor DNA. Methods Eighty-one eligible treatment-naïve subjects with newly diagnosed resectable esophageal adenocarcinoma received radiotherapy (45 Gy) concurrent with cisplatin-based chemotherapy, with planned subsequent surgical resection. The primary endpoint was pCR, defined as complete absence of tumor in the surgical specimen after radiochemotherapy. Using germline DNA from 60 subjects, we examined the base-excision repair SNP, XRCC1 Arg399Gln, and 4 other SNPs in nucleotide excision (XPD Lys751Gln and Asp312Asn, ERCC1 3' flank) and double-stranded break (XRCC2 5' flank) repair pathways, and correlated genotype with pCR rate. Paired tumor tissue was used to estimate the frequency of allelic imbalance at the XRCC1 SNP. Results The variant allele of the XRCC1 SNP (399Gln) was detected in 52% of subjects. Only 6% of subjects with the variant allele experienced a pCR, compared to 28% of subjects without the variant allele (odds ratio 5.37 for failing to achieve pCR, p = 0.062). Allelic imbalance at this locus was found in only 10% of informative subjects, suggesting that germline genotype may reflect tumor genotype at this locus. No significant association with pCR was noted

  8. 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

  9. Bile acid exposure up-regulates tuberous sclerosis complex 1/mammalian target of rapamycin pathway in Barrett's-associated esophageal adenocarcinoma.

    PubMed

    Yen, Chia-Jui; Izzo, Julie G; Lee, Dung-Fang; Guha, Sushovan; Wei, Yongkun; Wu, Tsung-Teh; Chen, Chun-Te; Kuo, Hsu-Ping; Hsu, Jung-Mao; Sun, Hui-Lung; Chou, Chao-Kai; Buttar, Navtej S; Wang, Kenneth K; Huang, Peng; Ajani, Jaffer; Hung, Mien-Chie

    2008-04-15

    Barrett's esophagus, a columnar metaplasia of the lower esophagus epithelium related to gastroesophageal reflux disease, is the strongest known risk factor for the development of esophageal adenocarcinoma (EAC). Understanding the signal transduction events involved in esophageal epithelium carcinogenesis may provide insights into the origins of EAC and may suggest new therapies. To elucidate the molecular pathways of bile acid-induced tumorigenesis, the newly identified inflammation-associated signaling pathway involving I kappaB kinases beta (IKK beta), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1) was confirmed to be activated in immortalized Barrett's CPC-A and CPC-C cells and esophageal cancer SEG-1 and BE3 cells. Phosphorylation of TSC1 and S6K1 was induced in response to bile acid stimulation. Treatment of these cells with the mTOR inhibitor rapamycin or the IKK beta inhibitor Bay 11-7082 suppressed bile acid-induced cell proliferation and anchorage-independent growth. We next used an orthotopic rat model to evaluate the role of bile acid in the progression of Barrett's esophagus to EAC. Of interest, we found high expression of phosphorylated IKK beta (pIKK beta) and phosphorylated S6K1 (pS6K1) in tumor tissues and the Barrett's epithelium compared with normal epithelium. Furthermore, immunostaining of clinical EAC tissue specimens revealed that pIKK beta expression was strongly correlated with pS6K1 level. Together, these results show that bile acid can deregulate TSC1/mTOR through IKK beta signaling, which may play a critical role in EAC progression. In addition, Bay 11-7082 and rapamycin may potentially be chemopreventive drugs against Barrett's esophagus-associated EAC.

  10. Congenital esophageal stenosis associated with esophageal atresia.

    PubMed

    McCann, F; Michaud, L; Aspirot, A; Levesque, D; Gottrand, F; Faure, C

    2015-04-01

    Congenital esophageal stenosis (CES) is a rare clinical condition but is frequently associated with esophageal atresia (EA). The aim of this study is to report the diagnosis, management, and outcome of CES associated with EA. Medical charts of CES-EA patients from Lille University Hospital, Sainte-Justine Hospital, and Montreal Children's Hospital were retrospectively reviewed. Seventeen patients (13 boys) were included. The incidence of CES in patients with EA was 3.6%. Fifteen patients had a type C EA, one had a type A EA, and one had an isolated tracheoesophageal fistula. Seven patients had associated additional malformations. The mean age at diagnosis was 11.6 months. All but two patients had non-specific symptoms such as regurgitations or dysphagia. One CES was diagnosed at the time of surgical repair of EA. In 12 patients, CES was suspected based on abnormal barium swallow. In the remaining four, the diagnostic was confirmed by esophagoscopy. Eleven patients were treated by dilation only (1-3 dilations/patient). Six patients underwent surgery (resection and anastomosis) because of failure of attempted dilations (1-7 dilations/patient). Esophageal perforation was encountered in three patients (18%). Three patients had histologically proven tracheobronchial remnants. CES associated with EA is frequent. A high index of suspicion for CES must remain in the presence of EA. Dilatation may be effective to treat some of them, but perforation is frequent. Surgery may be required, especially in CES secondary to ectopic tracheobronchial remnants.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Clinical role of ramucirumab alone or in combination with paclitaxel for gastric and gastro-esophageal junction adenocarcinoma.

    PubMed

    Davidson, Michael; Smyth, Elizabeth C; Cunningham, David

    2016-01-01

    Cancers of the stomach and gastro-esophageal junction represent a significant challenge in oncology. Despite some recent advances in genetic categorization and the development of novel agents, outcomes remain poor. The vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab is the first targeted therapy to improve survival in a molecularly unselected population, and represents a valuable new treatment option. This review describes the current treatment landscape for advanced disease, evaluates existing and ongoing research into ramucirumab, and discusses its current and potential future therapeutic role.

  18. Clinical role of ramucirumab alone or in combination with paclitaxel for gastric and gastro-esophageal junction adenocarcinoma

    PubMed Central

    Davidson, Michael; Smyth, Elizabeth C; Cunningham, David

    2016-01-01

    Cancers of the stomach and gastro-esophageal junction represent a significant challenge in oncology. Despite some recent advances in genetic categorization and the development of novel agents, outcomes remain poor. The vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab is the first targeted therapy to improve survival in a molecularly unselected population, and represents a valuable new treatment option. This review describes the current treatment landscape for advanced disease, evaluates existing and ongoing research into ramucirumab, and discusses its current and potential future therapeutic role. PMID:27524910

  19. Clinical role of ramucirumab alone or in combination with paclitaxel for gastric and gastro-esophageal junction adenocarcinoma.

    PubMed

    Davidson, Michael; Smyth, Elizabeth C; Cunningham, David

    2016-01-01

    Cancers of the stomach and gastro-esophageal junction represent a significant challenge in oncology. Despite some recent advances in genetic categorization and the development of novel agents, outcomes remain poor. The vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab is the first targeted therapy to improve survival in a molecularly unselected population, and represents a valuable new treatment option. This review describes the current treatment landscape for advanced disease, evaluates existing and ongoing research into ramucirumab, and discusses its current and potential future therapeutic role. PMID:27524910

  20. Molecular Marker Expression Is Highly Heterogeneous in Esophageal Adenocarcinoma and Does Not Predict a Response to Neoadjuvant Therapy.

    PubMed

    Bronson, Nathan W; Diggs, Brian S; Bakis, Gene; Gatter, Kenneth M; Sheppard, Brett C; Hunter, John G; Dolan, James P

    2015-12-01

    A reliable method to identify pathologic complete responders (pCR) or non-responders (NR) to neoadjuvant chemoradiation therapy (NAT) would dramatically improve therapy for esophageal cancer. The purpose of this study is to investigate if a distinct profile of prognostic molecular markers can predict pCR after neoadjuvant therapy. Expression of p53, Her-2/neu, Cox-2, Beta-catenin, E-cadherin, MMP-1, NFkB, and TGF-B was measured by immunohistochemistry in pre-treatment biopsy tissue and graded by an experienced pathologist. A pCR was defined as no evidence of malignancy on final pathology. Molecular profiles comparing responders to non-responders were analyzed using classification and regression tree analysis to investigate response to NAT and overall survival. Nineteen patients were pCRs and 34 were NRs. pCRs were more likely to be alive at follow-up than NRs (p < 0.01). Thirty-seven distinct profiles were identified. Expression of molecular markers was highly heterogeneous between patients and did not correlate with a response to NAT, survival (p = 0.47) or clinical stage (p = 0.39) when evaluated either as individual markers or in combination with other expression patterns. NAT dramatically impacts survival through a mechanism independent of known molecular markers of esophageal cancer, which are expressed in a highly heterogeneous fashion and do not predict response to NAT or survival. PMID:26394876

  1. Comparative evaluation of serum C-reactive protein (CRP) levels in the different histological subtypes of esophageal cancer (squamous cell carcinoma and adenocarcinoma of esophagus).

    PubMed

    Lukaszewicz-Zając, Marta; Mroczko, Barbara; Kozłowski, Mirosław; Nikliński, Jacek; Laudański, Jerzy; Siewko, Maria; Szmitkowski, Maciej

    2012-02-01

    Elevated C-reactive protein (CRP) levels have been found in patients with several malignancies. The aim of the present study was to analyze the diagnostic and prognostic values of CRP levels measurement in esophageal cancer (EC) patients in relation to its different histological subtypes (squamous cell carcinoma-ESCC and adenocarcinoma-AC of esophagus) and compared them with classic tumor markers-carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag). The diagnostic sensitivity, specificity, and the areas under receiver operating characteristic curves (AUC) for all the proteins tested were defined. Serum CRP levels were statistically higher in EC, ESCC, and AC patients compared to healthy subjects and significantly increased in EC and ESCC patients with the presence of lymph node and distant metastases. The percentage of elevated CRP results in all the analyzed subgroups (EC, ESCC, and AC) was higher than CEA and SCC-Ag, similarly as AUC for CRP in comparison to SCC-Ag. Serum CRP level was a significant predictor of EC and ESCC patients' survival in univariate analysis. In conclusion, these results indicate that CRP can be used as an adjunct in evaluating the tumor markers-CEA and SCC-Ag and may improve the clinical diagnosis and follow-up of EC patients, especially for ESCC subgroup.

  2. Phenotyping of peripheral blood mononuclear cells of patients with advanced heavily pre-treated adenocarcinoma of the stomach and gastro-esophageal junction.

    PubMed

    Kuehnle, Marie-Cristine; Attig, Sebastian; Britten, Cedrik M; Schulze-Bergkamen, Henning; Lordick, Florian; von Wichert, Goetz; Thuss-Patience, Peter; Stein, Alexander; Schuler, Martin; Bassermann, Florian; Sahin, Ugur; Türeci, Ozlem

    2014-12-01

    Immunotherapeutic approaches are emerging as promising new treatment options for patients with solid cancers. The host immune system in cancer patients is dysfunctional due to a number of reasons. The level of immunosuppression is variable at the time of diagnosis and depends on the particular cancer entity, stage, and prior anti-cancer therapies. For many cancer entities, the immune alterations of the respective patient population have not been further characterized even though a patient's immunophenotype may be prognostic for the course of the disease or predictive for clinical/biological response to immunotherapy. In this study, we used flow cytometry to determine the phenotype of peripheral blood mononuclear cells (PBMCs) from 30 patients with heavily pre-treated, advanced adenocarcinoma of the stomach and gastro-esophageal junction. The frequencies and activation status of relevant immune effector populations were determined in PBMCs and compared to those of healthy individuals. This report provides comprehensive immune phenotyping data of a patient population with a high medical need.

  3. BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition-Like Phenotype in Barrett’s Esophagus and Esophageal Adenocarcinoma through Induction of SNAIL2

    PubMed Central

    Kestens, Christine; Siersema, Peter D.; Offerhaus, G. Johan A.; van Baal, Jantine W. P. M.

    2016-01-01

    Background Bone morphogenetic protein 4 (BMP4) signaling is involved in the development of Barrett’s esophagus (BE), a precursor of esophageal adenocarcinoma (EAC). In various cancers, BMP4 has been found to induce epithelial-mesenchymal transition (EMT) but its function in the development of EAC is currently unclear. Aim To investigate the expression of BMP4 and several members of the BMP4 pathway in EAC. Additionally, to determine the effect of BMP4 signaling in a human Barrett’s esophagus (BAR-T) and adenocarcinoma (OE33) cell line. Methods Expression of BMP4, its downstream target ID2 and members of the BMP4 pathway were determined by Q-RT-PCR, immunohistochemistry and Western blot analysis using biopsy samples from EAC patients. BAR-T and OE33 cells were incubated with BMP4 or the BMP4 antagonist, Noggin, and cell viability and migration assays were performed. In addition, expression of factors associated with EMT (SNAIL2, CDH1, CDH2 and Vimentin) was evaluated by Q-RT-PCR and Western blot analysis. Results Compared to squamous epithelium (SQ), BMP4 expression was significantly upregulated in EAC and BE. In addition, the expression of ID2 was significantly upregulated in EAC and BE compared to SQ. Western blot analysis confirmed our results, showing an upregulated expression of BMP4 and ID2 in both BE and EAC. In addition, more phosphorylation of SMAD1/5/8 was observed. BMP4 incubation inhibited cell viability, but induced cell migration in both BAR-T and OE33 cells. Upon BMP4 incubation, SNAIL2 expression was significantly upregulated in BAR-T and OE33 cells while CDH1 expression was significantly downregulated. These results were confirmed by Western blot analysis. Conclusion Our results indicate active BMP4 signaling in BE and EAC and suggest that this results in an invasive phenotype by inducing an EMT-like response through upregulation of SNAIL2 and subsequent downregulation of CDH1. PMID:27191723

  4. 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

  5. Survival benefit of surgery with radiotherapy vs surgery alone to patients with T2-3N0M0 stage esophageal adenocarcinoma

    PubMed Central

    Tao, Guangzhou; Wang, Wanwei; Sun, Xinchen

    2016-01-01

    Background & Aims This study is designed to analyze survival benefit of (neo-) adjuvant radiotherapy to patients with T2-3N0M0 stage esophageal adenocarcinoma (EAC). Methods T2-3N0M0 stage EAC patients from 2004 to 2012 were searched from the Surveillance Epidemiology and End Results (SEER) data. Clinical factors including age, sex, race were summarized. Univariate, multivariate analysis, and stratified cox analysis based on different T stages were performed to explore the survival effect of (neo-)adjuvant radiotherapy to T2-3N0M0 stage EAC. Results T2-3N0M0 stage EAC patients with surgery were more likely to be white race, T3 stage. Univariate analysis showed sex, age, and T stage were the prognostic factors of survival (P<0.05). Multivariate analysis proved (neo-)adjuvant radiotherapy can prolong survival time of T2-3N0M0 stage EAC (P<0.05). Further analysis based on different T stages showed that both neoadjuvant radiotherapy (HR 0.615; 95% CI 0.475-0.797) and adjuvant radiotherapy (HR 0.597; 95% 0.387-0.921) significantly reduced the risk of death of T3N0M0 stage EAC, but neither of which significantly reduced death risk of T2N0M0 stage EAC (P>0.05). Conclusions sex, age are the independent prognostic factors of T2-3N0M0 EAC. Significant survival benefit of (neo-)adjuvant radiotherapy is only observed in patients with T3N0M0 stage EAC, but not in those with T2N0M0 stage. PMID:26870996

  6. Age-specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium.

    PubMed

    Drahos, Jennifer; Xiao, Qian; Risch, Harvey A; Freedman, Neal D; Abnet, Christian C; Anderson, Lesley A; Bernstein, Leslie; Brown, Linda; Chow, Wong-Ho; Gammon, Marilie D; Kamangar, Farin; Liao, Linda M; Murray, Liam J; Ward, Mary H; Ye, Weimin; Wu, Anna H; Vaughan, Thomas L; Whiteman, David C; Cook, Michael B

    2016-01-01

    Esophageal (EA) and esophagogastric junction (EGJA) adenocarcinoma have been steadily increasing in frequency in younger people; however, the etiology of these cancers is poorly understood. We therefore investigated associations of body mass index (BMI), cigarette smoking, alcohol consumption, gastroesophageal reflux and use of nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to age-specific risks of EA and EGJA. We pooled individual participant data from eight population-based, case-control studies within the international Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). The analysis included 1,363 EA patients, 1,472 EGJA patients and 5,728 control participants. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for age-specific (<50, 50-59, 60-69, ≥70 years) cancer outcomes, as well as interactions by age. BMI, smoking status and pack-years, recurrent gastroesophageal reflux and frequency of gastroesophageal reflux were positively associated with EA and EGJA in each age group. Early-onset EA (<50 years) had stronger associations with recurrent gastroesophageal reflux (OR = 8.06, 95% CI: 4.52, 14.37; peffect modification  = 0.01) and BMI (ORBMI ≥ 30 vs . <25  = 4.19, 95% CI: 2.23, 7.87; peffect modification  = 0.04), relative to older age groups. In contrast, inverse associations of NSAID use were strongest in the oldest age group (≥70 years), although this apparent difference was not statistically significant. Age-specific associations with EGJA showed similar, but slightly weaker patterns and no statistically significant differences by age were observed. Our study provides evidence that associations between obesity and gastroesophageal reflux are stronger among earlier onset EA cancers.

  7. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group

    PubMed Central

    Catalano, P.; Gibson, M. K.; Skaar, T. C.; Philips, S.; Montgomery, E. A.; Hafez, M. J.; Powell, M.; Liu, G.; Forastiere, A. A.; Benson, A. B.; Kleinberg, L. R.; Murphy, K. M.

    2013-01-01

    Purpose Germline genetic variations may partly explain the clinical observation that normal tissue tolerance to radiochemotherapy varies by individual. Our objective was to evaluate the association between single-nucleotide polymorphisms (SNPs) in radiation/platinum pathways and serious treatment-related toxicity in subjects with esophageal adenocarcinoma who received cisplatin-based preoperative radiochemotherapy. Methods In a multicenter clinical trial (E1201), 81 eligible treatment-naïve subjects with resectable esophageal adenocarcinoma received cisplatin-based chemotherapy concurrent with radiotherapy, with planned subsequent surgical resection. Toxicity endpoints were defined as grade ≥3 radiation-related or myelosuppressive events probably or definitely related to therapy, occurring during or up to 6 weeks following the completion of radiochemotherapy. SNPs were analyzed in 60 subjects in pathways related to nucleotide/base excision- or double stranded break repair, or platinum influx, efflux, or detoxification. Results Grade ≥3 radiation-related toxicity (mostly dysphagia) and myelosuppression occurred in 18 and 33% of subjects, respectively. The variant alleles of the XRCC2 5′ flanking SNP (detected in 28% of subjects) and of GST-Pi Ile-105-Val (detected in 65% of subjects) were each associated with higher odds of serious radiation-related toxicity compared to the major allele homozygote (47% vs. 9%, and 31% vs. 0%, respectively; P = 0.005). No SNP was associated with myelosuppression. Conclusions This novel finding in a well-characterized cohort with robust endpoint data supports further investigation of XRCC2 and GST-Pi as potential predictors of radiation toxicity. PMID:21286719

  8. Neoadjuvant therapy for gastroesophageal adenocarcinoma

    PubMed Central

    Samalin, Emmanuelle; Ychou, Marc

    2016-01-01

    Gastric and esophageal adenocarcinomas are one of the main causes of cancer-related death worldwide. While the incidence of gastric adenocarcinoma is decreasing, the incidence of gastroesophageal junction adenocarcinoma is rising rapidly in Western countries. Considering that surgical resection is currently the major curative treatment, and that the 5-year survival rate highly depends on the pTNM stage at diagnosis, gastroesophageal adenocarcinoma management is very challenging for oncologists. Several treatment strategies are being evaluated, and among them systemic chemotherapy, to decrease recurrences and improve overall survival. The MAGIC and FNCLCC-FFCD trials showed a survival benefit of perioperative chemotherapy in patients with operable gastric and lower esophageal cancer, and these results had an impact on the European clinical practice. New strategies, including induction chemotherapy followed by preoperative chemoradiotherapy, targeted therapies in combination with perioperative chemotherapy and the new cytotoxic regimens, are currently assessed to improve current standards and help developing patient-tailored therapeutic interventions. PMID:27298768

  9. Predictors of Progression to High-Grade Dysplasia or Adenocarcinoma in Barrett's Esophagus.

    PubMed

    Whitson, Matthew J; Falk, Gary W

    2015-06-01

    The prevalence of esophageal adenocarcinoma is increasing dramatically. Barrett's esophagus remains the most well-established risk factor for the development of esophageal adenocarcinoma. There are multiple clinical, endoscopic, and pathologic factors that increase the risk of neoplastic progression to high-grade dysplasia or esophageal adenocarcinoma in Barrett's esophagus. This article reviews both risk and protective factors for neoplastic progression in patients with Barrett's esophagus.

  10. Two-year follow-up period showing the natural history of a superficial esophageal adenocarcinoma arising in a long segment of Barrett's esophagus.

    PubMed

    Oguma, Junya; Ozawa, Soji; Kazuno, Akihito; Nitta, Miho; Ninomiya, Yamato; Tomita, Sakura

    2016-10-01

    A 55-year-old woman experienced gastrointestinal dysfunction caused by scleroderma. An initial endoscopy revealed an erosive lesion in a long segment of Barrett's esophagus, and a biopsy led to a diagnosis of ectopic gastric mucosa. Two years later, an irregular, elevated tumor developed at the same site. This tumor was suspected of having invaded the submucosal layer. A second biopsy led to a diagnosis of adenocarcinoma. The patient subsequently underwent a thoracoscopic esophagectomy. The resected specimen revealed an invasive tumor front that had invaded the deep layer of a duplicated muscularis mucosae. Intraepithelial neoplasia partially surrounded the tumor. This lesion was thought to have developed into an adenocarcinoma according to the orderly sequence of metaplasia, intraepithelial neoplasia and finally adenocarcinoma over a 2-year period. The present case suggests that erosive lesions in Barrett's esophagus should be strictly followed up by endoscopy, even if a biopsy does not reveal any neoplastic findings. PMID:27590624

  11. Motility, digestive and nutritional problems in Esophageal Atresia.

    PubMed

    Gottrand, Madeleine; Michaud, Laurent; Sfeir, Rony; Gottrand, Frédéric

    2016-06-01

    Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is a rare congenital malformation. Digestive and nutritional problems remain frequent in children with EA both in early infancy and at long-term follow-up. These patients are at major risk of presenting with gastroesophageal reflux and its complications, such as anastomotic strictures. Esophageal dysmotility is constant, and can have important consequences on feeding and nutritional status. Patients with EA need a systematic follow-up with a multidisciplinary team. PMID:26752295

  12. Esophageal malignancy: A growing concern

    PubMed Central

    Chai, Jianyuan; Jamal, M Mazen

    2012-01-01

    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

  13. 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

  14. Surgical advances in the fetus and neonate: esophageal atresia.

    PubMed

    Kunisaki, Shaun M; Foker, John E

    2012-06-01

    This article focuses on selected topics in the diagnosis and management of patients with esophageal atresia (EA) with or without tracheoesophageal fistula. The current status of prenatal diagnosis and recent advances in surgical techniques, including thoracoscopic repair for short-gap EA and tension-induced esophageal growth for long-gap EA, are reviewed. Although no consensus exists among pediatric surgeons regarding the role of these procedures in the treatment of EA, one can reasonably expect that, as they evolve, their application will become more widespread in this challenging patient population.

  15. Esophageal Cancer

    MedlinePlus

    ... esophagus, and chest wall Lung Cancer Esophageal Cancer Gastroesophageal Reflux Disease Barrett’s Esophagus Chest Wall Tumors Mediastinal Tumors ... Section Navigation Select Topic Lung Cancer Esophageal Cancer Gastroesophageal Reflux Disease Barrett’s Esophagus Chest Wall Tumors Mediastinal Tumors ...

  16. 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 ...

  17. Esophageal atresia associated with a rare vascular ring and esophageal duplication diverticulum: a case report and review of the literature.

    PubMed

    Escobar, Mauricio A; Welke, Karl F; Holland, Randall M; Caty, Michael G

    2012-10-01

    Esophageal atresia with tracheoesophageal fistula (EA-TEF) associated with a right aortic arch poses a dilemma to the pediatric surgeon, often necessitating an operative approach via a left thoracotomy. A right aortic arch may be associated with a vascular ring, and EA-TEF, too, has been reported in association with a vascular ring. Rarely, esophageal atresia is associated with a second esophageal anomaly, such as a so-called "esophageal lung." To our knowledge, there is no report of all three in one patient. We report the first case of a patient with associated EA-TEF, vascular ring (diverticulum of Kommerell), and esophageal lung. The literature is reviewed for these rare entities.

  18. Eosinophilic esophagitis in children with esophageal atresia.

    PubMed

    Dhaliwal, J; Tobias, V; Sugo, E; Varjavandi, V; Lemberg, D; Day, A; Bohane, T; Ledder, O; Jiwane, A; Adams, S; Henry, G; Dilley, A; Shi, E; Krishnan, U

    2014-01-01

    Eosinophilic esophagitis (EoE) has only rarely been reported in esophageal atresia (EA) patients. A retrospective case analysis of all EA patients born at our center between January 1999 and April 2012 was performed. A total of 113 of patients were identified; 10 patients were excluded as a result of inadequate data. Eighteen patients (17%) were diagnosed with EoE. The average number of eosinophilis was 30/high-power field (HPF) (19/HPF-80/HPF). The median age for diagnosis of EoE was 1 year and 6 months (8 months-8 years and 7 months). Children with EoE had a significantly greater incidence of reflux symptoms, dysphagia, tracheomalacia, and 'hypoxic spells' (P < 0.05). EoE patients also underwent significantly more surgery including fundoplication and aortopexy when compared with those without EoE (P < 0.0001). Although the incidence of gastrostomy was greater in the EoE group (33% vs. 13%), this was not statistically significant. Half of the EoE patients had a coexisting atopic condition at time of diagnosis. The commonest condition was asthma 7/18 (38%) followed by specific food allergy 6/18 (33%). EoE was treated in 11 patients with either swallowed fluticasone or budesonide slurry. All improved clinically. Histologically, five had complete resolution and six had partial improvement. Six children with EoE were treated with acid suppression alone. All improved clinically, and 5/6 had subsequent histological resolution. One child who received acid suppression and an exclusion diet also improved. Seven patients (38%) had an esophageal stricture at time of EoE diagnosis. Five were dilated at time of the initial endoscopy, prior to the diagnosis of EoE being available. Two patients had resolution of their strictures on medical treatment of their EoE alone and did not require further dilatation. EoE was seen in 17% of children with EA in this study. EoE should be considered in EA patients with persistent symptoms on standard reflux treatment, increasing

  19. Ultrastructural Changes of the Smooth Muscle in Esophageal Atresia.

    PubMed

    Al-Shraim, Mubarak M; Eid, Refaat A; Musalam, Adel Osman; Radad, Khaled; Ibrahim, Ashraf H M; Malki, Talal A

    2015-01-01

    Esophageal atresia (EA) with or without tracheo-esophageal fistula (TEF) is a relatively rare congenital anomaly. Despite the advances in the management techniques and neonatal intensive care, esophageal dysmotility remains a very common problem following EA/TEF repair. Our current study aimed to describe the most significant ultrastructural changes of the smooth muscle cells (SMCs) trying to highlight some of the underlying mechanisms of esophageal dysmotility following EA/TEF repair. Twenty-three biopsies were obtained from the tip of the lower esophageal pouch (LEP) of 23 patients during primary repair of EA/TEF. Light microscopic examination was performed with hematoxylin and eosin (HE), and Van Gieson's stains. Ultrastructural examination was done using transmission electron microscopy (TEM). Histopathological examination showed distortion of smooth muscle layer and deposition of an abundant amount of fibrous tissue in-between smooth muscles. Using TEM, SMCs exhibited loss of the cell-to-cell adhesion, mitochondrial vacuolation, formation of myelin figures, and apoptotic fragmentation. There were also plasmalemmal projections and formation of ghost bodies. Interestingly, SMCs were found extending pseudopodia-like projections around adjacent collagen fibers. Engulfed collagen fibers by SMCs underwent degradation within autophagic vacuoles. Degeneration of SMCs and deposition of abundant extracellular collagen fibers are prominent pathological changes in LEP of EA/TEF. These changes might contribute to the pathogenesis of esophageal dysmotility in patients who have survived EA/TEF. PMID:26548437

  20. 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; Magalhães, 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.

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

    PubMed Central

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

    2015-01-01

    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

  2. Eosinophilic esophagitis.

    PubMed

    Kedia, Saurabh; Baruah, Bhaskar Jyoti; Makharia, Govind; Ahuja, Vineet

    2015-01-01

    Eosinophilic esophagitis (EoE) is a clinico-pathological entity characterised by symptoms of esophageal dysfunction and eosinophilia on esophageal mucosal biopsies in the absence of other causes of esophageal eosinophilia. It is a chronic inflammatory condition of esophagus often characterized by refractory reflux symptoms in children and dysphagia in adults. It occurs as a result of Th2 inflammatory response to environmental triggers (food antigens) in genetically predisposed individuals. The diagnostic criteria include symptoms of esophageal dysfunction, esophageal eosinophilia (> 15/hpf), and a PPI trial (persistent eosinophilia after 8 weeks of PPI). Mainstay of treatment at present is topical steroids and dietary therapy. Maintenance treatment should be considered to prevent long term complications. PMID:27522734

  3. 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

  4. Esophagitis - infectious

    MedlinePlus

    ... conditions that suppress or weaken your immune system Organisms (germs) that cause esophagitis include fungi, yeast, and viruses. Common organisms include: Candida albicans Cytomegalovirus (CMV) Herpes simplex virus ( ...

  5. [Esophageal dysphagia].

    PubMed

    Thumshirn, M

    2007-04-01

    Dysphagia can be caused by a number of disorders such as benign or malignant obstruction of the esophagus, inflammatory alterations of the mucosa or primary esophageal motility disorders. Endoscopic evaluation is recommended for all patients to exclude malignancy and to establish or confirm a diagnosis. This article provides an overview of the most frequent inflammatory and functional esophageal disorders causing dysphagia. Clinical findings, diagnostic procedures and therapeutic management of primary esophageal motility disorders such as achalasia and diffuse esophageal spasm as well as of GERD and eosinophilic esophagitis are discussed. The diagnosis of achalasia is made by barium swallow with fluoroscopy and by manometry. Therapeutic options for achalasia are pneumatic dilatation of the esophagogastric junction, laparoscopic cardiomyotomy combined with fundoplication and botulinum toxin injection of the lower esophageal sphincter Diffuse esophageal spasm is manometrically characterized by normal peristalsis intermittently interrupted by simultaneous contractions. Potential medical therapies are PPIs for underlying GERD, smooth-muscle relaxants and antidepressant medications. GERD is a multifaceted disease caused by abnormal reflux of gastric contents into the esophagus leading to chronic symptoms or mucosal damage. Therapy includes lifestyle modifications, acid suppressive medications mainly by PPI and laparoscopic fundoplication in selected patients. Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus diagnosed histologically. The main symptom of eosinophilic esophagitis is dysphagia for solid food with imminent risk of food impaction. Systemic or topical corticosteroids are the therapy of choice.

  6. Difficult esophageal atresia: trick and treat.

    PubMed

    Conforti, Andrea; Morini, Francesco; Bagolan, Pietro

    2014-10-01

    Although most patients with esophageal atresia (EA) and tracheo-esophageal fistula (TEF) may benefit from "standard" management, which is deferred emergency surgery, some may present unexpected elements that change this paradigm. Birth weight, associated anomalies, and long gap can influence the therapeutic schedule of the patients with EA/TEF and can make their treatment tricky. As a consequence, detailed information on these aspects gives the power to develop a decision-making process as correct as possible. In this article, we will review the most important factors influencing the treatment of patients with EA/TEF and will share our experience on the diagnostic and therapeutic tips that may provide pivotal help in the management of such patients.

  7. [Urachal adenocarcinoma].

    PubMed

    Dakir, M; Dahami, Z; Sarf, I; Tahri, A; Elmrini, M; Benjelloun, S

    2001-09-01

    Cancer of the urachus is very unusual. The lesion is a mucosecretory adenocarcinoma. The diagnosis is usually established late, and has a serious prognosis because of a long clinical latency. We report a case of metastatic adenocarcinoma of the urachus revealed by hematuria. A review of the literature allows us to demonstrate the rarity of this tumour and to demonstrate its various clinical, histological, radiological and therapeutical aspects.

  8. PROGNOSTIC FACTORS AND SURVIVAL ANALYSIS IN ESOPHAGEAL CARCINOMA

    PubMed Central

    TUSTUMI, Francisco; KIMURA, Cintia Mayumi Sakurai; TAKEDA, Flavio Roberto; UEMA, Rodrigo Hideki; SALUM, Rubens Antônio Aissar; RIBEIRO-JUNIOR, Ulysses; CECCONELLO, Ivan

    2016-01-01

    ABSTRACT Background: Despite recent advances in diagnosis and treatment, esophageal cancer still has high mortality. Prognostic factors associated with patient and with disease itself are multiple and poorly explored. Aim: Assess prognostic variables in esophageal cancer patients. Methods: Retrospective review of all patients with esophageal cancer in an oncology referral center. They were divided according to histological diagnosis (444 squamous cell carcinoma patients and 105 adenocarcinoma), and their demographic, pathological and clinical characteristics were analyzed and compared to clinical stage and overall survival. Results: No difference was noted between squamous cell carcinoma and esophageal adenocarcinoma overall survival curves. Squamous cell carcinoma presented 22.8% survival after five years against 20.2% for adenocarcinoma. When considering only patients treated with curative intent resection, after five years squamous cell carcinoma survival rate was 56.6 and adenocarcinoma, 58%. In patients with squamous cell carcinoma, poor differentiation histology and tumor size were associated with worse oncology stage, but this was not evidenced in adenocarcinoma. Conclusion: Weight loss (kg), BMI variation (kg/m²) and percentage of weight loss are factors that predict worse stage at diagnosis in the squamous cell carcinoma. In adenocarcinoma, these findings were not statistically significant. PMID:27759773

  9. Esophageal perforation

    MedlinePlus

    ... object or caustic chemicals, such as household cleaners, disk batteries, and battery acid Trauma or injury to ... may have esophageal perforation. Prevention These injuries are hard to prevent. Alternative Names Perforation of the esophagus ...

  10. Esophageal anastomosis.

    PubMed

    Yuan, Y; Wang, K-N; Chen, L-Q

    2015-01-01

    This review gives an overview of the esophageal anastomosis. The history, various techniques and substitution organs, their advantages and disadvantages, healing mechanism, complications, and actual trend of this essential part of esophageal surgery are described. The history of the esophageal anastomosis extending from the first anastomosis in 1901 to today has undergone more than one century. In the early days, the success rate of the anastomosis was extremely low. As the technology progressed, the anastomosis got significant achievement. Various anastomotic techniques are currently being used. However, controversies exist on the choice of anastomotic method concerning the success rate, postoperative complication and quality of life. How to choose the method, no one can give the best answer. We searched the manuscripts about the esophageal anastomoses in recent years and studied the controversy questions about the anastomosis. Performing an esophageal anastomosis is a technical matter, and suture healing is independent of the patient's biologic situation. Every anastomosis technique has its own merit, but the outcomes were different if it was performed by different surgeons, and we also found that the complication rate of the anastomosis was mainly associated with the surgeons. So the surgeons should learn from their previous experience and others to avoid technical errors.

  11. Esophageal Microbiome in Eosinophilic Esophagitis

    PubMed Central

    Harris, J. Kirk; Fang, Rui; Wagner, Brandie D.; Choe, Ha Na; Kelly, Caleb J.; Schroeder, Shauna; Moore, Wendy; Stevens, Mark J.; Yeckes, Alyson; Amsden, Katie; Kagalwalla, Amir F.; Zalewski, Angelika; Hirano, Ikuo; Gonsalves, Nirmala; Henry, Lauren N.; Masterson, Joanne C.; Robertson, Charles E.; Leung, Donald Y.; Pace, Norman R.; Ackerman, Steven J.; Furuta, Glenn T.; Fillon, Sophie A.

    2015-01-01

    Objective The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. Design In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. Results Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. Conclusions Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD. PMID:26020633

  12. Esophageal Helicobacter pylori colonization aggravates esophageal injury caused by reflux

    PubMed Central

    Chu, Yun-Xiang; Wang, Wei-Hong; Dai, Yun; Teng, Gui-Gen; Wang, Shu-Jun

    2014-01-01

    AIM: To investigate esophageal Helicobacter pylori (H. pylori) colonization on esophageal injury caused by reflux and the related mechanisms. METHODS: An esophagitis model, with acid and bile reflux, was surgically produced in male rats. The rats were randomly divided into either: (1) an esophagogastroduodenal anastomosis (EGDA) group; (2) an EGDA with H. pylori infection group; (3) a pseudo-operation with H. pylori infection group; or (4) a pseudo-operation group. All rats were kept for 36 wk. Based on the location of H. pylori colonization, the EGDA rats with H. pylori infection were subdivided into those with concomitant esophageal H. pylori colonization or those with only gastric H. pylori colonization. The esophageal injuries were evaluated grossly and microscopically. The expressions of CDX2 and MUC2 were determined by real-time polymerase chain reaction (RT-PCR) and immunohistochemistry. Ki-67 antigen expression was determined by immunohistochemistry. The mRNA levels of cyclin D1, c-Myc, Bax and Bcl-2 were determined by RT-PCR. Cell apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method. RESULTS: Esophagitis, Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) developed in rats that underwent EGDA. When comparing rats with EGDA and concomitant esophageal H. pylori colonization to EGDA-only rats, the severity of injury (87.9 ± 5.2 vs 77.2 ± 8.6, macroscopically, 92.5 ± 8.0 vs 83.8 ± 5.5, microscopically, both P < 0.05) and the incidences of BE (80.0% vs 33.3%, P = 0.055) and EAC (60.0% vs 11.1%, P < 0.05) were increased. These increases were associated with upregulation of CDX2 and MUC2 mRNA (10.1 ± 5.4 vs 3.0 ± 2.9, 8.4 ± 4.6 vs 2.0 ± 3.2, respectively, Ps < 0.01) and protein (8.1 ± 2.3 vs 3.3 ± 3.1, 7.3 ± 4.0 vs 1.8 ± 2.7, respectively, all P < 0.05). The expression of Ki-67 (8.9 ± 0.7 vs 6.0 ± 1.7, P < 0.01) and the presence of apoptotic cells (8.3 ± 1.1 vs 5.3 ± 1.7, P < 0.01) were also increased

  13. 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.

  14. Eosinophilic esophagitis

    PubMed Central

    Gupte, Anand R; Draganov, Peter V

    2009-01-01

    Eosinophilic esophagitis is increasingly recognized in adults. The diagnosis is based on the presence of both typical symptoms and pathologic findings on esophageal biopsy. Patients usually present with dysphagia, food impaction and/or reflux-like symptoms, and biopsy of the esophagus shows more than 15 eosinophils per high-power field. In addition, it is essential to exclude the presence of known causes of tissue eosinophilia such as gastroesophageal reflux disease, infections, malignancy, collagen vascular diseases, hypersensitivity, and inflammatory bowel disease. There are no standardized protocols for the therapy of eosinophilic esophagitis. A variety of therapeutic approaches including acid suppression, dietary modifications, topical corticosteroids and endoscopic dilation can be used alone or in combination. PMID:19115464

  15. Pill esophagitis.

    PubMed

    Kikendall, J W

    1999-06-01

    Nine hundred seventy-nine cases of pill esophagitis due to nearly 100 different medications are reviewed. Pill-induced injuries occur when caustic medicinal pills dissolve in the esophagus rather than passing rapidly into the stomach as intended. Most patients suffer only self-limited pain, but esophageal hemorrhage, stricture, and perforation may occur, and fatal injuries have been reported. The incidence of this iatrogenic injury can be reduced but not eliminated by emphasizing the importance of taking pills while upright and with plenty of fluids. PMID:10372925

  16. 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

  17. High Mobility Group A proteins in esophageal carcinomas.

    PubMed

    Palumbo Júnior, Antonio; Da Costa, Nathalia Meireles; Esposito, Francesco; Fusco, Alfredo; Pinto, Luis Felipe Ribeiro

    2016-09-16

    We have recently shown that HMGA2 is overexpressed in esophageal squamous cell carcinoma (ESCC) and its detection allows to discriminate between cancer and normal surrounding tissue proposing HMGA2 as a novel diagnostic marker. Interestingly, esophageal adenocarcinoma shows an opposite behavior with the overexpression of HMGA1 but not HMGA2. Moreover, we show that the suppression of HMGA2 in 2 ESCC cell lines reduces the malignant phenotype. Then, this paper highlights a differential induction of the HMGA proteins, depending on the cancer histological type, and reinforces the perspective of an innovative esophageal cancer therapy based on the suppression of the HMGA protein function and/or expression.

  18. 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

  19. Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study

    PubMed Central

    Xiao, Q; Freedman, N D; Ren, J; Hollenbeck, A R; Abnet, C C; Park, Y

    2014-01-01

    Background: Nutrients in the one-carbon metabolism pathway may be involved in carcinogenesis. Few cohort studies have investigated the intakes of folate and related nutrients in relation to gastric and esophageal cancer. Methods: We prospectively examined the association between self-reported intakes of folate, methionine, vitamin B6, and vitamin B12 and gastric and esophageal cancer in 492 293 men and women. Results: We observed an elevated risk of esophageal squamous cell carcinoma with low intake of folate (relative risk (95% confidence interval): Q1 vs Q3, 1.91 (1.17, 3.10)), but no association with high intake. Folate intake was not associated with esophageal adenocarcinoma, gastric cardia adenocarcinoma, or non-cardia gastric adenocarcinoma. The intakes of methionine, vitamin B6, and vitamin B12 were not associated with esophageal and gastric cancer. Conclusion: Low intake of folate was associated with increased risk of esophageal squamous cell carcinoma. PMID:24481406

  20. Gastroesophageal reflux leads to esophageal cancer in a surgical model with mice

    PubMed Central

    2009-01-01

    Background Esophago-gastroduodenal anastomosis with rats mimics the development of human Barrett's esophagus and esophageal adenocarcinoma by introducing mixed reflux of gastric and duodenal contents into the esophagus. However, use of this rat model for mechanistic and chemopreventive studies is limited due to lack of genetically modified rat strains. Therefore, a mouse model of esophageal adenocarcinoma is needed. Methods We performed reflux surgery on wild-type, p53A135V transgenic, and INK4a/Arf+/- mice of A/J strain. Some mice were also treated with omeprazole (1,400 ppm in diet), iron (50 mg/kg/m, i.p.), or gastrectomy plus iron. Mouse esophagi were harvested at 20, 40 or 80 weeks after surgery for histopathological analysis. Results At week 20, we observed metaplasia in wild-type mice (5%, 1/20) and p53A135V mice (5.3%, 1/19). At week 40, metaplasia was found in wild-type mice (16.2%, 6/37), p53A135V mice (4.8%, 2/42), and wild-type mice also receiving gastrectomy and iron (6.7%, 1/15). Esophageal squamous cell carcinoma developed in INK4a/Arf+/- mice (7.1%, 1/14), and wild-type mice receiving gastrectomy and iron (21.4%, 3/14). Among 13 wild-type mice which were given iron from week 40 to 80, twelve (92.3%) developed squamous cell carcinoma at week 80. None of these mice developed esophageal adenocarcinoma. Conclusion Surgically induced gastroesophageal reflux produced esophageal squamous cell carcinoma, but not esophageal adenocarcinoma, in mice. Dominant negative p53 mutation, heterozygous loss of INK4a/Arf, antacid treatment, iron supplementation, or gastrectomy failed to promote esophageal adenocarcinoma in these mice. Further studies are needed in order to develop a mouse model of esophageal adenocarcinoma. PMID:19627616

  1. Long Upper Pouch in Esophageal Atresia: A Rare Variant.

    PubMed

    Yhoshu, Enono; Mahajan, Jai Kumar; Dash, Vedarth

    2016-01-01

    The earliest clinical sign of esophageal atresia (EA) is excessive salivation and the diagnosis is made by failure to pass an infant feeding tube (IFT) into the stomach. The diagnostic errors may occur due to presence of an unusually long upper pouch, when the IFT seems to pass into the stomach. We describe one such case and review the relevant literature. PMID:26793598

  2. Differences and similarities of adenocarcinomas of the esophagus and esophagogastric junction.

    PubMed

    Marsman, W A; Tytgat, G N J; ten Kate, F J W; van Lanschot, J J B

    2005-12-01

    During the last few decades there has been an alarming rise in the incidence of tumors originating at the esophagogastric junction (EGJ) [1]. The reason for this is unknown. Tumors of the EGJ can be categorized in two types of cancer divided according to their anatomical origin: distal esophageal adenocarcinoma and adenocarcinoma of the gastric cardia. However, due to their location, in the transitional zone of the esophagus and stomach, there is constant debate about the proper classification, staging, and management of these tumors. The etiology of distal esophageal adenocarcinoma is clearly related to gastroesophageal reflux disease (GERD) and the development of a Barrett's esophagus [2]. The etiology of adenocarcinoma of the gastric cardia is less well understood. In the present paper, we will discuss the clinical characteristics and clinical management of esophagogastric tumors. Special attention will be given to differences and similarities of adenocarcinomas of the gastric cardia and distal esophagus.

  3. Esophageal pH monitoring

    MedlinePlus

    pH monitoring - esophageal; Esophageal acidity test ... esophagitis You may need to have the following tests if your doctor suspects esophagitis : Barium swallow Esophagogastroduodenoscopy (also called upper GI endoscopy)

  4. Esophageal dilation in eosinophilic esophagitis.

    PubMed

    Richter, Joel E

    2015-10-01

    Tissue remodeling with scaring is common in adult EoE patients with long standing disease. This is the major factor contributing to their complaints of solid food dysphagia and recurrent food impactions. The best tests to define the degree of remodeling are barium esophagram, high resolution manometry and endoscopy. Many physicians are fearful to dilate EoE patients because of concerns about mucosal tears and perforations. However, multiple recent case series attest to the safety of esophageal dilation and its efficacy with many patients having symptom relief for an average of two years. This chapter will review the sordid history of esophageal dilation in EoE patients and outline how to perform this procedure safely. The key is graduated dilation over one to several sessions to a diameter of 15-18 mm. Postprocedural pain is to be expected and mucosal tears are a sign of successful dilation, not complications. In some healthy adults, occasional dilation may be preferred to regular use of medications or restricted diets. This approach is now supported by recent EoE consensus statements and societal guidelines.

  5. Thoracoscopic Esophageal Atresia with Tracheoesophageal Fistula Repair: The First Iranian Group Report, Passing the Learning Curve

    PubMed Central

    Hiradfar, Mehran; Gharavifard, Mohammad; Shojaeian, Reza; Joodi, Marjan; Nazarzadeh, Reza; Sabzevari, Alireza; Yal, Nazila; Eslami, Reza; Mohammadipour, Ahmad; Azadmand, Ali

    2016-01-01

    Background: Thoracoscopic treatment of esophageal atresia and tracheoesophageal fistula (EA+TEF) is accepted as a superior technique at least in cosmetic point of view but it is considered as an advance endoscopic procedure that needs a learning curve to be performed perfectly. This is the first report of Iranian group pediatric surgeons in thoracoscopic approach to EA. Methods and Materials: Since 2010, twenty four cases with EA+TEF underwent thoracoscopic approach in Sarvar Children Hospital (Mashhad -Iran). During the first 6 months, thoracoscopic approach to 6 cases of EA+TEF was converted to open procedure because of technical and instrumental problems. The first case of successful thoracoscopic EA repair was accomplished in 2010 and since then, 10 cases of EA+ TEF among 18 patients were treated successfully with thoracoscopic approach Results: Overall conversion rate was 58.3% but conversion rate after the primary learning curve period, was 35.7%. The main conversion causes include difficulties in esophageal anastomosis, limited exposure and deteriorating the patient's condition. Anastomotic leak and stenosis were observed in 20% and 40% respectively. Overall mortality rate was 4.2%. Conclusion: Thoracoscopic repair of esophageal atresia seems feasible and safe with considerable superiorities to the conventional method although acceptable results needs a prolonged learning curve and advanced endoscopic surgical skill. Clear judgment about the best surgical intervention for EA according to all cosmetic and functional outcomes needs further studies. PMID:27471677

  6. Desloratadine Induced Pill Esophagitis

    PubMed Central

    Alkim, Huseyin; Iscan, Mustafa

    2012-01-01

    Pill induced esophagitis is a rare complication mostly seen in patients using tetracycline and its derivatives or non-steroidal anti-inflammatory drugs. Here we present a 37 years old female patient experiencing pill esophagitis after taking desloratadine without liquid immediately before going to bed. This was the first pill esophagitis case related with desloratadine reported in the literature. Pill esophagitis is a preventable complication that consists of giving simple advice of how and when to take medication.

  7. 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.

  8. Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine.

    PubMed

    Ahrens, Theresa D; Timme, Sylvia; Hoeppner, Jens; Ostendorp, Jenny; Hembach, Sina; Follo, Marie; Hopt, Ulrich T; Werner, Martin; Busch, Hauke; Boerries, Melanie; Lassmann, Silke

    2015-01-01

    Esophageal cancers are highly aggressive tumors with poor prognosis despite some recent advances in surgical and radiochemotherapy treatment options. This study addressed the feasibility of drugs targeting epigenetic modifiers in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells. We tested inhibition of histone deacetylases (HDACs) by SAHA, MS-275, and FK228, inhibition of DNA methyltransferases by Azacytidine (AZA) and Decitabine (DAC), and the effect of combination treatment using both types of drugs. The drug targets, HDAC1/2/3 and DNMT1, were expressed in normal esophageal epithelium and tumor cells of ESCC or EAC tissue specimens, as well as in non-neoplastic esophageal epithelial (Het-1A), ESCC (OE21, Kyse-270, Kyse-410), and EAC (OE33, SK-GT-4) cell lines. In vitro, HDAC activity, histone acetylation, and p21 expression were similarly affected in non-neoplastic, ESCC, and EAC cell lines post inhibitor treatment. Combined MS-275/AZA treatment, however, selectively targeted esophageal cancer cell lines by inducing DNA damage, cell viability loss, and apoptosis, and by decreasing cell migration. Non-neoplastic Het-1A cells were protected against HDACi (MS-275)/AZA treatment. RNA transcriptome analyses post MS-275 and/or AZA treatment identified novel regulated candidate genes (up: BCL6, Hes2; down: FAIM, MLKL), which were specifically associated with the treatment responses of esophageal cancer cells. In summary, combined HDACi/AZA treatment is efficient and selective for the targeting of esophageal cancer cells, despite similar target expression of normal and esophageal cancer epithelium, in vitro and in human esophageal carcinomas. The precise mechanisms of action of treatment responses involve novel candidate genes regulated by HDACi/AZA in esophageal cancer cells. Together, targeting of epigenetic modifiers in esophageal cancers may represent a potential future therapeutic approach.

  9. Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine

    PubMed Central

    Ahrens, Theresa D; Timme, Sylvia; Hoeppner, Jens; Ostendorp, Jenny; Hembach, Sina; Follo, Marie; Hopt, Ulrich T; Werner, Martin; Busch, Hauke; Boerries, Melanie; Lassmann, Silke

    2015-01-01

    Esophageal cancers are highly aggressive tumors with poor prognosis despite some recent advances in surgical and radiochemotherapy treatment options. This study addressed the feasibility of drugs targeting epigenetic modifiers in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) cells. We tested inhibition of histone deacetylases (HDACs) by SAHA, MS-275, and FK228, inhibition of DNA methyltransferases by Azacytidine (AZA) and Decitabine (DAC), and the effect of combination treatment using both types of drugs. The drug targets, HDAC1/2/3 and DNMT1, were expressed in normal esophageal epithelium and tumor cells of ESCC or EAC tissue specimens, as well as in non-neoplastic esophageal epithelial (Het-1A), ESCC (OE21, Kyse-270, Kyse-410), and EAC (OE33, SK-GT-4) cell lines. In vitro, HDAC activity, histone acetylation, and p21 expression were similarly affected in non-neoplastic, ESCC, and EAC cell lines post inhibitor treatment. Combined MS-275/AZA treatment, however, selectively targeted esophageal cancer cell lines by inducing DNA damage, cell viability loss, and apoptosis, and by decreasing cell migration. Non-neoplastic Het-1A cells were protected against HDACi (MS-275)/AZA treatment. RNA transcriptome analyses post MS-275 and/or AZA treatment identified novel regulated candidate genes (up: BCL6, Hes2; down: FAIM, MLKL), which were specifically associated with the treatment responses of esophageal cancer cells. In summary, combined HDACi/AZA treatment is efficient and selective for the targeting of esophageal cancer cells, despite similar target expression of normal and esophageal cancer epithelium, in vitro and in human esophageal carcinomas. The precise mechanisms of action of treatment responses involve novel candidate genes regulated by HDACi/AZA in esophageal cancer cells. Together, targeting of epigenetic modifiers in esophageal cancers may represent a potential future therapeutic approach. PMID:25923331

  10. Barrett's esophageal cancer in which magnifying narrow-band imaging was useful for diagnosing extension under the squamous epithelium.

    PubMed

    Koike, Tomoyuki; Endo, Hiroyuki; Nakagawa, Kenichiro; Iijima, Katsunori; Shimosegawa, Tooru

    2013-05-01

    A 36-year-old man complained of heartburn. Gastrointestinal endoscopies showed a reddish and slightly depressed lesion in the right-anterior wall of the esophagogastric junction. With white light imaging, the area of the adenocarcinoma under the squamous epithelium was difficult to detect, but a slightly flat, elevated lesion appeared in the area of adenocarcinoma under the squamous epithelium. With narrow-band imaging (NBI) in the area of the Barrett's esophageal cancer under the squamous epithelium, a slight, brownish change could be observed. In addition, with the magnifying technique, irregular mesh-like vessels were observed, suggesting the presence of differentiated adenocarcinoma under the squamous epithelium. The lesion was resected en bloc by endoscopic submucosal dissection, and Barrett's esophageal cancer under the squamous epithelium was histologically confirmed. In this case, NBI with magnifying endoscopy was very useful to diagnose the extension of Barrett's esophageal cancer under the squamous epithelium.

  11. Etiology and Prevention of Esophageal Cancer

    PubMed Central

    Yang, Chung S.; Chen, Xiaoxin; Tu, Shuiping

    2016-01-01

    Background Esophageal cancer (EC) occurs commonly, especially in Asia, and is the sixth leading cause of cancer deaths worldwide. Recently, great progress has been made in research on the etiology and prevention of EC. Summary The major risk factors for esophageal squamous cell carcinoma (ESCC) are tobacco smoking and alcohol drinking, which act synergistically. Dietary parameters, including dietary carcinogens and insufficiency of micronutrients, could also be important risk factors in certain areas. A common etiological factor for both EC and some other cancers are low levels of intake of fruits and vegetables. With improvements in diet and drinking water in developing countries, the incidence of ESCC decreased. However, in economically well-developed countries, the incidence of esophageal adenocarcinoma (EAC) has markedly increased in the past 40 years. The major etiological factor for EAC is gastroesophageal reflux, which is also an etiological factor for gastric cardia adenocarcinoma (GCA). In certain areas of China, the occurrence of GCA is closely related to ESCC. Susceptibility genes for EC are starting to be discovered, and this may help to identify high-risk groups that have more need for preventive measures. Mitigation of the risk factors, early detection and treatment of precancerous lesions are effective approaches for prevention. Smoking cessation, avoidance of excessive alcohol, meat and caloric consumption, increasing physical activity and frequent consumption of vegetables and fruits are prudent lifestyle modifications for the prevention of EC as well as other diseases. Key Message The etiology of EC includes tobacco smoking, alcohol drinking, low levels of intake of fruits and vegetables as well as gastroesophageal reflux and susceptibility genes. Practical Implications A healthy lifestyle including smoking cessation, increasing physical activity, consumption of vegetables as well as reduction of alcohol intake and caloric consumption are major

  12. CDX2 hox gene product in a rat model of esophageal cancer

    PubMed Central

    2009-01-01

    Background Barrett's mucosa is the precursor of esophageal adenocarcinoma. The molecular mechanisms behind Barrett's carcinogenesis are largely unknown. Experimental models of longstanding esophageal reflux of duodenal-gastric contents may provide important information on the biological sequence of the Barrett's oncogenesis. Methods The expression of CDX2 hox-gene product was assessed in a rat model of Barrett's carcinogenesis. Seventy-four rats underwent esophago-jejunostomy with gastric preservation. Excluding perisurgical deaths, the animals were sacrificed at various times after the surgical treatment (Group A: <10 weeks; Group B: 10–30 weeks; Group C: >30 weeks). Results No Cdx2 expression was detected in either squamous epithelia of the proximal esophagus or squamous cell carcinomas. De novo Cdx2 expression was consistently documented in the proliferative zone of the squamous epithelium close to reflux ulcers (Group A: 68%; Group B: 64%; Group C: 80%), multilayered epithelium and intestinal metaplasia (Group A: 9%; Group B: 41%; Group C: 60%), and esophageal adenocarcinomas (Group B: 36%; Group C: 35%). A trend for increasing overall Cdx2 expression was documented during the course of the experiment (p = 0.001). Conclusion De novo expression of Cdx2 is an early event in the spectrum of the lesions induced by experimental gastro-esophageal reflux and should be considered as a key step in the morphogenesis of esophageal adenocarcinoma. PMID:19664209

  13. Persistent bronchography in a newborn with esophageal atresia.

    PubMed

    De Bernardo, Giuseppe; Sordino, Desiree; Giordano, Maurizio; Doglioni, Nicoletta; Trevisanuto, Daniele

    2016-06-01

    Esophageal atresia (EA) with tracheoesophageal fistula occurs in about 1:2,500 births. We report a case of persistent bronchography in a newborn with EA and distal tracheoesophageal fistula. A large amount of barium sulfate was injected for mistake by a tube directly in the right bronchus to evaluate the patency of the esophagus. The infant showed signs of respiratory distress; he was intubated and transported at children's Hospital Santobono Pausilipon. Here, it was performed a chest X-ray that confirmed the opacification of the right bronchial tree, and it was suspected an EA type 3b. The literature recommends that: evaluation of the patency of the esophagus, with an iodinate contrast medium, should be done in a pediatric specialized center for high risk of lung aspiration. PMID:27257464

  14. Epigenetic aberrations and targeted epigenetic therapy of esophageal cancer.

    PubMed

    Zhao, Ronghua; Casson, Alan G

    2008-09-01

    Squamous cell carcinoma of the esophagus is one of the ten most frequent malignancies worldwide, characterized by a striking geographic variation in incidence. In North America and Europe, there has recently been a marked change in the epidemiology of this disease, where incidence rates for primary esophageal adenocarcinoma have increased in excess of any other human solid tumor. Although the reasons for this are largely unknown, several molecular genetic alterations have been associated with esophageal tumor progression. In recent years, epigenetic aberrations have been increasingly recognized as an important alternative mechanism of carcinogenesis and it is anticipated that substantial progress in the treatment of esophageal malignancy will likely only be made with a clearer understanding of esophageal tumor biology. Whereas genetic mutations, deletions, or allelic losses are fixed and irreversible, epigenetic abnormalities can potentially be corrected without interfering with the fundamental sequence of the target gene. Our current understanding of epigenetics in esophageal cancer, and the potential for targeted epigenetic therapy, will be the subject of this review.

  15. Epidemiology of esophageal cancer in Japan and China.

    PubMed

    Lin, Yingsong; Totsuka, Yukari; He, Yutong; Kikuchi, Shogo; Qiao, Youlin; Ueda, Junko; Wei, Wenqiang; Inoue, Manami; Tanaka, Hideo

    2013-01-01

    In preparation for a collaborative multidisciplinary study of the pathogenesis of esophageal cancer, the authors reviewed the published literature to identify similarities and differences between Japan and China in esophageal cancer epidemiology. Esophageal squamous cell carcinoma (ESCC) is the predominant histologic type, while the incidence of esophageal adenocarcinoma remains extremely low in both countries. Numerous epidemiologic studies in both countries show that alcohol consumption and cigarette smoking are contributing risk factors for ESCC. There are differences, however, in many aspects of esophageal cancer between Japan and China, including cancer burden, patterns of incidence and mortality, sex ratio of mortality, risk factor profiles, and genetic variants. Overall incidence and mortality rates are higher in China than in Japan, and variation in mortality and incidence patterns is greater in China than in Japan. During the study period (1987-2000), the decline in age-adjusted mortality rates was more apparent in China than in Japan. Risk factor profiles differed between high- and low-incidence areas within China, but not in Japan. The association of smoking and drinking with ESCC risk appears to be weaker in China than in Japan. Genome-wide association studies in China showed that variants in several chromosome regions conferred increased risk, but only genetic variants in alcohol-metabolizing genes were significantly associated with ESCC risk in Japan. A well-designed multidisciplinary epidemiologic study is needed to examine the role of diet and eating habits in ESCC risk.

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

    PubMed Central

    Belkhiri, Abbes; El-Rifai, Wael

    2015-01-01

    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

  17. Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment.

    PubMed

    Dodbiba, Lorin; Teichman, Jennifer; Fleet, Andrew; Thai, Henry; Sun, Bin; Panchal, Devang; Patel, Devalben; Tse, Alvina; Chen, Zhuo; Faluyi, Olusola O; Renouf, Daniel J; Girgis, Hala; Bandarchi, Bizhan; Schwock, Joerg; Xu, Wei; Bristow, Robert G; Tsao, Ming-Sound; Darling, Gail E; Ailles, Laurie E; El-Zimaity, Hala; Liu, Geoffrey

    2013-04-01

    There are very few xenograft models available for the study of esophageal (E) and gastro-esophageal junction (GEJ) cancer. Using a NOD/SCID model, we implanted 90 primary E and GEJ tumors resected from patients and six endoscopic biopsy specimens. Of 69 resected tumors with histologically confirmed viable adenocarcinoma or squamous cell carcinoma, 22 (32%) was engrafted. One of 11 tumors, considered to have had a complete pathological response to neo-adjuvant chemo-radiation, also engrafted. Of the 23 patients whose tumors were engrafted, 65% were male; 30% were early stage while 70% were late stage; 22% received neo-adjuvant chemo-radiation; 61% were GEJ cancers. Engraftment occurred in 18/54 (33%) adenocarcinomas and 5/16 (31%) squamous cell carcinomas. Small endoscopic biopsy tissue had a 50% (3/6) engraftment rate. Of the factors analyzed, pretreatment with chemo-radiation and well/moderate differentiation showed significantly lower correlation with engraftment (P<0.05). In the subset of patients who did not receive neo-adjuvant chemo-radiation, 18/41 (44%) engrafted compared with those with pretreatment where 5/29 (17%, P=0.02) engrafted. Primary xenograft lines may be continued through 4-12 passages. Xenografts maintained similar histology and morphological characteristics with only minor variations even after multiple passaging in most instances.

  18. [Minimal Change Esophagitis].

    PubMed

    Ryu, Han Seung; Choi, Suck Chei

    2016-01-25

    Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms and long-term complications. GERD can be divided into erosive reflux disease and non-erosive reflux disease based on endoscopic findings defined by the presence of mucosal break. The Los Angeles classification excludes minimal changes as an evidence of reflux esophagitis because of poor interobserver agreement. In the Asian literature, minimal changes are considered as one of the endoscopic findings of reflux esophagitis, but the clinical significance is still controversial. Minimal change esophagitis is recognized quite frequently among patients with GERD and many endoscopists recognize such findings in their clinical practice. This review is intended to clarify the definition of minimal change esophagitis and their histology, interobserver agreement, and symptom association with GERD.

  19. Imaging of esophageal cancer

    PubMed Central

    Iyer, R; DuBrow, R

    2004-01-01

    Esophageal cancer is a relatively uncommon gastrointestinal malignancy but carries a poor prognosis unless it is of early stage and can be surgically resected for cure. Resectability is determined by the stage of disease at diagnosis and therefore accurate staging is of importance in patients diagnosed with esophageal cancer. Imaging studies that play a role in the evaluation of esophageal cancer include barium studies, computed tomography, endoscopic ultrasound and positron emission tomography. Imaging provides important information regarding the local extent and any distant spread of disease, which in turn helps in determining optimal management for these patients. This review discusses the imaging findings that may be encountered with various imaging modalities in the diagnosis, staging and follow-up of esophageal cancer. PMID:18250021

  20. Index-Based Dietary Patterns and Risk of Esophageal and Gastric Cancer in a Large Cohort Study

    PubMed Central

    Li, Wen-Qing; Park, Yikyung; Wu, Jennifer W.; Ren, Jian-Song; Goldstein, Alisa M.; Taylor, Philip R.; Hollenbeck, Albert R.; Freedman, Neal D.; Abnet, Christian C.

    2013-01-01

    Background & Aims Diet could affect risk for esophageal and gastric cancers, but associations have been inconsistent. The diet is complex, so studies of dietary patterns, rather than studies of individual foods, might be more likely to identify cancer risk factors. There is limited research on index-based dietary patterns and esophageal and gastric cancers. We prospectively evaluated associations between the Healthy Eating Index-2005 (HEI-2005) and alternate Mediterranean Diet (aMED) scores and risk of esophageal and gastric cancers. Methods We analyzed data from 494,968 participants in the National Institutes of Health (NIH)-AARP Diet and Health study, in which AARP members (51–70 y old) completed a self-administered baseline food frequency questionnaire between 1995 and 1996. Their answers were used to estimate scores for each index. Results During the follow-up period (1995–2006), participants developed 215 esophageal squamous cell carcinomas (ESCCs), 633 esophageal adenocarcinomas (EACs), 453 gastric cardia adenocarcinomas, and 501 gastric non-cardia adenocarcinomas. Higher scores from the HEI-2005 were associated with a reduced risk of ESCC (comparing the highest quintile with the lowest: hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.31–0.86; Ptrend=.001) and EAC (HR, 0.75; 95% CI, 0.57–0.98; Ptrend=.01). We observed an inverse association between ESCC, but not EAC, and higher aMED score (meaning a higher-quality diet). HEI-2005 and aMED scores were not significantly associated with gastric cardia or noncardia adenocarcinomas. Conclusions Using data collected from 1995 through 2006 from the NIH-AARP Diet and Health Study, HEI-2005 and aMED scores were inversely associated with risk for esophageal cancers—particularly ESCC. Adherence to dietary recommendations might help prevent esophageal cancers. PMID:23591281

  1. [Eosinophilic esophagitis: update 2012].

    PubMed

    Jo, Yunju

    2012-07-01

    Eosinophilic esophagitis (EoE) with adults, as a new disease emerging during the last decade, is a clinicopathologic disorder of the esophagus characterized by a dense esophageal eosinophilic infiltration and typical esophageal symptoms. As numerous studies about EoE had been reported during last several years, updated consensus of EoE was reported in July 2011. The conceptual definition of EoE is coming. EoE is defined as a chronic, immune/antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominat inflammation. Other important addition is genotyping feature that implicates thymic stromal lymphopoietin genes or filagrrin as EoE susceptibility genes. The majority of patients has the concurrent allergic disease, especially food or aeroallergen sensitization. Main therapeutic options include topical steroids and dietary modification. Recent issues of EoE include a new concept for proton pump inhibitor-responsive esophageal eosinophilia that it should be excluded to diagnose EoE.

  2. Hedgehog signaling regulates FOXA2 in esophageal embryogenesis and Barrett’s metaplasia

    PubMed Central

    Wang, David H.; Tiwari, Anjana; Kim, Monica E.; Clemons, Nicholas J.; Regmi, Nanda L.; Hodges, William A.; Berman, David M.; Montgomery, Elizabeth A.; Watkins, D. Neil; Zhang, Xi; Zhang, Qiuyang; Jie, Chunfa; Spechler, Stuart J.; Souza, Rhonda F.

    2014-01-01

    Metaplasia can result when injury reactivates latent developmental signaling pathways that determine cell phenotype. Barrett’s esophagus is a squamous-to-columnar epithelial metaplasia caused by reflux esophagitis. Hedgehog (Hh) signaling is active in columnar-lined, embryonic esophagus and inactive in squamous-lined, adult esophagus. We showed previously that Hh signaling is reactivated in Barrett’s metaplasia and overexpression of Sonic hedgehog (SHH) in mouse esophageal squamous epithelium leads to a columnar phenotype. Here, our objective was to identify Hh target genes involved in Barrett’s pathogenesis. By microarray analysis, we found that the transcription factor Foxa2 is more highly expressed in murine embryonic esophagus compared with postnatal esophagus. Conditional activation of Shh in mouse esophageal epithelium induced FOXA2, while FOXA2 expression was reduced in Shh knockout embryos, establishing Foxa2 as an esophageal Hh target gene. Evaluation of patient samples revealed FOXA2 expression in Barrett’s metaplasia, dysplasia, and adenocarcinoma but not in esophageal squamous epithelium or squamous cell carcinoma. In esophageal squamous cell lines, Hh signaling upregulated FOXA2, which induced expression of MUC2, an intestinal mucin found in Barrett’s esophagus, and the MUC2-processing protein AGR2. Together, these data indicate that Hh signaling induces expression of genes that determine an intestinal phenotype in esophageal squamous epithelial cells and may contribute to the development of Barrett’s metaplasia. PMID:25083987

  3. 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

  4. Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

    PubMed Central

    Hirano, Ikuo; Aceves, Seema S.

    2014-01-01

    In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in both the epithelium as well as in the subepithelium where lamina propria (LP) fibrosis, expansion of the muscularis propria and increased vascularity occur. The major clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Important mediators of the process include IL-5, IL-13, TGFβ1, mast cells, fibroblasts and eosinophils. Methods to detect remodeling effects include upper endoscopy, histopathology, barium esophagram, endoscopic ultrasonography, esophageal manometry, and functional luminal imaging. These modalities provide evidence of organ dysfunction that include focal and diffuse esophageal strictures, expansion of the mucosa and subepithelium, esophageal motor abnormalities and reduced esophageal distensibility. Complications of food impaction and perforations of the esophageal wall have been associated with reduction in esophageal caliber and increased esophageal mural stiffness. The therapeutic benefits of topical corticosteroids and elimination diet therapy in resolving mucosal eosinophilic inflammation of the esophagus are evident. Available therapies, however, have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies that include novel, targeted biologic agents have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic endpoints account for the fundamental contributions of esophageal remodeling to overall disease activity. PMID:24813517

  5. Achalasia and Esophageal Motility Disorders

    MedlinePlus

    ... esophagus, and chest wall Lung Cancer Esophageal Cancer Gastroesophageal Reflux Disease Barrett’s Esophagus Chest Wall Tumors Mediastinal Tumors ... Section Navigation Select Topic Lung Cancer Esophageal Cancer Gastroesophageal Reflux Disease Barrett’s Esophagus Chest Wall Tumors Mediastinal Tumors ...

  6. General Information about Esophageal Cancer

    MedlinePlus

    ... Research Esophageal Cancer Treatment (PDQ®)–Patient Version General Information About Esophageal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  7. Molecular pathological diagnosis for early esophageal cancer in Kazakh patients

    PubMed Central

    AWUT, IDIRIS; NIYAZ, MADINIYET; BIEKEMITOUFU, HADETI; ZHANG, ZHU; SHEYHEDIN, ILYAR; HAO, WEN

    2011-01-01

    Chromosome abnormalities in cancer cells occur early in carcinogenesis. We employed DNA probes for the detection of cancer cells in surgical specimens in Kazakh patients with suspected esophageal carcinoma, to analyze the application of this technique during the early diagnosis of esophageal cancer. Comparative analysis was used to compare the results of pathological diagnosis with the results of FISH. We performed esophagofiberscopic biopsy examinations in 50 Kazakh patients with suspected esophageal carcinoma, including 40 males and 10 females, with an average age of 56.8 years. The final diagnosis was esophageal squamous cell carcinoma in 47 patients, and adenocarcinoma, mucinous carcinoma and small cell carcinoma in one patient each. The pathological findings of the biopsy were positive in 45 cases, and false-negative in 5. The sensitivity and specificity of pathological diagnosis were 87.2 and 100%, respectively. Using FISH to examine the same tissues, we found that 48 cases showed aberrant copy numbers in either chromosome 3 or 17, and 2 cases were false-negative, with a sensitivity and specificity of 94.8 and 100%, respectively. The copy numbers of centromeres in chromosome 3 were significantly higher than the copy numbers of centromeres in chromosome 17 (P=0.0001). Compared with biopsy pathology, the FISH test was more sensitive. Being an objective and qualitative method, the technology of molecular pathological diagnosis may effectively increase the early diagnostic rate of esophageal cancer. In addition, the centromere probe in chromosome 3 may be the most sensitive probe for the diagnosis of esophageal cancer in Kazakh patients. PMID:22740949

  8. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false EAS Decoder. 11.33 Section 11.33 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11.33 EAS Decoder. (a) An EAS Decoder must at a minimum be capable of decoding the EAS protocol described in § 11.31, provide the EAS...

  9. Epidemiology of esophageal cancer: Orient to Occident. Effects of chronology, geography and ethnicity.

    PubMed

    Hongo, Michio; Nagasaki, Yutaka; Shoji, Tomotaka

    2009-05-01

    Esophageal adenocarcinoma (EAC) has been rapidly increasing in Western countries during the past half century, especially in white men. Esophageal squamous cell carcinoma (ESCC) used to be the dominant type of esophageal malignancy both in Western and Asian countries. The rapid increase of EAC in Western countries has occurred in parallel with an increased prevalence of gastroesophageal reflux disease (GERD) and its major determinant, obesity. Such an increase in EAC has not yet been observed in Asia, despite a recent increase in prevalence of GERD. In this mini-review, we analyze possible factors influencing such east-west ('Orient to Occident') differences, particularly possible roles of ethnicity and environmental factors, such as Helicobacter pylori infection and nutritional factors, and how these might interact with socioeconomic differences. Development of Barrett's esophagus and esophageal adenocarcinoma appears to be strongly affected by ethnic factors, with populations resident at the west end of the Eurasian continent, such as Anglo-Celtics, being more prone to both conditions. On the other hand, ethnic groups from the eastern and southern ends of Eurasia, such as Chinese, Koreans and Japanese, and Africans might be more prone to developing esophageal squamous cell carcinoma. Future trends will also be discussed. PMID:19646015

  10. Genetic landscape of esophageal squamous cell carcinoma.

    PubMed

    Gao, Yi-Bo; Chen, Zhao-Li; Li, Jia-Gen; Hu, Xue-Da; Shi, Xue-Jiao; Sun, Zeng-Miao; Zhang, Fan; Zhao, Zi-Ran; Li, Zi-Tong; Liu, Zi-Yuan; Zhao, Yu-Da; Sun, Jian; Zhou, Cheng-Cheng; Yao, Ran; Wang, Su-Ya; Wang, Pan; Sun, Nan; Zhang, Bai-Hua; Dong, Jing-Si; Yu, Yue; Luo, Mei; Feng, Xiao-Li; Shi, Su-Sheng; Zhou, Fang; Tan, Feng-Wei; Qiu, Bin; Li, Ning; Shao, Kang; Zhang, Li-Jian; Zhang, Lan-Jun; Xue, Qi; Gao, Shu-Geng; He, Jie

    2014-10-01

    Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications. PMID:25151357

  11. Endoscopic Management of Anastomotic Esophageal Strictures Secondary to Esophageal Atresia.

    PubMed

    Manfredi, Michael A

    2016-01-01

    The reported incidence of anastomotic stricture after esophageal atresia repair has varied in case series from as low as 9% to as high as 80%. The cornerstone of esophageal stricture treatment is dilation with either balloon or bougie. The goal of esophageal dilation is to increase the luminal diameter of the esophagus while also improving dysphagia symptoms. Once a stricture becomes refractory to esophageal dilation, there are several treatment therapies available as adjuncts to dilation therapy. These therapies include intralesional steroid injection, mitomycin C, esophageal stent placement, and endoscopic incisional therapy. PMID:26616905

  12. Usefulness of chromoendoscopy and magnifying narrow band imaging endoscopy for diagnosis of demarcation of adenocarcinoma in Barrett's esophagus.

    PubMed

    Yamashina, Takeshi; Uedo, Noriya; Matsui, Fumi; Ishihara, Ryu; Tomita, Yasuhiko

    2013-05-01

    It is often difficult to accurately delineate the borders and extent of early-stage esophageal adenocarcinoma in patients with Barrett's esophagus using conventional white light endoscopy. Chromoendoscopy enhances the characteristics of the mucosa and improves detection and delineation of small or flat lesions difficult to identify by conventional endoscopy. Magnifying endoscopy with narrow-band imaging (NBI) is a novel endoscopic imaging technology that contrasts the vascular architecture and surface structure of the superficial mucosa. As magnifying NBI can view only a narrow area of the mucosa, this method cannot determine the circumference of the lesion and evaluate its complete extent. Indigocarmine chromoendoscopy is useful for delineating the extent of Barrett's adenocarcinoma. Chromoendoscopy and magnifying NBI are complementary methods, with both being required for the accurate diagnosis of tumor extent in patients with superficial Barrett's esophageal adenocarcinoma.

  13. Esophageal phytobezoar in a horse.

    PubMed

    MacDonald, M H; Richardson, D W; Morse, C C

    1987-12-01

    A 23-year-old Thoroughbred stallion was admitted to the hospital for treatment of acute esophageal obstruction. Clinical examination and contrast radiography confirmed the presence of an esophageal obstruction. The horse was euthanatized, and examination revealed a bolus of feed material occluding the esophageal lumen 6 cm caudal to the thoracic inlet, with underlying necrosis of the esophageal mucosa. A large pulsion diverticulum was identified in the caudocervical portion of the esophagus. Apparently, the phytobezoar was formed within the esophageal diverticulum and subsequently became dislodged, occluding the esophagus.

  14. [Esophageal motility disorders].

    PubMed

    Dughera, L; Battaglia, E; Emanuelli, G

    2001-09-01

    Esophageal motility abnormalities are usually diagnosed when esophageal manometry is performed in patients with unexplained non-cardiac chest pain, non obstructive dysphagia or as a part of the preoperative evaluation for surgery of gastroesophageal reflux. Classification of these abnormalities has been a subject of controversy. These esophageal contraction abnormalities can be separated manometrically from the motor pattern seen in normal subjects, however, their clinical relevance is still unclear and debated. Many patients demonstrate motility abnormalities in the manometry laboratories, but may lack correlation with their presenting symptoms. Medical treatment can decrease symptoms particularly chest pain or acid reflux but there is no significant changes in the manometric patterns. Such motor abnormalities may not reflect a true disease state, but they could be markers of other abnormalities and they can modify the initial manometric findings in time.

  15. National Esophageal Atresia Register.

    PubMed

    Sfeir, Rony; Michaud, Laurent; Sharma, Duyti; Richard, Florence; Gottrand, Frédéric

    2015-12-01

    National Esophageal Atresia was created in 2008 by the National Reference Center for Esophageal Congenital Abnormalities created in 2006. Primary goal was estimation of live birth prevalence in France. A national network of surgeons and pediatricians was initiated and entire teams dealing with esophageal atresia accepted to participate in an exhaustive national register. A questionnaire was validated by a national committee and data were centralized in our center. Scientific exploitation showed that such database is useful for health authorities as for medical professionals. Live birth prevalence in France is at 1.9/10,000 births. Prenatal diagnosis is more common but its effect on prevalence is not yet fully understood. Associated congenital abnormalities are frequent and major malformations with termination of pregnancy can influence prevalence. PMID:26642387

  16. Minimally invasive surgery for esophageal achalasia

    PubMed Central

    Chen, Huan-Wen

    2016-01-01

    Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow’s relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia. PMID:27499977

  17. Management of patients with combined tracheoesophageal fistula, esophageal atresia, and duodenal atresia

    PubMed Central

    Nabzdyk, Christoph S.; Chiu, Bill; Jackson, Carl-Christian; Chwals, Walter J.

    2014-01-01

    INTRODUCTION Patients with combined esophageal atresia (EA), tracheoesophageal fistula (TEF), and duodenal atresia (DA) pose a rare management challenge. PRESENTATION OF CASE Three patients with combined esophageal atresia (EA), tracheoesophageal fistula (TEF), and duodenal atresia safely underwent a staged approach inserting a gastrostomy tube and repairing the EA/TEF first followed by a duodenoduodenostomy within one week. None of the patients suffered significant pre- or post-operative complications and our follow-up data (between 12 and 24 months) suggest that all patients eventually outgrow their reflux and respiratory symptoms. DISCUSSION While some authors support repair of all defects in one surgery, we recommend a staged approach. A gastrostomy tube is placed first for gastric decompression before TEF ligation and EA repair can be safely undertaken. The repair of the DA can then be performed within 3–7 days under controlled circumstances. CONCLUSION A staged approach of inserting a gastrostomy tube and repairing the EA/TEF first followed by a duodenoduodenostomy within one week resulted in excellent outcomes. PMID:25460495

  18. Assessing esophageal dysphagia.

    PubMed

    Kruger, Danielle

    2014-05-01

    Dysphagia, or difficulty swallowing, is a common problem. Although most cases are attributable to benign disease processes, dysphagia is also a key symptom in several malignancies, making it an important symptom to evaluate. The differential diagnosis of dysphagia requires an understanding of deglutition, in particular the oropharyngeal versus esophageal stages. Stroke is the leading cause of oropharyngeal dysphagia, which is common in older adults and frequently presents as part of a broader complex of clinical manifestations. In esophageal dysphagia, difficulty swallowing is often the main complaint and is caused by localized neuromuscular disorders or obstructive lesions.

  19. 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.

  20. Adenocarcinoma of the prostrate

    SciTech Connect

    Bruce, A.W.; Trachtenberg, J.

    1987-01-01

    This books contains 13 chapters. Some of the chapter titles are: Imaging Techniques in the Diagnosis and Pelvic Staging of Prostatic Cancer; Interstitial Radiotherapy; The Case for External Beam Radiotherapy of Certain Adenocarcinomas of the Prostate; and Chemotherapy of Prostatic Cancer.

  1. 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

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

    PubMed

    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

    2015-08-01

    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

  3. Outcomes in patients with brain metastasis from esophageal carcinoma

    PubMed Central

    Kothari, Nishi; Mellon, Eric; Hoffe, Sarah E.; Frakes, Jessica; Shridhar, Ravi; Pimiento, Jose; Meredith, Ken; Tran, Nam D.; Saeed, Nadia

    2016-01-01

    Background Brain metastases from esophageal carcinoma have historically been rare and associated with poor prognosis. With improvements in systemic disease control, the incidence of brain metastases is expected to rise. To better inform management decisions, we sought to identify factors associated with survival in patients with brain metastasis from esophageal cancer. Methods We retrospectively identified 49 patients with brain metastasis from stage I–IV primary esophageal cancer treated with surgery, radiation, or a combination of modalities at our tertiary referral center between 1998 and 2015. Medical records were reviewed to collect demographic and clinical information. Results Median age at diagnosis of the primary esophageal cancer was 60 years. Forty-one (84%) patients were male and forty patients (82%) had adenocarcinoma. Median overall survival (MS) following esophageal cancer diagnosis was 24 months (range, 3–71 months), and median survival after the identification of brain metastases was 5 months (range, 1–52 months). On univariate analysis, only patients with poor Karnofsky performance status (KPS <70), recursive partitioning analysis (RPA) classification (III), or 3 or more brain metastases were found to have worsened survival after the diagnosis of brain metastases (all P<0.01). Factors not associated with survival were age, gender, histology (adenocarcinoma vs. other), palliative-intent treatment of the primary tumor, time to diagnosis of brain metastases from initial diagnosis, uncontrolled primary tumor at time of brain metastasis diagnosis, or extracranial metastases. On multivariate analysis (MVA, KPS excluded), patients with RPA class I (MS, 14.6 months) or II (MS, 5.0 months) disease had significantly improved overall survival compared to class III disease (MS, 1.6 months, P<0.01). Also on MVA, patients with 1 (MS, 10.7 months) or 2 (MS, 4.7 months) brain metastases had significantly improved overall survival compared to patients with 3

  4. Esophagitis in Adolescents.

    PubMed

    Putnam, Philip E

    2016-01-01

    Esophagitis is the end result of a variety of insults to epithelial homeostasis. Eosinophilic esophagitis is a manifestation of non-IgE-mediated food allergy that most commonly affects the esophagus of males who have other atopic phenomena. Reflux esophagitis reflects repeated exposure to acidic gastric contents because of failure of the normal protections afforded by the LES. Because certain histologic features can be present in either condition, endoscopic biopsy alone does not distinguish them. Their symptoms overlap, but the treatment options are very different, such that making a formal diagnosis by following consensus guidelines is essential. A treatment protocol designed to manage the inflammation by controlling the provocative factors (acid for GERD and food antigens for EoE) or suppressing the inflammation (ie, topical steroids for EoE) should result in normalization of the mucosa and resolution of symptoms. Eosinophilic esophagitis is a chronic condition that rarely remits spontaneously, so any therapeutic modality will need to be continued indefinitely. PMID:27363230

  5. 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

  6. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false EAS Decoder. 11.33 Section 11.33 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11.33 EAS Decoder. (a) An EAS Decoder must at a minimum be capable of providing the EAS monitoring functions described in § 11.52, decoding...

  7. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false EAS Decoder. 11.33 Section 11.33 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11.33 EAS Decoder. (a) An EAS Decoder must at a minimum be capable of providing the EAS monitoring functions described in § 11.52, decoding...

  8. Adenocarcinoma of the GEJ: gastric or oesophageal cancer?

    PubMed

    Rüschoff, J

    2012-01-01

    According to WHO (2010) adenocarcinomas of the esophagogastric junction (GEJ) are defined as tumors that cross the most proximal extent of the gastric folds regardless of where the bulk of the tumor lies. In addition, these neoplasms are now classified as esophageal cancers by UICC (2010). Recent studies, however, revealed two types of carcinogenesis in the distal oesophagus and at the GEJ, one of intestinal type (about 80 %) and the other of gastric type (about 20 %). These are characterized by marked differences in morphology, tumor stage at diagnosis, and prognosis. Furthermore, both cancer types show different targetable biomarker expression profiles such as Her2 in the intestinal and EGFR in the non-intestinal pathway indicating new therapy options. Due to the fact that carcinomas of the intestinal pathway were typically associated with Barrett's mucosa which was not the case in the non-intestinal-type tumors, this challenges the paradigm "no goblets no Barrett's". Moreover, even the cancer risk of intestinal-type metaplasia has seriously been questioned by a Danish population-based study where Barrett's mucosa turned out to be only a weak indicator of esophageal and GEJ cancer (1 case in 860 patients years). Thus, two biologically different types of cancer arise at the GEJ-esophageal and gastric type that open distinctive targeted treatment options and also question our current concept about the diagnostics of potential precursor lesions as well as the associated screening and surveillance strategy.

  9. Effect of gastroesophageal reflux on esophageal speech.

    PubMed

    Mathis, J G; Lehman, G A; Shanks, J C; Blom, E D; Brunelle, R L

    1983-12-01

    Gastroesophageal reflux has been incriminated as a factor-inhibiting acquisition of esophageal speech after laryngectomy. Fourteen proficient esophageal speakers and 10 nonproficient speakers underwent esophageal manometry, esophageal pH probe testing, and Bernstein acid perfusion testing. Additionally, 175 laryngectomized members of Lost Chord Clubs answered mailed questionnaires about the frequency of reflux symptoms. Nonproficient and proficient esophageal speakers had a similar frequency of gastroesophageal reflux by pH probe testing, esophageal mucosal acid sensitivity by Bernstein testing, lower esophageal sphincter pressures, and gastroesophageal reflux symptoms. Gastroesophageal reflux does not appear to be a major factor in preventing esophageal speech.

  10. [Low grade sinonasal adenocarcinoma].

    PubMed

    Sayilgan, Ayşe Tülay; Kamali, Gülçin; Ozcan, Deniz; Emre, Funda; Hatıpoğlu, Ayşe

    2012-01-01

    Sinonasal adenocarcinoma is a rare neoplasm which is classified as 'intestinal' or 'nonintestinal' type, depending on its resemblance to gastrointestinal mucosa. These tumors are associated with occupational and environmental carcinogens. In this study, a fifty-year-old oil-painter male patient with a low-grade nonintestinal type sinonasal adenocarcinoma originating from the left middle concha and ethmoid sinus is presented. Microscopical examination revealed many infiltrative glandular structures, most of which were cystically dilated and some of which were smaller in diameter, arranged back to back in loose fibrous stroma as well as intraglandular papillary and micropapillary structures forming complex branches or a cribriform pattern. The glands were lined by epithelial cells that were faintly eosinophilic and relatively abundant cubical/ cylinderical cytoplasms and mildly pleomorphic round/oval nuclei, with rare mitotic figures. Intraluminal and focally intracytoplasmic mucin was demonstrated with Alcian Blue, mucicarmin and PAS stains. Immunohistochemically, tumor cells were strongly and diffusely positive with CK7; focally and weakly positive with CK20 and negative with CDX2 in accordance with the nonintestinal type. S-100, Actin and p63, applied for investigating the myoepithelial and salivary glandular origins, were all negative. Prognostic markers, TTF-1 and p53 were negative; while the Ki-67 index was 2%. The fact that intestinal type sinonasal adenocarcinomas are generally high grade, while nonintestinal tumors are histologically low grade makes this morphological and immunohistochemical-based classification valuable in predicting the prognosis of the disease. In addition to the morphological and immunohistochemical findings, clinical information stands out in the differentiation of the tumor from benign or malignant primary lesions or metastatic adenocarcinoma.

  11. Predictive factors for complications in children with esophageal atresia and tracheoesophageal fistula.

    PubMed

    Shah, R; Varjavandi, V; Krishnan, U

    2015-04-01

    The objective of this study was to describe the incidence of complications in children with esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) at a tertiary pediatric hospital and to identify predictive factors for their occurrence. A retrospective chart review of 110 patients born in or transferred to Sydney Children's Hospital with EA/TEF between January 1999 and December 2010 was done. Univariate and multivariate regression analyses were performed to identify predictive factors for the occurrence of complications in these children. From univariate analysis, early esophageal stricture formation was more likely in children with 'long-gap' EA (odds ratio [OR] = 16.32). Patients with early strictures were more likely to develop chest infections (OR = 3.33). Patients with severe tracheomalacia were more likely to experience 'cyanotic/dying' (OR = 180) and undergo aortopexy (OR = 549). Patients who had gastroesophageal reflux disease were significantly more likely to require fundoplication (OR = 10.83) and undergo aortopexy (OR = 6.417). From multivariate analysis, 'long-gap' EA was a significant predictive factor for late esophageal stricture formation (P = 0.007) and for gastrostomy insertion (P = 0.001). Reflux was a significant predictive factor for requiring fundoplication (P = 0.007) and gastrostomy (P = 0.002). Gastrostomy insertion (P = 0.000) was a significant predictive factor for undergoing fundoplication. Having a prior fundoplication (P = 0.001) was a significant predictive factor for undergoing a subsequent aortopexy. Predictive factors for the occurrence of complications post EA/TEF repair were identified in this large single centre pediatric study.

  12. Eosinophilic esophagitis: current treatment.

    PubMed

    Redd, Matthew; Schey, Ron

    2013-03-01

    Eosinophilic esophagitis (EoE) is a relatively new entity with a significant amount of increased recognition over the last decade. The mainstay treatments of EoE are designed to eliminate the causative allergens or to reduce their effects on the esophageal mucosa. Common treatments include dietary modification, proton pump inhibitors, systemic and topical corticosteroids, and endoscopic treatments. As the pathogenesis of EoE is explored, new and novel treatments are being studied that target specific pathways and chemokines identified in as precipitating agents of EoE. This is a rapidly evolving field with significant ongoing research and clinical studies. Our review will therefore focus on current and novel treatment approaches to the disease.

  13. Prevalence of Esophageal Atresia among 18 International Birth Defects Surveillance Programs

    PubMed Central

    Nassar, Natasha; Leoncini, Emanuele; Amar, Emmanuelle; Arteaga-Vázquez, Jazmín; Bakker, Marian K.; Bower, Carol; Canfield, Mark A.; Castilla, Eduardo E.; Cocchi, Guido; Correa, Adolfo; Csáky-Szunyogh, Melinda; Feldkamp, Marcia L.; Khoshnood, Babak; Landau, Danielle; Lelong, Nathalie; López-Camelo, Jorge S.; Lowry, R. Brian; McDonnell, Robert; Merlob, Paul; Métneki, Julia; Morgan, Margery; Mutchinick, Osvaldo M.; Palmer, Miland N.; Rissmann, Anke; Siffel, Csaba; Sìpek, Antonin; Szabova, Elena; Tucker, David; Mastroiacovo, Pierpaolo

    2015-01-01

    BACKGROUND The prevalence of esophageal atresia (EA) has been shown to vary across different geographical settings. Investigation of geographical differences may provide an insight into the underlying etiology of EA. METHODS The study population comprised infants diagnosed with EA during 1998 to 2007 from 18 of the 46 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research. Total prevalence per 10,000 births for EA was defined as the total number of cases in live births, stillbirths, and elective termination of pregnancy for fetal anomaly (ETOPFA) divided by the total number of all births in the population. RESULTS Among the participating programs, a total of 2943 cases of EA were diagnosed with an average prevalence of 2.44 (95% confidence interval [CI], 2.35–2.53) per 10,000 births, ranging between 1.77 and 3.68 per 10,000 births. Of all infants diagnosed with EA, 2761 (93.8%) were live births, 82 (2.8%) stillbirths, 89 (3.0%) ETOPFA, and 11 (0.4%) had unknown outcomes. The majority of cases (2020, 68.6%), had a reported EA with fistula, 749 (25.5%) were without fistula, and 174 (5.9%) were registered with an unspecified code. CONCLUSIONS On average, EA affected 1 in 4099 births (95% CI, 1 in 3954–4251 births) with prevalence varying across different geographical settings, but relatively consistent over time and comparable between surveillance programs. Findings suggest that differences in the prevalence observed among programs are likely to be attributable to variability in population ethnic compositions or issues in reporting or registration procedures of EA, rather than a real risk occurrence difference. PMID:22945024

  14. Esophageal carcinoma: CT findings

    SciTech Connect

    Quint, L.E.; Glazer, G.M.; Orringer, M.B.; Gross, B.H.

    1985-04-01

    Preoperative CT scans of 33 patients with esophageal cancer were reviewed to assess staging accuracy and define the role of CT in patients being considered for transhiatal blunt esophagectomy. Surgical and pathological verification was obtained in all cases. Only 13 tumors were staged correctly according to the TNM classification. In addition, CT was not useful in assessing resectability because of its low accuracy in evaluating aortic invasion and the fact that few patients had tracheobronchial or aortic invasion or hepatic metastases at presentation.

  15. Hypnotherapy for Esophageal Disorders.

    PubMed

    Riehl, Megan E; Keefer, Laurie

    2015-07-01

    Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms--visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome. PMID:26046715

  16. Staging Early Esophageal Cancer.

    PubMed

    Old, O J; Isabelle, M; Barr, H

    2016-01-01

    Staging esophageal cancer provides a standardized measure of the extent of disease that can be used to inform decisions about therapy and guide prognosis. For esophageal cancer, the treatment pathways vary greatly depending on stage of disease, and accurate staging is therefore crucial in ensuring the optimal therapy for each patient. For early esophageal cancer (T1 lesions), endoscopic resection can be curative and simultaneously gives accurate staging of depth of invasion. For tumors invading the submucosa or more advanced disease, comprehensive investigation is required to accurately stage the tumor and assess suitability for curative resection. A combined imaging approach of computed tomography (CT), positron emission tomography (PET), and endoscopic ultrasound (EUS) offers complementary diagnostic information and gives the greatest chance of accurate staging. Staging laparoscopy can identify peritoneal disease and small superficial liver lesions that could be missed on CT or PET, and alters management in up to 20 % of patients. Optical diagnostic techniques offer the prospect of further extending the possibilities of endoscopic staging in real time. Optical coherence tomography can image superficial lesions and could provide information on depth of invasion for these lesions. Real-time lymph node analysis using optical diagnostics such as Raman spectroscopy could be used to support immediate endoscopic therapy without waiting for results of cytology or further investigations. PMID:27573772

  17. Diagnostic marker signature for esophageal cancer from transcriptome analysis.

    PubMed

    Warnecke-Eberz, Ute; Metzger, Ralf; Hölscher, Arnulf H; Drebber, Uta; Bollschweiler, Elfriede

    2016-05-01

    Esophageal cancer is often diagnosed at an advanced stage. Diagnostic markers are needed for achieving a cure in esophageal cancer detecting and treating tumor cells earlier. In patients with locally advanced squamous cell carcinoma of the esophagus (ESCC), we profiled the gene expression of ESCC compared to corresponding normal biopsies for diagnostic markers by genome microarrays. Profiling of gene expression identified 4844 genes differentially expressed, 2122 upregulated and 2722 downregulated in ESCC. Twenty-three overexpressed candidates with best scores from significance analysis have been selected for further analysis by TaqMan low-density array-technique using a validation cohort of 40 patients. The verification rate was 100 % for ESCC. Twenty-two markers were additionally overexpressed in adenocarcinoma of the esophagus (EAC). The markers significantly overexpressed already in earlier tumor stages (pT1-2) of both histological subtypes (n = 19) have been clustered in a "diagnostic signature": PLA2G7, PRAME, MMP1, MMP3, MMP12, LIlRB2, TREM2, CHST2, IGFBP2, IGFBP7, KCNJ8, EMILIN2, CTHRC1, EMR2, WDR72, LPCAT1, COL4A2, CCL4, and SNX10. The marker signature will be translated to clinical practice to prove its diagnostic impact. This diagnostic signature may contribute to the earlier detection of tumor cells, with the aim to complement clinical techniques resulting in the development of better detection of concepts of esophageal cancer for earlier therapy and more favorite prognosis. PMID:26631031

  18. [Endoscopic Therapy for Esophageal Cancer].

    PubMed

    Sakai, Makoto; Kuwano, Hiroyuki

    2016-07-01

    Endoscopic treatment for esophageal neoplasms includes endoscopic resection, argon plasma coagulation(APC), photodynamic therapy( PDT) and stent placement. Endoscopic resection is widely used as an effective, less invasive treatment for superficial esophageal carcinoma in Japan. APC is considered to be safe and effective treatment for superficial esophageal carcinoma which cannot be resected endoscopically because of severe comorbidities, as well as for local recurrence after endoscopic resection or chemoradiotherapy. PDT is thought to be an effective option as salvage treatment for local failure after chemoradiotherapy. Stent placement mainly using self-expanding metallic stents have been used as a minimally invasive and effective modality for the palliative treatment of malignant esophageal obstruction. Endoscopic treatment is expected to have more important role in the treatment of esophageal neoplasms in the future. PMID:27440040

  19. Pancreatic adenocarcinoma: Outstanding problems

    PubMed Central

    Zakharova, Olga P; Karmazanovsky, Grigory G; Egorov, Viacheslav I

    2012-01-01

    Pancreatic adenocarcinoma remains the fourth leading cause of cancer-related death and is one of the most aggressive malignant tumors with an overall 5-year survival rate of less than 4%. Surgical resection remains the only potentially curative treatment but is only possible for 15%-20% of patients with pancreatic adenocarcinoma. About 40% of patients have locally advanced nonresectable disease. In the past, determination of pancreatic cancer resectability was made at surgical exploration. The development of modern imaging techniques has allowed preoperative staging of patients. Institutions disagree about the criteria used to classify patients. Vascular invasion in pancreatic cancers plays a very important role in determining treatment and prognosis. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer and a unified definition of borderline resectable pancreatic cancer is also lacking. Thus, there is much room for improvement in all aspects of treatment for pancreatic cancer. Multi-detector computed tomography has been widely accepted as the imaging technique of choice for diagnosing and staging pancreatic cancer. With improved surgical techniques and advanced perioperative management, vascular resection and reconstruction are performed more frequently; patients thought once to be unresectable are undergoing radical surgery. However, when attempting heroic surgery, a realistic approach concerning the patient’s age and health status, probability of recovery after surgery, perioperative morbidity and mortality and life quality after tumor resection is necessary. PMID:22655124

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

    PubMed

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

    2014-05-15

    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.

  1. Genetic diagnosis of patients with esophageal cancer using FISH

    PubMed Central

    AWUT, IDIRIS; NIYAZ, MADINIYET; HUIZHONG, XIE; BIEKEMITOUFU, HADETI; YAN, ZHANG HONG; ZHU, ZHANG; SHEYHEDIN, ILYAR; CHANGMIN, ZHANG; WEI, ZHANGLI; HAO, WEN

    2010-01-01

    This study aimed to the clarify the diagnostic efficacy of fluorescence in situ hybridization (FISH) in Kazakh patients with esophageal cancer (EC). FISH was compared with the pathological examination of biopsy specimens with DNA probes. We enrolled 20 patients, of which 15 were males and 5 females, with an average age of 58.3 years, who had abnormal esophaguses on barium radiological digital imaging. Touch preparations were performed on biopsy specimens from all of the patients and were examined using FISH for chromosomal abnormalities. We compared the FISH results with the pathology slides stained with hematoxylin and eosin. Classification, according to pathology, identified 2 cases of class II, 3 cases of IIIa, 1 case of IIIb, 2 cases of IV, 12 cases of class V and no cases of class I. The cases classified as class IIIb or higher were considered to be positive for cancer. Using histopathology, 10 cases were diagnosed with squamous cell carcinoma and 5 were diagnosed as adenocarcinoma, with one case being false-negative. Thus, the sensitivity of the pathological examination was 93% and the specificity was 100%. Using FISH, 16 cases showed aberrant copy numbers in either chromosome 3 or 17. By comparison, pathology did not reveal any false-positive or false-negative cases with a sensitivity and specificity of 100%. The centromeres of chromosome 3 copy numbers was significantly higher (p=0.035) than the centromeres of chromosome 17. Our study compared FISH to diagnose aneusomic esophageal cancer cells with the pathology of biopsied tissue. Our findings suggest that FISH is a useful and objective assay for the detection of malignant cells of esophageal cancer. In our study, the centromeres of chromosome 3 was the more sensitive probe for the diagnosis of esophageal cancer in Kazakh patients. PMID:22966385

  2. 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.

  3. [Prevalence of erosive esophagitis and peptic esophageal strictures].

    PubMed

    Vasilevskiĭ, D I; Skurikhin, S S; Luft, A V; Mednikov, S N; Silant'ev, D S; Kulagin, V I; Dvoretskiĭ, S Iu; Bagnenko, S F

    2015-01-01

    Gastroesophageal reflux disease is a widespread among population in economically developed countries including Russia. It was analyzed the results of 34 903 endoscopic examinations of upper gastrointestinal tract in ethnically and socially homogeneous population of Leningrad region with symptoms of gastric dispepsia. Procedures were performed for the period 2007-2013. Prevalence of erosive esophagitis was 4.9%. Peptic esophageal strictures due to chronic reflux-associated inflammation were revealed in 0.2% of examined patients (3.7% of patients with erosive esophagitis). Obtained data allow to considergastroesophageal reflux disease as a socially significant problem in Russia requiring close attention and further study.

  4. Intraluminal esophageal diverticulum.

    PubMed

    Funakoshi, O; Soma, Y; Takasugi, T; Munakata, A; Yoshida, Y

    1990-02-01

    An intraluminal esophageal diverticulum (IED) is an uncommon entity defined as a double-layered mucosal pouch lying within the lumen of the esophagus. Its characteristic radiological finding is an intraluminal barium collection surrounded by a radiolucent halo. True IED, which is different from a transient radiological artifact, has not been previously reported in the international literature. This article describes the first case of true IED. Differential diagnosis between a true lesion and a transient flow artifact on barium meal is discussed. PMID:2106464

  5. Normal exon copy number of the GLI2 and GLI3 genes in patients with esophageal atresia.

    PubMed

    Bednarczyk, D; Smigiel, R; Patkowski, D; Laczmanska, I; Lebioda, A; Laczmanski, L; Sasiadek, M M

    2013-01-01

    Esophageal atresia (EA) is a congenital developmental defect of the alimentary tract concerning the interruption of the esophagus with or without connection to the trachea. The incidence of EA is 1 in 3000-3500 of live-born infants, and occurs in both isolated and syndromic (in combination with abnormalities in other organ systems) forms. The molecular mechanisms underlying the development of EA are poorly understood. Knockout studies in mice indicate that genes like Sonic hedgehog, Gli2, and Gli3 play a role in the etiology of EA. These facts led us to hypothesize that Sonic hedgehog-GLI gene rearrangements are associated with EA in humans. To test this hypothesis, we screened patients with isolated and syndromic EA for GLI2 and/or GLI3 microrearrangements using methods to estimate the copy number (Multiplex Ligation-dependent Probe Amplification, real-time polymerase chain reaction). To our best knowledge this is the first study assessing copy number of GLI2 and GLI3 genes in patients with EA. PMID:23442119

  6. Esophageal Lipoma: A Rare Tumor

    PubMed Central

    Feldman, Jeremy; Tejerina, Manfred; Hallowell, Michael

    2012-01-01

    Esophageal lipomas are rare tumors, making up 0.4% of all digestive tract benign neoplasms. Most of these lesions are clinically silent as a result of their small size, however, the majority of lesions over 4 cm have been reported to cause dysphagia, regurgitation and/or epigastralgia. We report a case of a 53 year-old African American female who presented with dysphagia. Computed tomography of the chest and esophagram confirmed esophageal lipoma as the cause of the patient’s symptoms. Accurately diagnosing an esophageal lipoma is crucial in order to rule out potential malignant lesions, relieve patient symptoms and plan the appropriate treatment. PMID:23365708

  7. Eosinophilic gastroenteritis with esophageal involvement.

    PubMed

    Dobbins, J W; Sheahan, D G; Behar, J

    1977-06-01

    A patient with a lifelong history of asthma and hay fever was investigated because of symptoms of esophageal spasm. Esophageal biopsies revealed elongated papillae and basal zone hyperplasia of the epithelial layer with eosinophilic infiltration of the lamina propria and muscularis mucosae. There was no evidence of reflux. Small bowel biopsies revealed a flat mucosal pattern with absent or blunted villi, tall columar surface epithelium, and eosinophilic infiltration of the lamina propria. He did not respond to a gluten-free diet. This patient is thought to have eosinophilic gatroenteritis with esophageal involvement, the first such case reported.

  8. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

    When radiation therapy is used for palliation of obstruction in patients with advanced esophageal carcinoma, an improvement in dysphagia can be expected in approximately 50% of patients. Major objective responses have rarely been quantitied but, in one study, were seen in 33% patients. Recurrence of dysphagia is usually seen within 2-6 months of treatment. Radiation toxicities and complications, even when used with palliative intent, can be substantial and include esophagitis, tracheoesophageal or esophageal-aortic fistula, mediastinitis, hemorrhage, pneumonitis, and myelosuppression. (JMT)

  9. 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.

  10. Secondary prevention of esophageal squamous cell carcinoma in areas where smoking, alcohol, and betel quid chewing are prevalent.

    PubMed

    Chung, Chen-Shuan; Lee, Yi-Chia; Wang, Cheng-Ping; Ko, Jenq-Yuh; Wang, Wen-Lun; Wu, Ming-Shiang; Wang, Hsiu-Po

    2010-06-01

    Esophageal cancer is ranked as the sixth most common cause of cancer death worldwide and has a substantial effect on public health. In contrast to adenocarcinoma arising from Barrett's esophagus in Western countries, the major disease phenotype in the Asia-Pacific region is esophageal squamous cell carcinoma which is attributed to the prevalence of smoking, alcohol, and betel quid chewing. Despite a multidisciplinary approach to treating esophageal cancer, the outcome remains poor. Moreover, field cancerization reveals that esophageal squamous cell carcinoma is closely linked with the development of head and neck cancers that further sub-optimize the treatment of patients. Therefore, preventive strategies are of paramount importance to improve the prognosis of this dismal disease. Since obstacles exist for primary prevention via risk factor elimination, the current rationale for esophageal cancer prevention is to identify high-risk groups at earlier stages of the disease, and encourage them to get a confirmatory diagnosis, prompt treatment, and intensive surveillance for secondary prevention. Novel biomarkers for identifying specific at-risk populations are under extensive investigation. Advances in image-enhanced endoscopy do not just substantially improve our ability to identify small precancerous or cancerous foci, but can also accurately predict their invasiveness. Research input from the basic sciences should be translated into preventive measures in order to decrease the disease burden of esophageal cancer.

  11. 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.

  12. Association of Esophageal Inflammation, Obesity and Gastroesophageal Reflux Disease: From FDG PET/CT Perspective

    PubMed Central

    Lee, Yi-Chia; Wang, Shan-Ying; Chiu, Han-Mo; Tu, Chia-Hung; Wang, Hsiu-Po; Lin, Jaw-Town; Wu, Ming-Shiang; Yang, Wei-Shiung

    2014-01-01

    Objective Gastroesophageal reflux disease (GERD) is associated with bothersome symptoms and neoplastic progression into Barrett's esophagus and esophageal adenocarcinoma. We aim to determine the correlation between GERD, esophageal inflammation and obesity with 18F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT). Methods We studied 458 subjects who underwent a comprehensive health check-up, which included an upper gastrointestinal endoscopy, FDG PET/CT and complete anthropometric measures. GERD symptoms were evaluated with Reflux Disease Questionnaire. Endoscopically erosive esophagitis was scored using the Los Angeles classification system. Inflammatory activity, represented by standardized uptake values (SUVmax) of FDG at pre-determined locations of esophagus, stomach and duodenum, were compared. Association between erosive esophagitis, FDG activity and anthropometric evaluation, including body mass index (BMI), waist circumference, visceral and subcutaneous adipose tissue volumes were analyzed. Results Subjects with erosive esophagitis (n = 178, 38.9%) had significantly higher SUVmax at middle esophagus (2.69±0.74 vs. 2.41±0.57, P<.001) and esophagogastric junction (3.10±0.89 vs. 2.38±0.57, P<.001), marginally higher at upper esophageal sphincter (2.29±0.42 vs. 2.21±0.48, P = .062), but not in stomach or duodenum. The severity of erosive esophagitis correlated with SUVmax and subjects with Barrett's esophagus had the highest SUVmax at middle esophagus and esophagogastric junction. Heartburn positively correlated with higher SUVmax at middle oesophagus (r = .262, P = .003). Using multivariate regression analyses, age (P = .027), total cholesterol level (P = .003), alcohol drinking (P = .03), subcutaneous adipose tissue (P<.001), BMI (P<.001) and waist circumference (P<.001) were independently associated with higher SUVmax at respective esophageal locations. Conclusions Esophageal inflammation

  13. Esophageal Intramural Pseudodiverticulosis and Concomitant Eosinophilic Esophagitis: A Case Series.

    PubMed

    Scaffidi, Michael A; Garg, Ankit; Ro, Brandon; Wang, Christopher; Yang, Tony T C; Plener, Ian S; Grin, Andrea; Colak, Errol; Grover, Samir C

    2016-01-01

    Background. Esophageal intramural pseudodiverticulosis (EIPD) is an idiopathic benign chronic disease characterized by flask-like outpouchings of the esophageal wall. It is unknown whether there is a genuine association between EIPD and eosinophilic esophagitis (EoE). Aims. To investigate a possible relationship between EIPD and EoE. Methods. Patients with radiographic or endoscopic evidence of pseudodiverticulosis were identified from the database at a single academic center. Cases were analyzed in three areas: clinical information, endoscopic findings, and course. Results. Sixteen cases of esophageal pseudodiverticulosis were identified. Five patients had histologic evidence of eosinophilic esophagitis. Patients with EoE had pseudodiverticula in the mid-to-distal esophagus while those with EIPD had pseudodiverticula predominantly in the proximal esophagus (p < 0.001). EoE with pseudodiverticulosis occurred in younger patients (p < 0.019). Food bolus obstructions were more common in patients with EoE and pseudodiverticulosis than in EIPD (p < 0.034). Conclusions. This is the first case series supporting a potential association between EoE and pseudodiverticulosis. We also identify characteristic features of pseudodiverticulosis that may raise clinical suspicion of underlying eosinophilic esophagitis. PMID:27648438

  14. Esophageal Intramural Pseudodiverticulosis and Concomitant Eosinophilic Esophagitis: A Case Series

    PubMed Central

    Scaffidi, Michael A.; Garg, Ankit; Ro, Brandon; Wang, Christopher; Yang, Tony T. C.; Plener, Ian S.; Grin, Andrea; Colak, Errol

    2016-01-01

    Background. Esophageal intramural pseudodiverticulosis (EIPD) is an idiopathic benign chronic disease characterized by flask-like outpouchings of the esophageal wall. It is unknown whether there is a genuine association between EIPD and eosinophilic esophagitis (EoE). Aims. To investigate a possible relationship between EIPD and EoE. Methods. Patients with radiographic or endoscopic evidence of pseudodiverticulosis were identified from the database at a single academic center. Cases were analyzed in three areas: clinical information, endoscopic findings, and course. Results. Sixteen cases of esophageal pseudodiverticulosis were identified. Five patients had histologic evidence of eosinophilic esophagitis. Patients with EoE had pseudodiverticula in the mid-to-distal esophagus while those with EIPD had pseudodiverticula predominantly in the proximal esophagus (p < 0.001). EoE with pseudodiverticulosis occurred in younger patients (p < 0.019). Food bolus obstructions were more common in patients with EoE and pseudodiverticulosis than in EIPD (p < 0.034). Conclusions. This is the first case series supporting a potential association between EoE and pseudodiverticulosis. We also identify characteristic features of pseudodiverticulosis that may raise clinical suspicion of underlying eosinophilic esophagitis. PMID:27648438

  15. Esophageal Intramural Pseudodiverticulosis and Concomitant Eosinophilic Esophagitis: A Case Series

    PubMed Central

    Scaffidi, Michael A.; Garg, Ankit; Ro, Brandon; Wang, Christopher; Yang, Tony T. C.; Plener, Ian S.; Grin, Andrea; Colak, Errol

    2016-01-01

    Background. Esophageal intramural pseudodiverticulosis (EIPD) is an idiopathic benign chronic disease characterized by flask-like outpouchings of the esophageal wall. It is unknown whether there is a genuine association between EIPD and eosinophilic esophagitis (EoE). Aims. To investigate a possible relationship between EIPD and EoE. Methods. Patients with radiographic or endoscopic evidence of pseudodiverticulosis were identified from the database at a single academic center. Cases were analyzed in three areas: clinical information, endoscopic findings, and course. Results. Sixteen cases of esophageal pseudodiverticulosis were identified. Five patients had histologic evidence of eosinophilic esophagitis. Patients with EoE had pseudodiverticula in the mid-to-distal esophagus while those with EIPD had pseudodiverticula predominantly in the proximal esophagus (p < 0.001). EoE with pseudodiverticulosis occurred in younger patients (p < 0.019). Food bolus obstructions were more common in patients with EoE and pseudodiverticulosis than in EIPD (p < 0.034). Conclusions. This is the first case series supporting a potential association between EoE and pseudodiverticulosis. We also identify characteristic features of pseudodiverticulosis that may raise clinical suspicion of underlying eosinophilic esophagitis.

  16. Caustic ingestion and esophageal function

    SciTech Connect

    Cadranel, S.; Di Lorenzo, C.; Rodesch, P.; Piepsz, A.; Ham, H.R. )

    1990-02-01

    The aim of the present study was to investigate esophageal motor function by means of krypton-81m esophageal transit scintigraphy and to compare the results with the functional and morphological data obtained by means of triple lumen manometry and endoscopy. In acute and subacute stages of the disease, all clinical, anatomical, and functional parameters were in good agreement, revealing significant impairment. In chronic stages, the severity of the dysphagia was not correlated to the importance of the residual stenosis. Conversely, 81mKr esophageal transit and manometric's findings were in good agreement with the clinical symptoms, during the entire follow-up period ranging between 3 months to 7 years. The 81mKr test is undoubtedly the easiest and probably the most physiological technique currently available for long-term functional evaluation of caustic esophagitis.

  17. 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.

  18. Understanding the sensory irregularities of esophageal disease.

    PubMed

    Farmer, Adam D; Brock, Christina; Frøkjaer, Jens Brøndum; Gregersen, Hans; Khan, Sheeba; Lelic, Dina; Lottrup, Christian; Drewes, Asbjørn Mohr

    2016-08-01

    Symptoms relating to esophageal sensory abnormalities can be encountered in the clinical environment. Such sensory abnormalities may be present in demonstrable disease, such as erosive esophagitis, and in the ostensibly normal esophagus, such as non-erosive reflux disease or functional chest pain. In this review, the authors discuss esophageal sensation and the esophageal pain system. In addition, the authors provide a primer concerning the techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of esophageal sensory function. Such technological advances, whilst not readily available in the clinic may facilitate the stratification and individualization of therapy in disorders of esophageal sensation in the future. PMID:26890720

  19. Understanding the sensory irregularities of esophageal disease.

    PubMed

    Farmer, Adam D; Brock, Christina; Frøkjaer, Jens Brøndum; Gregersen, Hans; Khan, Sheeba; Lelic, Dina; Lottrup, Christian; Drewes, Asbjørn Mohr

    2016-08-01

    Symptoms relating to esophageal sensory abnormalities can be encountered in the clinical environment. Such sensory abnormalities may be present in demonstrable disease, such as erosive esophagitis, and in the ostensibly normal esophagus, such as non-erosive reflux disease or functional chest pain. In this review, the authors discuss esophageal sensation and the esophageal pain system. In addition, the authors provide a primer concerning the techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of esophageal sensory function. Such technological advances, whilst not readily available in the clinic may facilitate the stratification and individualization of therapy in disorders of esophageal sensation in the future.

  20. Uses of esophageal function testing: dysphagia.

    PubMed

    Yazaki, Etsuro; Woodland, Philip; Sifrim, Daniel

    2014-10-01

    Esophageal function testing should be used for differential diagnosis of dysphagia. Dysphagia can be the consequence of hypermotility or hypomotility of the muscles of the esophagus. Decreased esophageal or esophagogastric junction distensibility can provoke dysphagia. The most well established esophageal dysmotility is achalasia. Other motility disorders can also cause dysphagia. High-resolution manometry (HRM) is the gold standard investigation for esophageal motility disorders. Simultaneous measurement of HRM and intraluminal impedance can be useful to assess motility and bolus transit. Impedance planimetry measures distensibility of the esophageal body and gastroesophageal junction in patients with achalasia and eosinophilic esophagitis. PMID:25216909

  1. 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.

  2. Adenocarcinoma arising in a gastrocystoplasty

    PubMed Central

    Balachandra, B; Swanson, P E; Upton, M P; Yeh, M M

    2007-01-01

    Gastrocystoplasty is a form of surgical bladder augmentation or neobladder used to restore bladder capacity and compliance in children and in patients with neurogenic bladder. Other forms of bladder augmentation include ileocystoplasty and colocystoplasty. Reported complications of gastrocystoplasty include post‐operative bleeding, haematuria, stricture, metabolic alkalosis and rupture of the gastric segment. There are reports of adenocarcinomas arising in the setting of ileocystoplasty and colocystoplasty. However, the first case of adenocarcinoma arising in the setting of a gastrocystoplasty is reported. PMID:17213351

  3. Adenocarcinoma arising in a gastrocystoplasty.

    PubMed

    Balachandra, B; Swanson, P E; Upton, M P; Yeh, M M

    2007-01-01

    Gastrocystoplasty is a form of surgical bladder augmentation or neobladder used to restore bladder capacity and compliance in children and in patients with neurogenic bladder. Other forms of bladder augmentation include ileocystoplasty and colocystoplasty. Reported complications of gastrocystoplasty include post-operative bleeding, haematuria, stricture, metabolic alkalosis and rupture of the gastric segment. There are reports of adenocarcinomas arising in the setting of ileocystoplasty and colocystoplasty. However, the first case of adenocarcinoma arising in the setting of a gastrocystoplasty is reported.

  4. 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

  5. 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.

  6. 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; Mariette, Christophe; 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.

  7. A Model for Predicting the Future Risk of Incident Erosive Esophagitis in an Asymptomatic Population Undergoing Regular Check-ups.

    PubMed

    Kang, Soo Hoon; Lim, Yaeji; Lee, Hyuk; Kim, Joungyoun; Chi, Sangah; Min, Yang Won; Min, Byung-Hoon; Lee, Jun Haeng; Son, Hee Jung; Ryu, Seungho; Rhee, Poong-Lyul; Kim, Jae J

    2016-01-01

    Erosive esophagitis is a major risk factor for Barrett esophagus and esophageal adenocarcinoma. Information regarding the putative risk factors for developing erosive esophagitis is considerably heterogeneous; thus, a risk model is required to clinically predict the incidence of erosive esophagitis. This study was to derive and validate a predictive model for the incidence of developing erosive esophagitis after negative index endoscopy in a population subjected to routine health check-ups. This retrospective cohort study of health check-ups included 11,535 patients who underwent repeated screening endoscopy after >3 years from a negative index endoscopy. We used logistic regression analysis to predict the incidence of erosive esophagitis, and a Simple Prediction of Erosive Esophagitis Development score for risk assessment was developed and internally validated using the split-sample approach. The development and validation cohorts included 5765 patients (675 with erosive esophagitis [11.7%]) and 5770 patients (670 with erosive esophagitis [11.6%]), respectively. The final model included sex, smoking behavior, body mass index, hypertension, and the triglyceride level as variables. This model predicted 667 cases of erosive esophagitis, yielding an expected-to-observed ratio of 1.00 (95% confidence interval [CI], 0.92-1.07). A simplified 5-item risk scoring system based on coefficients was developed, with a risk of erosive esophagitis of 6.2% (95% CI, 5.2-7.1) for the low-risk group (score ≤2), 15.1% (95% CI, 13.5-16.6) for the intermediate-risk group (score ≤3, 4), and 18.2% (95% CI, 15.2-21.3) for the high-risk group (score ≥5). The discriminative performance of the risk-prediction score was consistent in the derivation cohort and validation cohort (c-statistics 0.68 and 0.64, respectively); the calibration was good (Brier score 0.099 and 0.1, respectively). In conclusion, a simple risk-scoring model using putative risk factors can predict the future

  8. A Model for Predicting the Future Risk of Incident Erosive Esophagitis in an Asymptomatic Population Undergoing Regular Check-ups.

    PubMed

    Kang, Soo Hoon; Lim, Yaeji; Lee, Hyuk; Kim, Joungyoun; Chi, Sangah; Min, Yang Won; Min, Byung-Hoon; Lee, Jun Haeng; Son, Hee Jung; Ryu, Seungho; Rhee, Poong-Lyul; Kim, Jae J

    2016-01-01

    Erosive esophagitis is a major risk factor for Barrett esophagus and esophageal adenocarcinoma. Information regarding the putative risk factors for developing erosive esophagitis is considerably heterogeneous; thus, a risk model is required to clinically predict the incidence of erosive esophagitis. This study was to derive and validate a predictive model for the incidence of developing erosive esophagitis after negative index endoscopy in a population subjected to routine health check-ups. This retrospective cohort study of health check-ups included 11,535 patients who underwent repeated screening endoscopy after >3 years from a negative index endoscopy. We used logistic regression analysis to predict the incidence of erosive esophagitis, and a Simple Prediction of Erosive Esophagitis Development score for risk assessment was developed and internally validated using the split-sample approach. The development and validation cohorts included 5765 patients (675 with erosive esophagitis [11.7%]) and 5770 patients (670 with erosive esophagitis [11.6%]), respectively. The final model included sex, smoking behavior, body mass index, hypertension, and the triglyceride level as variables. This model predicted 667 cases of erosive esophagitis, yielding an expected-to-observed ratio of 1.00 (95% confidence interval [CI], 0.92-1.07). A simplified 5-item risk scoring system based on coefficients was developed, with a risk of erosive esophagitis of 6.2% (95% CI, 5.2-7.1) for the low-risk group (score ≤2), 15.1% (95% CI, 13.5-16.6) for the intermediate-risk group (score ≤3, 4), and 18.2% (95% CI, 15.2-21.3) for the high-risk group (score ≥5). The discriminative performance of the risk-prediction score was consistent in the derivation cohort and validation cohort (c-statistics 0.68 and 0.64, respectively); the calibration was good (Brier score 0.099 and 0.1, respectively). In conclusion, a simple risk-scoring model using putative risk factors can predict the future

  9. New and emerging combination therapies for esophageal cancer

    PubMed Central

    Wiedmann, Marcus W; Mössner, Joachim

    2013-01-01

    Esophageal cancer comprises two different histological forms – squamous cell carcinoma (SCC) and adenocarcinoma (AC). While the incidence of AC has increased steeply in Western countries during the last few years, the incidence of SCC is fairly stable. Both forms differ in pathogenesis and response to chemotherapy and radiation therapy. Plenty of studies have evaluated new chemotherapy combination regimens in the neoadjuvant, adjuvant, and palliative setting. In addition, new radiation and chemoradiation protocols have been investigated. Finally, molecular-targeted therapy has been included in several new randomized prospective trials. Therefore, this review presents new data on this topic and critically discusses promising approaches towards a more effective treatment in a disease with a grim prognosis. PMID:23869177

  10. Eosinophilic Esophagitis in Pediatric and Adolescent Patients

    MedlinePlus

    ... and Adolescent Patients Eosinophilic Esophagitis in Pediatric and Adolescent Patients Basics Overview Eosinophilic esophagitis also known as ( ... children may have vomiting and abdominal pain, and adolescents may complain of the feeling of food getting ...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. Prevention and Treatment of Esophageal Stenosis after Endoscopic Submucosal Dissection for Early Esophageal Cancer

    PubMed Central

    Wen, Jing; Lu, Zhongsheng; Liu, Qingsen

    2014-01-01

    Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions is associated with a risk of esophageal stenosis, especially for near-circumferential or circumferential esophageal mucosal defects. Here, we review historic and modern studies on the prevention and treatment of esophageal stenosis after ESD. These methods include prevention via pharmacological treatment, endoscopic autologous cell transplantation, endoscopic esophageal dilatation, and stent placement. This short review will focus on direct prevention and treatment, which may help guide the way forward. PMID:25386186

  16. Prediagnosis aspirin use and outcomes in a prospective cohort of esophageal cancer patients

    PubMed Central

    Araujo, James L.; Altorki, Nasser K.; Sonett, Joshua R.; Rodriguez, Adriana; Sungur-Stasik, Kivilcim; Spinelli, Cathy F.; Neugut, Alfred I.; Abrams, Julian A.

    2016-01-01

    Background: Esophageal cancer remains associated with poor outcomes, yet little is known regarding factors that influence survival. Aspirin use prior to cancer diagnosis may influence outcomes. We aimed to assess the effects of prediagnosis aspirin use in patients with esophageal cancer. Methods: We conducted a prospective cohort study of newly-diagnosed esophageal cancer patients at two tertiary care centers. We assessed history of prediagnosis aspirin use, and prospectively followed patients and assessed mortality, cause of death, and development of metastases. Results: We enrolled 130 patients, the majority of whom were male (81.5%) and had adenocarcinoma (80.8%). Overall, 57 patients (43.9%) were regular aspirin users. In unadjusted analyses, we found no difference in all-cause mortality between aspirin users and nonusers. In multivariate analyses, prediagnosis aspirin use was not associated with all-cause mortality [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.48–1.57] or esophageal cancer-specific mortality (HR 1.07, 95% CI 0.52–2.21). Prediagnosis aspirin use was associated with a significantly increased risk of interval metastasis (HR 3.59, 95% CI 1.08–11.96). Conclusions: In our cohort of esophageal cancer patients, prediagnosis aspirin use was not associated with all-cause or cancer-specific mortality. However, risk of interval metastatic disease was increased among those who took aspirin regularly prediagnosis. Future studies are warranted to assess whether aspirin influences the molecular characteristics of esophageal tumors, with potential prognostic and therapeutic implications. PMID:27803735

  17. 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

  18. Gallium-67 imaging in candidal esophagitis

    SciTech Connect

    Rundback, J.H.; Goldfarb, C.R.; Ongseng, F. )

    1990-01-01

    Ga-67 scanning has been used to evaluate esophageal carcinoma. It has demonstrated candidal infection in other body sites and, in one previous case, in the esophagus. The authors present a case of diffuse esophageal uptake of Ga-67 in esophageal candidiasis.

  19. [Combined radiotherapy and chemotherapy for the treatment of esophageal cancer].

    PubMed

    Mishina, H; Okuyama, S; Lim, I; Yamagata, R; Taima, T; Ogasawara, T; Yamamoto, K

    1983-05-01

    Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, therapeutic responses were satisfactory: seven out of 8 patients have survived for a range of 3 to 20 months and still active at work or cancer-free. However, one patient suffered from a second malignancy of adenocarcinoma of the upper esophagus different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammation), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present therapeutic design is being expanded to the treatment of cancer of other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects.

  20. New TNM staging system for esophageal cancer: what chest radiologists need to know.

    PubMed

    Hong, Su Jin; Kim, Tae Jung; Nam, Kyung Bum; Lee, In Sun; Yang, Hee Chul; Cho, Sukki; Kim, Kwhanmien; Jheon, Sanghoon; Lee, Kyung Won

    2014-10-01

    Esophageal cancer is a leading cause of cancer-related deaths worldwide, and the 5-year relative survival rate remains less than 20% in the United States. The treatment of esophageal cancer should be stage specific for better clinical outcomes. Recent treatment paradigms tend to involve a multimodality approach to management, which includes surgical resection and preoperative or definitive chemoradiation therapy. Accurate pretreatment staging of esophageal cancer is integral for assessing operability and determining a suitable treatment plan. The American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) have published the seventh edition of the staging manual for cancer in the esophagus and esophagogastric junction. Unlike the sixth edition, the revised staging manual is data driven and harmonized with the staging of stomach cancer. Improvements include new definitions for the anatomic classifications Tis, T4, regional lymph node, N, and M and the addition of nonanatomic cancer characteristics (histopathologic cell type, histologic grade, and cancer location). Given the recent increase in the incidence of adenocarcinoma of the distal esophagus, esophagogastric junction, and gastric cardia, the staging of tumors in the esophagogastric junction has been addressed. Radiologists must understand the details of the seventh edition of the AJCC-UICC staging system for esophageal cancer and use appropriate imaging modalities, such as computed tomography (CT), endoscopic ultrasonography, and positron emission tomography/CT, for initial staging.

  1. Photodynamic therapy (PDT) with endoscopic ultrasound for the treatment of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Woodward, Timothy A.; Wolfsen, Herbert C.

    2000-05-01

    In 1995, PDT was approved for palliative use in patients with esophageal cancer. We report our experience using PDT to treat esophageal cancer patients previously treated with combination chemotherapy and radiation therapy. In our series, nine patients referred for PDT with persistent esophageal cancer after chemo-radiation therapy. We found: (1) All patients were men with a mean age of 63 years and eight out of nine had adenocarcinoma with Barrett's esophagus; (2) All patients required endoscopic dilation after PDT; (3) At a mean follow up of 4 months, two T2N0 patients had no demonstrable tumor and all three T3N0 patients had greater than 50% tumor reduction (the partially responsive T3N0 patients will be offered repeat PDT); (4) Patients with metastatic disease (T3N1 or M1) had effective dysphagia palliation. Thus, PDT is safe and effective in ablating all or most tumor in patients with persistent esophageal cancer after chemotherapy and radiation therapy.

  2. The Effect of Neoadjuvant Therapy on Early Complications of Esophageal Cancer Surgery

    PubMed Central

    Rajabi Mashhadi, Mohammadtaghi; Bagheri, Reza; Abdollahi, Abbas; Ghamari, Mohammad Javad; Shahidsales, Soudabeh; Salehi, Maryam; Shahkaram, Reza; Majidi, Mohamad Reza; Sheibani, Shima

    2015-01-01

    Introduction: Early diagnosis and appropriate treatment is required in esophageal cancer due to its invasive nature. The aim of this study was to evaluate early post-esophagectomy complications in patients with esophageal cancer who received neoadjuvant chemoradiotherapy (NACR). Materials and Methods: This randomized clinical trial was carried out between 2009 and 2011. Patients with lower-third esophageal cancer were randomly assigned to one of two groups. The first group consisted of 50 patients receiving standard chemoradiotherapy (Group A) and then undergoing surgery, and the second group consisted of 50 patients undergoing surgery only (Group B). Patients were evaluated with respect to age, gender, clinical symptoms, type of pathology, time of surgery, perioperative blood loss, and number of lymph nodes resected as well as early post-operative complicate including leakage at the anastomosis site, chylothorax and pulmonary complications, hospitalization period, and mortality rate within the first 30 days after surgery. Results: The mean age of patients was 55 years. Seventy-two patients had squamous cell carcinoma (SCC) and 28 patients had adenocarcinoma (ACC). There was no significant difference between the two groups with respect to age, gender, time of surgery, complications including anastomotic leakage, chylothorax, pulmonary complications, cardiac complications, deep venous thrombosis (DVT), or mortality. However, there was a significant difference between the two groups regarding hospital stay, time of surgery, perioperative blood loss, and number of lymph nodes resected. Conclusion: The use of NACR did not increase early post-operative complications or mortality among patients with esophageal cancer. PMID:26788476

  3. Outcomes of esophageal surgery, especially of the lower esophageal sphincter.

    PubMed

    Bonavina, Luigi; Siboni, Stefano; Saino, Greta I; Cavadas, Demetrio; Braghetto, Italo; Csendes, Attila; Korn, Owen; Figueredo, Edgar J; Swanstrom, Lee L; Wassenaar, Eelco

    2013-10-01

    This paper includes commentaries on outcomes of esophageal surgery, including the mechanisms by which fundoduplication improves lower esophageal sphincter (LES) pressure; the efficacy of the Linx™ management system in improving LES function; the utility of radiologic characterization of antireflux valves following surgery; the correlation between endoscopic findings and reported symptoms following antireflux surgery; the links between laparoscopic sleeve gastrectomy and decreased LES pressure, endoscopic esophagitis, and gastroesophageal reflux disease (GERD); the less favorable outcomes following fundoduplication among obese patients; the application of bioprosthetic meshes to reinforce hiatal repair and decrease the incidence of paraesophageal hernia; the efficacy of endoluminal antireflux procedures, and the limited efficacy of revisional antireflux operations, underscoring the importance of good primary surgery and diligent work-up to prevent the necessity of revisional procedures. PMID:24117632

  4. ESOPHAGEAL ATRESIA WITH RECURRENT TRACHEOESOPHAGEAL FISTULAS AND MICRODUPLICATION 22q11.23.

    PubMed

    Puvabanditsin, S; Garrow, E; February, M; Yen, E; Mehta, R

    2015-01-01

    The microduplication 22q11.2 syndrome has a wide range of clinical manifestations. The phenotype ranges from normal to mental retardation and congenital anomalies. Esophageal atresia/tracheoesophageal fistula (EA/TEF) has recently been linked with the Tbx1 gene mutation located on the long arm of chromosome 22(22q11.21). We report a case with 1.4 Mb 22q11.23 duplication detected by array-CGH. The father of this infant has the same interstitial microduplication but with a normal phenotype. The phenotype seen in our case is type C (3B) esophageal atresia, tracheoesophageal fistula, and ventricular septal defect. Our patient underwent primary repair of OA/TEF malformations, which was later complicated by pneumonia and a recurrent TEF. PMID:26625662

  5. Eosinophilic esophagitis in an octogenarian

    PubMed Central

    Trifan, Anca; Stoica, Oana; Chihaia, Catalin-Alexandru; Danciu, Mihai; Stanciu, Carol; Singeap, Ana-Maria

    2016-01-01

    Abstract Introduction: Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized clinically by symptoms related to esophageal dysfunction and histologically by a marked eosinophilic infiltrate in the esophageal mucosa. What was once considered a rare disease has nowadays become one of the most frequent esophageal diseases in the Western countries, occupying a place just next to the gastroesophageal reflux disease. EoE etiology and pathogenesis remain largely unknown, although most studies consider that allergic and genetic factors play the most important role. Methods: We report the case of EoE in an elderly male (octogenarian), giving a brief review of the current data related to epidemiology, pathogenesis, diagnosis, and treatment of the disease. Results: Dysphagia to solid foods was the leading symptom, and endoscopic findings included white exudates, longitudinal furrows, and concentric mucosal rings, all suggestive for EoE. Diagnosis relied on histological findings in esophageal mucosal biopsies (>30 eosinophils per high power field). He was treated with topical steroids for 8 weeks, symptoms improved gradually and the patient remained in remission at the 8-month follow-up. Conclusion: This case emphasizes that EoE may occur in very old patients and gastroenterologists should have a high index of suspicion of this disorder in any elderly with dysphagia and endoscopic relevant features. PMID:27741150

  6. 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

  7. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true EA components. 651.34 Section 651.34 National 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...

  8. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 4 2012-07-01 2011-07-01 true EA components. 651.34 Section 651.34 National 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...

  9. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 4 2014-07-01 2013-07-01 true EA components. 651.34 Section 651.34 National 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...

  10. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 4 2013-07-01 2013-07-01 false EA components. 651.34 Section 651.34 National 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...

  11. 32 CFR 651.34 - EA components.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false EA components. 651.34 Section 651.34 National 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...

  12. Incidence of Microscopically Positive Proximal Margins in Adenocarcinoma of the Gastroesophageal Junction

    PubMed Central

    Wang, Gang; Zhang, Zhihong; Shen, Lizong

    2014-01-01

    Aim To investigate the incidence and risk factors of microscopically positive proximal margins in Chinese patients with adenocarcinoma of the gastroesophageal junction. Methods The medical records of 483 patients, who underwent surgical treatment with curative intent for adenocarcinoma of the gastroesophageal junction in a single high-volume tertiary medical center, were reviewed. Demographic, radiographic, endoscopic, pathologic, and treatment-related variables were evaluated. All proximal margins were re-evaluated by two experienced pathologists, and a positive proximal margin was defined as the microscopic presence of invasive tumor cells seen at the esophageal transaction margin submitted en face on final paraffin sections. Results The incidence of positive proximal margins was 23.81% in this series. Siewert type, depth of tumor invasion, lymph node involvement, presence of vascular or lymphatic invasion, and presence of perineural invasion were significantly associated with positive proximal margins. On multivariate analysis, the presence of vascular or lymphatic invasion and advanced-stage disease were independent risk factors for positive proximal margins in patients with adenocarcinoma of the gastroesophageal junction. Conclusion Residual cancer at proximal resection margins remains a major issue for the surgical treatment of adenocarcinoma of the gastroesophageal junction in China. PMID:24505353

  13. [Caustic esophagitis: surgical management].

    PubMed

    Huamán, M; Santibáñez, G; Ayala, L; Jáuregui, F; Madalengoitia, G

    1990-01-01

    The authors present 28 report cases of severe caustic esophagitis who underwent surgery at the Hospital Nacional Edgardo Rebagliati Martins I.P.S.S., from 1987 to February 1991. All were treated by esophagocoloplasty and when the proximal cervical esophagus was injured, by pharingocoloplasty. Eighteen patients (64.28%) were female and 10 (35.72%) male. Whose ages ranged between 15 and 75 years with an average of 34 years. Ten patients (36%) suffered pharingocoloplasty and in the remaining 18 (64%) a esophagocoloplasty (esophagogastric colonic interposition) was made. Postoperative morbidity corresponded in 5 cases (18%) to respiratory Infections, in 3 cases (11%) pneumothorax, in 2 cases (7%) pleural effusions and only one case presented a small cervical leak. All of them were satisfactory solved by conservatory medical treatment. Only two cases (7%) with late postoperative stenosis required reintervention and a simple cervical plasty was made. There were no complications as mediastinitis, necrosis of the colon graft hemorrhage. Operatory mortality was 0% and the long term follow up of all patients is satisfactory, having our first report cases more than 4 years of postoperative follow up.

  14. 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

  15. Gastric adenocarcinoma with prostatic metastasis.

    PubMed

    Roshni, S; Anoop, Tm; Preethi, Tr; Shubanshu, G; Lijeesh, Al

    2014-06-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  16. Gastric Adenocarcinoma with Prostatic Metastasis

    PubMed Central

    Roshni, S; Preethi, TR; Shubanshu, G; Lijeesh, AL

    2014-01-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  17. Hyperthermochemoradiotherapy for esophageal cancer (review).

    PubMed

    Maehara, Y; Kuwano, H; Kitamura, K; Matsuda, H; Sugimachi, K

    1992-01-01

    Hyperthermia is effective for the treatment of cancer when applied concomitantly with chemotherapy and irradiation. However, it is difficult to heat deep portions of the body including the esophagus. Cancer of the esophagus still poses considerable treatment problems, with a poor 5-year survival rate after surgery, an even worse outlook after radiation and surgery, and a not very satisfactory response to chemotherapy. We, therefore, devised an electrode for radio frequency, and we have been successfully using this electrode in the treatment of esophageal cancer. The 5-year survival rates of patients with esophageal cancer, given either preoperative hyperthermochemoradiotherapy or chemoradiotherapy, were 43.2 and 14.7%, respectively. Immediate improvement of subjective complaints and decrease or elimination of the cancer lesion are so distinct that this treatment, by means of an endotract antenna, shows promise as a modality for esophageal lesions.

  18. Surgical treatments for esophageal cancers

    PubMed Central

    Allum, William H.; Bonavina, Luigi; Cassivi, Stephen D.; Cuesta, Miguel A.; Dong, Zhao Ming; Felix, Valter Nilton; Figueredo, Edgar; Gatenby, Piers A.C.; Haverkamp, Leonie; Ibraev, Maksat A.; Krasna, Mark J.; Lambert, René; Langer, Rupert; Lewis, Michael P.N.; Nason, Katie S.; Parry, Kevin; Preston, Shaun R.; Ruurda, Jelle P.; Schaheen, Lara W.; Tatum, Roger P.; Turkin, Igor N.; van der Horst, Sylvia; van der Peet, Donald L.; van der Sluis, Peter C.; van Hillegersberg, Richard; Wormald, Justin C.R.; Wu, Peter C.; Zonderhuis, Barbara M.

    2015-01-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high-grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long-term quality of life in patients following esophagectomy. PMID:25266029

  19. 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.

  20. Prevalence of Eosinophilic Esophagitis and Lymphocytic Esophagitis in Adults with Esophageal Food Bolus Impaction.

    PubMed

    Truskaite, Kotryna; Dlugosz, Aldona

    2016-01-01

    Background. The relation of esophageal food bolus impaction (FBI) to eosinophilic esophagitis (EoE) and lymphocytic esophagitis (LyE) is unclear. The aim of this study was to determine the prevalence of EoE and LyE among adults with FBI. Methods. In this retrospective study we analyzed data from all patients referred for gastroscopy during the past 5 years, because of a present or recent episode of FBI. Results. We found 238 patients with FBI (median age 51 (17-96), 71% males). Endoscopic therapy was required in 143 patients. Esophageal biopsies were obtained in 185 (78%) patients. All biopsies were assessed for numbers of eosinophils and lymphocytes. EoE was found in 18% of patients who underwent biopsy. We found 41 patients (22%) who fulfilled the criteria for both EoE and LyE (EoE/LyE). LyE was found in the 9% of patients with FBI. EoE together with EoE/LyE was the leading cause of FBI in patients ≤50 years (64%). GERD was the leading cause of FBI among patients older than 50 years (42%). Conclusions. Our study showed that EoE was the leading cause of FBI in particular among young adults. Our study highlights the need for esophageal biopsies in any patient with FBI.

  1. Prevalence of Eosinophilic Esophagitis and Lymphocytic Esophagitis in Adults with Esophageal Food Bolus Impaction

    PubMed Central

    Truskaite, Kotryna

    2016-01-01

    Background. The relation of esophageal food bolus impaction (FBI) to eosinophilic esophagitis (EoE) and lymphocytic esophagitis (LyE) is unclear. The aim of this study was to determine the prevalence of EoE and LyE among adults with FBI. Methods. In this retrospective study we analyzed data from all patients referred for gastroscopy during the past 5 years, because of a present or recent episode of FBI. Results. We found 238 patients with FBI (median age 51 (17–96), 71% males). Endoscopic therapy was required in 143 patients. Esophageal biopsies were obtained in 185 (78%) patients. All biopsies were assessed for numbers of eosinophils and lymphocytes. EoE was found in 18% of patients who underwent biopsy. We found 41 patients (22%) who fulfilled the criteria for both EoE and LyE (EoE/LyE). LyE was found in the 9% of patients with FBI. EoE together with EoE/LyE was the leading cause of FBI in patients ≤50 years (64%). GERD was the leading cause of FBI among patients older than 50 years (42%). Conclusions. Our study showed that EoE was the leading cause of FBI in particular among young adults. Our study highlights the need for esophageal biopsies in any patient with FBI. PMID:27547221

  2. Prevalence of Eosinophilic Esophagitis and Lymphocytic Esophagitis in Adults with Esophageal Food Bolus Impaction.

    PubMed

    Truskaite, Kotryna; Dlugosz, Aldona

    2016-01-01

    Background. The relation of esophageal food bolus impaction (FBI) to eosinophilic esophagitis (EoE) and lymphocytic esophagitis (LyE) is unclear. The aim of this study was to determine the prevalence of EoE and LyE among adults with FBI. Methods. In this retrospective study we analyzed data from all patients referred for gastroscopy during the past 5 years, because of a present or recent episode of FBI. Results. We found 238 patients with FBI (median age 51 (17-96), 71% males). Endoscopic therapy was required in 143 patients. Esophageal biopsies were obtained in 185 (78%) patients. All biopsies were assessed for numbers of eosinophils and lymphocytes. EoE was found in 18% of patients who underwent biopsy. We found 41 patients (22%) who fulfilled the criteria for both EoE and LyE (EoE/LyE). LyE was found in the 9% of patients with FBI. EoE together with EoE/LyE was the leading cause of FBI in patients ≤50 years (64%). GERD was the leading cause of FBI among patients older than 50 years (42%). Conclusions. Our study showed that EoE was the leading cause of FBI in particular among young adults. Our study highlights the need for esophageal biopsies in any patient with FBI. PMID:27547221

  3. Variety in vegetable and fruit consumption and the risk of gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Jeurnink, S M; Büchner, F L; Bueno-de-Mesquita, H B; Siersema, P D; Boshuizen, H C; Numans, M E; Dahm, C C; Overvad, K; Tjønneland, A; Roswall, N; Clavel-Chapelon, F; Boutron-Ruault, M C; Morois, S; Kaaks, R; Teucher, B; Boeing, H; Buijsse, B; Trichopoulou, A; Benetou, V; Zylis, D; Palli, D; Sieri, S; Vineis, P; Tumino, R; Panico, S; Ocké, M C; Peeters, P H M; Skeie, G; Brustad, M; Lund, E; Sánchez-Cantalejo, E; Navarro, C; Amiano, P; Ardanaz, E; Ramón Quirós, J; Hallmans, G; Johansson, I; Lindkvist, B; Regnér, S; Khaw, K T; Wareham, N; Key, T J; Slimani, N; Norat, T; Vergnaud, A C; Romaguera, D; Gonzalez, C A

    2012-09-15

    Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow-up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow-up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79-0.97 and 0.76; 95% CI 0.62-0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded.

  4. 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.

  5. Imaging and Clinicopathologic Features of Esophageal Gastrointestinal Stromal Tumors

    PubMed Central

    Winant, Abbey J.; Gollub, Marc J.; Shia, Jinru; Antonescu, Christina; Bains, Manjit S.; Levine, Marc S.

    2016-01-01

    OBJECTIVE The purpose of this article is to describe the imaging and clinicopathologic characteristics of esophageal gastrointestinal stromal tumors (GISTs) and to emphasize the features that differentiate esophageal GISTs from esophageal leiomyomas. MATERIALS AND METHODS A pathology database search identified all surgically resected or biopsied esophageal GISTs, esophageal leiomyomas, and esophageal leiomyosarcomas from 1994 to 2012. Esophageal GISTs were included only if imaging studies (including CT, fluoroscopic, or 18F-FDG PET/CT scans) and clinical data were available. RESULTS Nineteen esophageal mesenchymal tumors were identified, including eight esophageal GISTs (42%), 10 esophageal leiomyomas (53%), and one esophageal leiomyosarcoma (5%). Four patients (50%) with esophageal GIST had symptoms, including dysphagia in three (38%), cough in one (13%), and chest pain in one (13%). One esophageal GIST appeared on barium study as a smooth submucosal mass. All esophageal GISTs appeared on CT as well-marginated predominantly distal lesions, isoattenuating to muscle, that moderately enhanced after IV contrast agent administration. Compared with esophageal leiomyomas, esophageal GISTs tended to be more distal, larger, and more heterogeneous and showed greater IV enhancement on CT. All esophageal GISTs showed marked avidity (mean maximum standardized uptake value, 16) on PET scans. All esophageal GISTs were positive for c-KIT (a cell-surface transmembrane tyrosine kinase also known as CD117) and CD34. On histopathology, six esophageal GISTs (75%) were of the spindle pattern and two (25%) were of a mixed spindle and epithelioid pattern. Five esophageal GISTs had exon 11 mutations (with imatinib sensitivity). Clinical outcome correlated with treatment strategy (resection plus adjuvant therapy or resection alone) rather than risk stratification. CONCLUSION Esophageal GISTs are unusual but clinically important mesenchymal neoplasms. Although esophageal GISTs and

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

    PubMed

    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

    2014-09-01

    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.

  7. [Endolymphatic sac adenocarcinoma: case report].

    PubMed

    Silveira, Roberto Leal; Gusmão, Sebastião Silva; Pittella, José Eymard H; Santos, Sinval Pereira

    2002-09-01

    A case of endolymphatic sac adenocarcinoma is reported and the literature is reviewed. The clinical picture was presented by vertigo and progressive hearing loss caused by a tumor of the endolymphatic sac. The surgical removal was complete, via a retro and translabyrinthine approach. Endolymphatic sac tumors are locally invasive, involve the petrous bone and the mastoid. The radical surgery presents good outcome.

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

    ClinicalTrials.gov

    2016-07-30

    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

  9. Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    PubMed

    Chen, Yao-Tseng; Panarelli, Nicole C; Piotti, Kathryn C; Yantiss, Rhonda K

    2014-05-01

    Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

  10. 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

  11. Esophageal manifestations of celiac disease.

    PubMed

    Lucendo, A J

    2011-09-01

    Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated.

  12. 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.

  13. 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

  14. Obesity and outcomes in patients treated with chemoradiotherapy for esophageal carcinoma.

    PubMed

    Wang, J; Myles, B; Wei, C; Chang, J Y; Hofstetter, W L; Ajani, J A; Swisher, S G; Cox, J D; Komaki, R; Liao, Z; Lin, S H

    2014-01-01

    Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. It was hypothesized that obesity status affects disease outcomes and treatment-related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). From March 2002 to April 2010, 405 patients with non-metastatic esophageal carcinoma at MD Anderson Cancer Center treated with either definitive or neoadjuvant CRT were retrospectively analyzed. Patients were categorized as either obese (BMI ≥ 25 kg/m(2) ) or nonobese (BMI < 25 kg/m(2) ). Progression-free survival and overall survival times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. One hundred fifteen (28.4%) patients were classified as nonobese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (P < 0.001), adenocarcinoma located distally (P < 0.001), and have undergone surgery (P = 0.004). Obesity was not associated with either worse operative morbidity/mortality (P > 0.05) or worse positron emission tomography tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (P = 0.98) on multivariate analysis. There was also no difference in overall survival, locoregional control, or metastasis-free survival between obese and nonobese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation-induced high-grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high-grade hematologic toxicity (P < 0.001). In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, data suggest it may be associated with decreased risk of acute chemotherapy- and radiotherapy-related treatment toxicities.

  15. Obesity and Outcomes in Patients Treated with Chemoradiotherapy for Esophageal Carcinoma

    PubMed Central

    Wang, Jingya; Myles, Bevan; Wei, Caimiao; Chang, Joe Y.; Hofstetter, Wayne L.; Ajani, Jaffer A.; Swisher, Stephen G.; Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing; Lin, Steven H.

    2013-01-01

    Background Body mass index (BMI) is a risk factor for comorbid illnesses and cancer development. We hypothesized that obesity status affects disease outcomes and treatment-related toxicities in esophageal cancer patients treated with chemoradiotherapy (CRT). Methods From March 2002 to April 2010, we retrospectively analyzed 405 patients with non-metastatic esophageal carcinoma at MD Anderson Cancer Center, treated with either definitive or neoadjuvant CRT. Patients were categorized as either obese (BMI ≥ 25 kg/m2) or non-obese (BMI < 25 kg/m2). Progression-free survival (PFS) and overall survival (OS) times were examined using the Kaplan-Meier method and Cox proportional hazards regression analysis. Results One hundred fifteen (28.4%) patients were classified as non-obese and 290 (71.6%) as obese. Obese patients were more likely than others to have several comorbid diseases (p < 0.001), adenocarcinoma located distally (p < 0.001), and have undergone surgery (p = 0.004). Obesity was not associated with either worse operative morbidity/mortality (p > 0.05) or worse positron emission tomography (PET) tumor response (P = 0.46) on univariate analysis, nor with worse pathologic complete response (pCR) (P = 0.98) on multivariate analysis. There was also no difference in OS, locoregional control, or metastasis-free survival between obese and non-obese patients (P = 0.86). However, higher BMI was associated with reduced risk of chemoradiation-induced high-grade esophagitis (P = 0.021), esophageal stricture (P < 0.001), and high-grade hematologic toxicity (P < 0.001). Conclusions In esophageal cancer patients treated with CRT, obesity is not predictive of poorer disease outcomes or operative morbidities; instead, our data suggest it may be associated with decreased risk of acute chemotherapy and radiotherapy-related treatment toxicities. PMID:23621168

  16. 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

  17. 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

  18. Esophageal wall blood perfusion during contraction and transient lower esophageal sphincter relaxation in humans

    PubMed Central

    Jiang, Yanfen; Bhargava, Valmik; Kim, Young Sun

    2012-01-01

    We recently reported that esophageal contraction reduces esophageal wall perfusion in an animal study. Our aim was to determine esophageal wall blood perfusion (EWBP) during esophageal contraction and transient lower esophageal sphincter relaxations (TLESRs) in humans. We studied 12 healthy volunteers. A custom-designed laser Doppler probe was anchored to the esophageal wall, 4–6 cm above the LES, by use of the Bravo pH system so that the laser light beam stay directed toward the esophageal mucosa. A high-resolution manometry equipped with impedance electrodes recorded esophageal pressures and reflux events. Synchronized pressure, impedance, pH, and EWBP recordings were obtained during dry and wet swallows and following a meal. Stable recordings of laser Doppler EWBP were only recorded when the laser Doppler probe was firmly anchored to the esophageal wall. Esophageal contractions induced by dry and wet swallows resulted in 46 ± 9% and 60 ± 10% reduction in the EWBP, respectively (compared to baseline). Reduction in EWBP was directly related to the amplitude (curvilinear fit) and duration of esophageal contraction. Atropine reduced the esophageal contraction amplitude and decreased the EWBP reduction associated with esophageal contraction. TLESRs were also associated with reduction in the EWBP, albeit of smaller amplitude (29 ± 3%) but longer duration (19 ± 2 s) compared with swallow-induced esophageal contractions. We report 1) an innovative technique to record EWBP for extended time periods in humans and 2) contraction of circular and longitudinal muscle during peristalsis and selective longitudinal muscle contraction during TLESR causes reduction in the EWBP; 3) using our innovative technique, future studies may determine whether esophageal wall ischemia is the cause of esophageal pain/heartburn. PMID:22790599

  19. Upregulation of MALAT-1 and its association with survival rate and the effect on cell cycle and migration in patients with esophageal squamous cell carcinoma.

    PubMed

    Yao, Wenjian; Bai, Yu; Li, Yan; Guo, Ling; Zeng, Ping; Wang, Yonglian; Qi, Bo; Liu, Shangguo; Qin, Xiuguang; Li, Yongzhen; Zhao, Baosheng

    2016-04-01

    The aim of this study is to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) can be used as a potential therapy target for human esophageal squamous cell carcinoma. MALAT-1 expression levels were detected in 137 paired EC samples and adjacent nonneoplastic tissues. Human esophageal carcinoma cell lines EC9706 and KYSE150 were transfected with MALAT-1 small interference RNA. Cell proliferation, migration/invasion ability, cell cycle, and apoptosis were assessed. MALAT-1 expressed higher levels in esophageal cancer tissues when compared with paired adjacent normal tissues. This high expression was associated with a decreased survival rate. MALAT-1 knockdown induced a decrease in proliferation-enhanced apoptosis, inhibited migration/invasion, and reduced colony formation and led to cell cycle arrest at the G2/M phase. These data indicates that MALAT-1 could be exploited for therapeutic benefit.

  20. Hepatoid Adenocarcinoma of the Urachus

    PubMed Central

    Jimenez, Carlos Andrés; Carrascal, Edwin

    2016-01-01

    Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI) reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP) and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis. PMID:27803830

  1. Pradaxa-induced esophageal ulcer.

    PubMed

    Wood, Michele; Shaw, Paul

    2015-10-09

    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.

  2. 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

  3. Distal esophageal spasm: an update.

    PubMed

    Achem, Sami R; Gerson, Lauren B

    2013-09-01

    Distal esophageal spasm (DES) is an esophageal motility disorder that presents clinically with chest pain and/or dysphagia and is defined manometrically as simultaneous contractions in the distal (smooth muscle) esophagus in ≥20% of wet swallows (and amplitude contraction of ≥30 mmHg) alternating with normal peristalsis. With the introduction of high resolution esophageal pressure topography (EPT) in 2000, the definition of DES was modified. The Chicago classification proposed that the defining criteria for DES using EPT should be the presence of at least two premature contractions (distal latency<4.5 s) in a context of normal EGJ relaxation. The etiology of DES remains insufficiently understood, but evidence links nitric oxide (NO) deficiency as a culprit resulting in a disordered neural inhibition. GERD frequently coexists in DES, and its role in the pathogenesis of symptoms needs further evaluation. There is some evidence from small series that DES can progress to achalasia. Treatment remains challenging due in part to lack of randomized placebo-controlled trials. Current treatment agents include nitrates (both short and long acting), calcium-channel blockers, anticholinergic agents, 5-phosphodiesterase inhibitors, visceral analgesics (tricyclic agents or SSRI), and esophageal dilation. Acid suppression therapy is frequently used, but clinical outcome trials to support this approach are not available. Injection of botulinum toxin in the distal esophagus may be effective, but further data regarding the development of post-injection gastroesophageal reflux need to be assessed. Heller myotomy combined with fundoplication remains an alternative for the rare refractory patient. Preliminary studies suggest that the newly developed endoscopic technique of per oral endoscopic myotomy (POEM) may also be an alternative treatment modality. PMID:23892829

  4. Acute Esophageal Necrosis: An Update

    PubMed Central

    Inayat, Faisal; Hurairah, Abu; Virk, Hafeez Ul Hassan

    2016-01-01

    Acute esophageal necrosis (AEN) or “black esophagus” is a rare clinical entity with an unclear etiology. It is diagnosed at upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. The treatment is primarily medical, but the prognosis is generally poor due to advanced age and comorbid illnesses in patients who develop AEN. Herein, we discussed the implications of poor glycemic control in regards with AEN and undertook a literature review of this rare diagnosis. PMID:27583242

  5. Acute Esophageal Necrosis: An Update.

    PubMed

    Inayat, Faisal; Hurairah, Abu; Virk, Hafeez Ul Hassan

    2016-07-01

    Acute esophageal necrosis (AEN) or "black esophagus" is a rare clinical entity with an unclear etiology. It is diagnosed at upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. The treatment is primarily medical, but the prognosis is generally poor due to advanced age and comorbid illnesses in patients who develop AEN. Herein, we discussed the implications of poor glycemic control in regards with AEN and undertook a literature review of this rare diagnosis. PMID:27583242

  6. ["Esophageal" angina and angina pectoris].

    PubMed

    Bortolotti, M; Labriola, E; Sarti, P; Brunelli, F; Mazza, M; Barbara, L

    1991-04-15

    In the last few years the non cardiac angina-like chest pain has encompassed more and more agitation not only in many patients but also in cardiologists, gastroenterologists and psychologists, as it involves socio-economic, pathophysiologic and therapeutic problems. The socio-economic aspect is well explained by the fact that in the USA at least 200,000 patients a year suffering from non cardiac angina-like chest pain, even when coronary arteriography has demonstrated normal coronary vessels, nevertheless continue to require cardiologic examinations and, if no one has clearly demonstrated the origin of their pain, they continue to live as invalids in constant fear of myocardial infarction. The discovery that the esophagus may be one of the causes of chest pain in these patients presenting with a previous diagnosis of "atypical" angina pectoris, unfortunately cannot resolve definitively the problem. An association of esophageal angina in patients with angina pectoris treated for long periods of time with Ca-antagonists and nitroderivatives has been described. In addition, the provocative or spontaneous tests to demonstrate the esophageal origin of chest pain give only a "likely" and not a "definite" diagnosis of esophageal angina. This also means to no "gold standard" text exist. Lastly, the "likely" diagnosis of esophageal angina is made in only about 50% of patients leaving the problem of the remaining 50% unanswered. These uncertainties induce some psychologists to assert that the cause of non cardiac angina-like chest pain is in the head ("panic disorder") and not in the esophagus, where the observed motor disorders should be an epiphenomenon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2067672

  7. [Esophageal cancer: surgical strategies].

    PubMed

    Costa, Paulo; Esteves, Rui; Lages, Patrícia; Ferreira, Filipa

    2014-01-01

    Introdução: A ressecção transmediastínica e a ressecção transtorácica têm mortalidade hospitalar (1,4% -14%) e sobrevivência (± 25% aos cinco anos) semelhantes. A terapêutica neo-adjuvante é opção em estádios avançados. A intenção deste trabalho é apresentar uma série consecutiva de 52 doentes - opção operatória baseada na localização anatómica: tumores infra-carinais e cervicais submetidos a ressecção transmediastínica e restantes ressecções transtorácicas.Material e Métodos: O estudo incluiu 52 doentes consecutivos, sete mulheres e 45 homens, mediana de idade: 64 anos [46- 85]. Localização: cervical – um; montante da carina - 22; jusante da carina -19; cárdia tipo I –10. Histologia: 19 adenocarcinomas, 32 carcinomas pavimento-celulares, um linfoma. Vinte doentes (40%) - terapêutica neoadjuvante. Abordagem tóraco-abdominal – três, tóraco-abdómino-cervical – 20, transhiatal – 27, toracotomia exploradora – dois. Transposição gástrica 49 (anastomose cervical – 46; torácica - três); esofagocoloplastia cervical - um.Resultados: Estadiamento patológico: regressão completa - 8; Ib – 3; IIa – 9; IIb - 4; IIa – 11; IIIb -2; IIIc – 10; IV – 1; linfoma - um; não classificáveis – três. Complicações major: 37%. Ressecabilidade: 96% (50/52). Mortalidade: quatro semanas - 6%; hospitalar - 14%. Sobrevida mediana 18 meses [3-80]. Curvas de sobrevida (Kaplan-Meier): dois anos - 47%; cinco anos - 19%.Discussão: Não tendo sido demonstrada vantagem oncológica para a ressecção transtorácica ou a ressecção transmediastínica,basear a opção operatória na localização do tumor permitiu-nos com segurança e eficácia, planear e executar as ressecções esofágicas desta série.Conclusão: As curvas de sobrevida foram sobreponíveis para ressecção transtorácica e ressecção transmediastínica e bastantefavoráveis numa população com 52 % de estádios p

  8. Novel device to sample the esophageal microbiome--the esophageal string test.

    PubMed

    Fillon, Sophie A; Harris, J Kirk; Wagner, Brandie D; Kelly, Caleb J; Stevens, Mark J; Moore, Wendy; Fang, Rui; Schroeder, Shauna; Masterson, Joanne C; Robertson, Charles E; Pace, Norman R; Ackerman, Steven J; Furuta, Glenn T

    2012-01-01

    A growing number of studies implicate the microbiome in the pathogenesis of intestinal inflammation. Previous work has shown that adults with esophagitis related to gastroesophageal reflux disease have altered esophageal microbiota compared to those who do not have esophagitis. In these studies, sampling of the esophageal microbiome was accomplished by isolating DNA from esophageal biopsies obtained at the time of upper endoscopy. The aim of the current study was to identify the esophageal microbiome in pediatric individuals with normal esophageal mucosa using a minimally invasive, capsule-based string technology, the Enterotest™. We used the proximal segment of the Enterotest string to sample the esophagus, and term this the "Esophageal String Test" (EST). We hypothesized that the less invasive EST would capture mucosal adherent bacteria present in the esophagus in a similar fashion as mucosal biopsy. EST samples and mucosal biopsies were collected from children with no esophageal inflammation (n = 15) and their microbiome composition determined by 16S rRNA gene sequencing. Microbiota from esophageal biopsies and ESTs produced nearly identical profiles of bacterial genera and were different from the bacterial contents of samples collected from the nasal and oral cavity. We conclude that the minimally invasive EST can serve as a useful device for study of the esophageal microbiome. PMID:22957025

  9. Pharmacologic influence on esophageal varices

    SciTech Connect

    Lunderquist, A.; Owman, T.; Alwmark, A.; Gullstrand, P.; Hall-Angeras, M.; Joelsson, B.; Tranberg, K.G.; Pettersson, K.I.

    1983-06-01

    Selective catherization of the left gastric vein was performed after percutaneous transhepatic portography (PTP) in patients with portal hypertension and esophageal varices. Following the hypothesis that drugs increasing the lower esophageal sphincter (LES) pressure may obstruct the variceal blood flow throught the lower esophagus, the effect of different drugs (i.e., intravenous injection of vasopressin, pentagastrin, domperidone and somatostatin and subcutaneous injection of metacholine) on the variceal blood flow was examined. Vasopressin did not change the variceal blood flow; pentagastrine, with its known effect of increasing the LES pressure produced a total interruption of the flow in four of eight patients; domperiodone, also known to increase the LES pressure obstructed the variceal blood flow in the only patient examined with this drug; somatostatin has no reported action on the LES but blocked the flow in one of two patients; and metacholine, reported to increase the LES pressure did not produce any change in the flow in the three patients examined. LES pressure was recorded before and during vasopressin infusion in seven patients with portal hypertension and esophageal varices. No reaction on the pressure was found. The patient number in the study is small and the results are nonuniform but still they suggest that drugs increasing the LES tonus might be useful to control variceal blood flow.

  10. 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.

  11. Risk of adenocarcinomas of the oesophagus and gastric cardia in patients hospitalized for asthma

    PubMed Central

    Ye, W; Chow, W-H; Lagergren, J; Boffetta, P; Boman, G; Adami, H-O; Nyrén, O

    2001-01-01

    In the first cohort study of the question we followed 92 986 (42 663 men and 50 323 women) adult patients hospitalized for asthma in Sweden from 1965 to 1994 for an average of 8.5 years to evaluate their risk of oesophageal and gastric cardia adenocarcinoma. Standardized incidence ratio (SIR) adjusted for gender, age and calendar year was used to estimate relative risk, using the Swedish nationwide cancer incidence rates as reference. Asthmatic patients overall had a moderately elevated risk for oesophageal adenocarcinoma (SIR = 1.5, 95% confidence interval CI, 0.9–2.5) and gastric cardia cancer (SIR = 1.4, 95% CI, 1.0–1.9). However, the excess risks were largely confined to asthmatic patients who also had a discharge record of gastro-oesophageal reflux (SIR = 7.5, 95% CI, 1.6–22.0 and SIR = 7.1, 95% CI, 3.1–14.0, respectively). No significant excess risk for oesophageal squamous-cell carcinoma or distal stomach cancer was observed. In conclusion, asthma is associated with a moderately elevated risk of developing oesophageal or gastric cardia adenocarcinoma. Special clinical vigilance vis-à-vis gastro-esophageal cancers seems unwarranted in asthmatic patients, but may be appropriate in those with clinically manifest gastro-oesophageal reflux.   http://www.bjcancer.com © 2001 Cancer Research Campaign PMID:11720467

  12. HMGA2 overexpression plays a critical role in the progression of esophageal squamous carcinoma

    PubMed Central

    Palumbo, Antonio; Meireles Da Costa, Nathalia; Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; de Sousa, Vanessa Paiva Leite; Martins, Ivanir; Nasciutti, Luiz Eurico; Fusco, Alfredo; Pinto, Luis Felipe Ribeiro

    2016-01-01

    Esophageal Squamous Cell Carcinoma (ESCC) is the most common esophageal tumor worldwide. However, there is still a lack of deeper knowledge about biological alterations involved in ESCC development. High Mobility Group A (HMGA) protein family has been related with poor outcome and malignant cell transformation in several tumor types. In this way, the aim of this study was to analyze the expression of HMGA1 and HMGA2 expression in ESCC and their role in crucial cellular features. We evaluated HMGA1 and HMGA2 mRNA expression in 52 paired ESCC and normal surrounding tissue samples by qRT-PCR. Here, we show that HMGA2, but not HMGA1, is overexpressed in ESCC samples. This result was further confirmed by the immunohistochemical analysis. Indeed, accordingly to mRNA expression data, HMGA2, but not HMGA1, was overexpressed in approximately 90% of ESCC samples, while it was barely expressed in the respective control. Conversely, HMGA1, but not HMGA2, was overexpressed in esophageal adenocarcinoma samples. Interestingly, HMGA2 abrogation attenuated the malignant phenotype of two ESCC cell lines, suggesting that HMGA2 overexpression is involved in ESCC progression. PMID:27027341

  13. HMGA2 overexpression plays a critical role in the progression of esophageal squamous carcinoma.

    PubMed

    Palumbo, Antonio; Da Costa, Nathalia Meireles; Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; de Sousa, Vanessa Paiva Leite; Martins, Ivanir; Nasciutti, Luiz Eurico; Fusco, Alfredo; Ribeiro Pinto, Luis Felipe

    2016-05-01

    Esophageal Squamous Cell Carcinoma (ESCC) is the most common esophageal tumor worldwide. However, there is still a lack of deeper knowledge about biological alterations involved in ESCC development. High Mobility Group A (HMGA) protein family has been related with poor outcome and malignant cell transformation in several tumor types. In this way, the aim of this study was to analyze the expression of HMGA1 and HMGA2 expression in ESCC and their role in crucial cellular features. We evaluated HMGA1 and HMGA2 mRNA expression in 52 paired ESCC and normal surrounding tissue samples by qRT-PCR. Here, we show that HMGA2, but not HMGA1, is overexpressed in ESCC samples. This result was further confirmed by the immunohistochemical analysis. Indeed, accordingly to mRNA expression data, HMGA2, but not HMGA1, was overexpressed in approximately 90% of ESCC samples, while it was barely expressed in the respective control. Conversely, HMGA1, but not HMGA2, was overexpressed in esophageal adenocarcinoma samples. Interestingly, HMGA2 abrogation attenuated the malignant phenotype of two ESCC cell lines, suggesting that HMGA2 overexpression is involved in ESCC progression.

  14. Prognostic relevance of nutritional status in patients with advanced esophageal cancer.

    PubMed

    Bollschweiler, Elfriede; Herbold, Till; Plum, Patrick; Hölscher, Arnulf H

    2013-03-01

    Evaluation of: Clavier JB, Antoni D, Atlani D et al. Baseline nutritional status is prognostic factor after definitive radiochemotherapy for esophageal cancer. Dis. Esoph. doi:10.1111/j.1442-2050.2012.01441.x (2012) (Epub ahead of print). The influence of nutritional status of patients with esophageal cancer on the effect of chemoradiation is not well studied. In a retrospective study of 143 patients with definitive chemoradiation, the authors show that malnutrition is a negative prognostic factor. In the Western industrial world, the incidence of high BMI has greatly increased over the past few decades, together with the incidence of esophageal adenocarcinoma. Studies analyzing the influence of being overweight on the outcome after esophagectomy showed that a very high BMI has a negative impact on a patient's survival. The interpretation of results from prognostic studies will be more complicated if several therapeutic procedures are combined, for example, neoadjuvant or adjuvant therapies combining chemoradiation or chemotherapy and esophagectomy. Prospective randomized studies including the nutritional status and immune competence for patients with advanced cancer of the esophagus are necessary.

  15. Baseline nutritional status is prognostic factor after definitive radiochemotherapy for esophageal cancer.

    PubMed

    Clavier, J-B; Antoni, D; Atlani, D; Ben Abdelghani, M; Schumacher, C; Dufour, P; Kurtz, J-E; Noel, G

    2014-08-01

    Identify prognostic factors for survival and patterns of treatment failure after definitive radiochemotherapy for esophageal cancer. Between 2003 and 2006, 143 patients with squamous cell carcinoma and adenocarcinoma of the esophagus were retrospectively reviewed. Median age was 65 years (42-81). Median radiation dose was 62.5 Gy (38-72) with 1.8-2 Gy fraction. Median follow-up was 20.8 months (2.8-92.4). Three and 5-year local recurrence-free survival rates were 58.3% and 50.9%. In univariate analysis, traversable esophageal stricture was a prognostic factor. Three, 5-year locoregional recurrence-free survival rates were 42.4% and 34.9%. In multivariate analysis, traversable esophageal stricture and stage < IIB were independent prognostic factors. Three and 5-year disease-free survival rates were 30.5% and 25.9%. In multivariate analysis, Nutritional Risk Index (NRI) ≥ 97.5 and performance status (PS) = 0 were independent prognostic factors. Median, 3, and 5-year overall survival rates were 22.1 months, 34.4%, and 19.8%. In multivariate analysis, independent prognostic factors were NRI ≥ 97.5 and PS = 0. Median survival times for the NRI classes (no denutrition, moderate and severe denutrition) were 29.5, 19.7, and 12 months (P = 0.0004), respectively. A major impact of baseline NRI was found in terms of survival; it should be included in future prospective trials.

  16. 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

  17. [Cancer procoagulant activity in cases of esophageal, stomach and colorectal cancer considering progression degree and histological type of cancer].

    PubMed

    Kozuszko, B; Skrzydlewski, Z; Sulkowska, M; Snarska, J; Kozłowski, M; Skrzydlewska, E; Zalewski, B

    2001-09-01

    The cancer procoagulant activity has been evaluated in homogenates of esophagal, stomach and colorectal cancer tissues and in the blood serum of patients with these neoplasms's. Activity of CP was significantly higher in examined material than in control. The correlation between CP activity and progression degree as well as histological type was affirmed. The higher activity of CP in homogenates as well as in serum was observed in cases with higher degree of clinical progression and smaller activity of this enzyme corresponded with lower degree of the cancer progression. The highest activity of CP was observed in the cases of adenocarcinoma whereas the lowest in cases of squamous cell carcinoma. Higher activity of CP in homogenates of examined tissues correlated with higher activity of this enzyme in the serum. Activity of CP depended on the tissue localisation of the cancer and the highest was in the cases of stomach cancers whereas the lowest was in the cases of esophagal cancer.

  18. 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....

  19. 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....

  20. 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....

  1. 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....

  2. 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....

  3. 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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  4. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  5. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  6. 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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  7. 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 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  8. Esophageal Impedance Monitoring: Clinical Pearls and Pitfalls.

    PubMed

    Ravi, Karthik; Katzka, David A

    2016-09-01

    The development of intraluminal esophageal impedance monitoring has improved our ability to detect and measure gastroesophageal reflux without dependence on acid content. This ability to detect previously unrecognized weak or nonacid reflux episodes has had important clinical implications in the diagnosis and management of gastroesophageal reflux disease (GERD). In addition, with the ability to assess bolus transit within the esophageal lumen, impedance monitoring has enhanced the recognition and characterization of esophageal motility disorders in patients with nonobstructive dysphagia. The assessment of the intraluminal movement of gas and liquid has also been proven to be of diagnostic value in conditions such as rumination syndrome and excessive belching. Further, alternative applications of impedance monitoring, such as the measurement of mucosal impedance, have provided novel insights into assessing esophageal mucosal integrity changes as a consequence of inflammatory change. Future applications for esophageal impedance monitoring also hold promise in esophageal conditions other than GERD. However, despite all of the clinical benefits afforded by esophageal impedance monitoring, important clinical and technical shortcomings limit its diagnostic value and must be considered when interpreting study results. Overinterpretation of studies or application of impedance monitoring in patients can have deleterious clinical implications. This review will highlight the clinical benefits and limitations of esophageal impedance monitoring and provide clinical pearls and pitfalls associated with this technology.

  9. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal dilator. 876.5365 Section 876.5365 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5365 Esophageal dilator....

  10. Esophageal Impedance Monitoring: Clinical Pearls and Pitfalls.

    PubMed

    Ravi, Karthik; Katzka, David A

    2016-09-01

    The development of intraluminal esophageal impedance monitoring has improved our ability to detect and measure gastroesophageal reflux without dependence on acid content. This ability to detect previously unrecognized weak or nonacid reflux episodes has had important clinical implications in the diagnosis and management of gastroesophageal reflux disease (GERD). In addition, with the ability to assess bolus transit within the esophageal lumen, impedance monitoring has enhanced the recognition and characterization of esophageal motility disorders in patients with nonobstructive dysphagia. The assessment of the intraluminal movement of gas and liquid has also been proven to be of diagnostic value in conditions such as rumination syndrome and excessive belching. Further, alternative applications of impedance monitoring, such as the measurement of mucosal impedance, have provided novel insights into assessing esophageal mucosal integrity changes as a consequence of inflammatory change. Future applications for esophageal impedance monitoring also hold promise in esophageal conditions other than GERD. However, despite all of the clinical benefits afforded by esophageal impedance monitoring, important clinical and technical shortcomings limit its diagnostic value and must be considered when interpreting study results. Overinterpretation of studies or application of impedance monitoring in patients can have deleterious clinical implications. This review will highlight the clinical benefits and limitations of esophageal impedance monitoring and provide clinical pearls and pitfalls associated with this technology. PMID:27325223

  11. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... source of EAS Local Area messages. An LP source is responsible for coordinating the carriage of common... as specified in its EAS Local Area Plan. If it is unable to carry out this function, other LP sources in the Local Area may be assigned the responsibility as indicated in State and Local Area Plans....

  12. 47 CFR 11.18 - EAS Designations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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 LP source is responsible for coordinating the carriage of common emergency messages from sources such as the National Weather Service or local emergency management...

  13. 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.

  14. 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

  15. Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

    PubMed Central

    Gallerani, Giulia; Fabbri, Francesco

    2016-01-01

    Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted. PMID:27527155

  16. [Endoscopic surgery for benign esophageal diseases].

    PubMed

    Ozawa, Soji

    2006-07-01

    Gastroesophageal reflux disease (GERD) and esophageal achalasia are common benign esophageal diseases. Today minimally invasive surgery is recommended to treat these diseases. Surgical indications for GERD are failure of medical management, medical complications attributable to a large hiatal hernia, 'atypical' symptoms (asthma, hoarseness, cough, chest pain, aspiration), etc. according to the Society of American Gastrointestinal Endoscopic Surgeons (SAGES) guidelines. Laparoscopic Nissen fundoplication has emerged as the most widely accepted procedure for GERD patients with normal esophageal motility. Partial fundoplication (e.g., Toupet fundoplication) is also considered to decrease the possibility of postoperative dysphagia. Although pneumatic dilatation has been the first line treatment for esophageal achalasia, laparoscopic Heller myotomy and partial fundoplication (e.g., Dor fundoplication) to prevent reflux is preferred by most gastroenterologists and surgeons as the primary treatment modality. Laparoscopic surgery for GERD and esophageal achalasia are effective in most patients and safe in all patients. Finally, laparoscopic surgery should be performed only by skilled surgeons.

  17. Unusual Presentation of a Metastatic Esophageal Carcinoma

    PubMed Central

    Orlicka, Katarzyna; Maynard, Stéphanie; Bouin, Mickael

    2012-01-01

    Esophageal cancer most commonly presents with upper digestive symptoms such as dysphagia. Lymph nodes are among the most common metastatic sites of this type of cancer. We report the case of a 53-year-old man presenting with unusual sole presenting features of esophageal cancer. The patient sought medical attention for abdominal pain without dysphagia, which was first investigated with an abdominal computed tomography scan. A large abdominal mass was discovered on imaging. Biopsies of this mass were in keeping with esophageal squamous cell cancer. With this finding, gastroscopy was performed, confirming the presence of primary esophageal cancer. This is a rare presentation of esophageal cancer without upper gastrointestinal symptoms. This case reinforces the value of biopsy for any neoplastic mass, especially in a context of unusual symptoms. PMID:22679417

  18. Spontaneous colonic adenocarcinoma in marmosets.

    PubMed

    Lushbaugh, C C; Humason, G L; Swartzendruber, D C; Richter, C B; Gengozian, N

    1978-01-01

    We find that colonic adenocarcinoma, which is an extremely rare neoplasm of all animals except man and carcinogen-treated rodents, occurs spontaneously in some marmosets. The cotton-topped Saguinus oedipus oedipus is particularly prone to develop it, but we have found it also at necropsy in Callimico goeldii (Goeldi's marmoset). Numerous metastases to regional lymph nodes develop. The cancers arise de novo in the mucosa and early invade the submucosa and lymphatic apparatus and paracolonic lymph nodes. These findings and the continuing occurrence of this cancer in our colony suggests that the marmoset may be the long-sought primate model for experimental intestinal carcinogenesis.

  19. Novel Therapeutics for Pancreatic Adenocarcinoma.

    PubMed

    Lowery, Maeve A; O'Reilly, Eileen M

    2015-08-01

    The last decade has seen significant developments in the use of combination systemic therapy for advanced pancreatic ductal adenocarcinoma (PDAC), with median survival approaching 1 year for select patients treated with FOLFIRINOX in the metastatic setting. However, it is sobering that these developments have been achieved with the use of traditional cytotoxics rather than from successes in the more modern fields of molecularly targeted therapies or immunotherapy. This article highlights several promising therapeutic approaches to PDAC currently under clinical evaluation, including immune therapies, molecularly targeted therapies, strategies for stromal depletion, and targeted therapy for genetically selected patients.

  20. Oncocytic adenocarcinoma of salivary glands.

    PubMed

    Goode, R K; Corio, R L

    1988-01-01

    Oncocytic adenocarcinoma of salivary gland origin is an extremely rare neoplasm. The diagnosis is established on the basis of oncocytic cellular features in conjunction with dysplastic change. These dysplastic changes may occur in benign oncocytomas or arise de novo. The tumor occurs most commonly in the parotid glands of persons over 60 years of age. Tumors that measure less than 2 cm at the initial surgical procedure appear to have a better prognosis than larger tumors. Aggressive surgical intervention at the initial presentation of the neoplasm, compared to simple enucleation, seems to offer a more favorable prognosis. Recurrence is an ominous feature. Metastasis, when it occurs, is widespread.

  1. [Clinical features and pathophysiology of acute esophageal mucosal lesion].

    PubMed

    Ihara, Yutaro; Hizawa, Kazuoki; Fujita, Kouhei; Matsuno, Yuichi; Sakuma, Tsutomu; Esaki, Motohiro; Iida, Mitsuo

    2016-04-01

    Acute esophageal mucosal lesions (AEMLs) are categorized into black esophagitis (type B) and non-black esophagitis (type NB) on endoscopy. To clarify the distinct pathophysiology, we compared the clinical features and hematological findings at onset among 17 patients with type B esophagitis and 6 patients with type NB esophagitis. In type B esophagitis, time to endoscopy after onset was significantly shorter, and blood levels of lactate, urea nitrogen, creatinine, and glucose were higher than in type NB esophagitis. However, there were no significant intergroup differences in the incidences of other predisposing factors, such as diabetic ketoacidosis or esophageal hernias. These findings suggest that AEMLs are caused by acid reflux and peripheral vascular insufficiency, the latter being more associated with type B esophagitis by its etiology. In addition, blood lactate may indicate the severity of AEML, leading to black esophagitis. PMID:27052393

  2. Duodenal Adenocarcinoma Metastatic to the Breast

    PubMed Central

    Yu, Haibo; Song, Hongliang; Jiang, Yi

    2016-01-01

    Abstract Duodenal adenocarcinoma, a very rare malignant gastrointestinal tumor, mainly metastasizes via the lymphatic system. Metastases from duodenal adenocarcinomas to the breast are very uncommon. A 31-year-old woman presented at our department with a left breast tumor. She had a past medical history of duodenal adenocarcinoma. Physical examination on admission confirmed a 2.5-cm-diameter tumor in the outer lower quadrant of the left breast. Computed tomography (CT) examination showed a soft lesion with tissue-like density and enlarged axillary lymph nodes. Local excision was performed to remove the breast lesion. The findings of cytologic, histologic, and immunohistochemistry examination indicated a breast metastasis from the previous duodenal adenocarcinoma. The patient was treated with palliative chemotherapy. Metastases from duodenal adenocarcinoma to the breast are rare. The diagnosis depends on medical history, imaging, and pathologic examination including immunohistochemistry. An accurate diagnosis is important to avoid unnecessary surgery. PMID:26986146

  3. Giant mid-esophageal diverticulum. Conservative treatment of postoperative leakage.

    PubMed

    Dallatomasina, S; Casaccia, M; Chessa, M; Serrano, J; Nardi, I; Troilo, B; Miggino, M; Valente, U

    2009-01-01

    Mid-esophageal diverticula are rare entities. Only symptomatic patients usually receive surgical treatment. Esophageal leakage is one of the most common complications after these procedures. Though in literature, operative management is the preferred treatment for esophageal fistula, conservative approach is described in case of small leaks. We report a case of an operated giant mid-esophageal diverticulum complicated with an esophageal fistula. The patient underwent a surgical treatment and recovered completely.

  4. 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

  5. Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.

    PubMed

    Prithviraj, G K; Baksh, K; Fulp, W; Meredith, K; Hoffe, S; Shridhar, R; Almhanna, K

    2015-01-01

    Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we retrospectively present our single center experience. Between 1998 and 2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly area under the curve 5 and paclitaxel predominantly 175 mg/m(2)) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from diagnosis to death or last follow up, and progression-free survival was defined at time from cycle 1 to, progression or last follow up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Of the 134 patients evaluated, the median age at diagnosis was 65 years. Disease control rate was 62.6% (complete response: 11%, partial response: 28%, stable disease: 33%). Median overall survival from date of initial diagnosis was 15.5 months (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 5.3 months (95% CI 0.34-0.5). Grade III or greater toxicity occurred in 26.1% of patients. The most common grade III toxicities were neutropenia and neuropathy, present in 14.2% and 3.7% of the total study population, respectively. In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population.

  6. Advanced mucinous adenocarcinoma in pregnancy.

    PubMed

    Angioli, R; Yasin, S; Estape, R; Janicek, M; Adra, A; Sopo, C; Minhaj, M; Penalver, M

    1997-01-01

    The incidence of masses in pregnancy is estimated to occur in 1/81 to 1/2,500 pregnancies. The development of colorectal carcinoma during pregnancy is a more rare event, with less than 30 cases above the peritoneal reflection reported in the last 70 years. The differential diagnosis of mucinous adenocarcinoma of ovarian vs. gastrointestinal origin is often difficult. We report a pregnant patient affected by advanced colorectal cancer, who presented with an asymptomatic unilateral adnexal mass on ultrasound. A 28-year old woman was referred to our hospital after a routine ultrasound examination at 26 weeks gestation showing a right adnexal mass. At elective exploratory laparotomy, the patient was found to have metastatic mucinous adenocarcinoma. Diagnostic and treatment choices of such a cancer in a pregnant patient were explored. The final diagnosis of colorectal cancer was made only at the time of a subsequent emergency laparotomy. The goal of an obstetrician/gynecologist and other care givers of pregnant patients, is to achieve a healthy mother and child. Unfortunately, physicians may unwillingly sacrifice the health of the mother by denying or delaying her procedures or treatments simply because she is pregnant. It is especially important in the case of adnexal masses and their related pathology, due to the difficulty in detection and management of such cases during pregnancy, that doctors actively assume the responsibility of assuring that pregnant patients receive the proper care they need.

  7. 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...

  8. 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...

  9. 7 CFR 1794.71 - Adoption of an EA.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 12 2013-01-01 2013-01-01 false Adoption of an EA. 1794.71 Section 1794.71... AGRICULTURE (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Adoption of Environmental Documents § 1794.71 Adoption of an EA. RUS may adopt a Federal EA or EIS or a portion thereof as its EA. RUS shall make the...

  10. 7 CFR 1794.71 - Adoption of an EA.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Adoption of an EA. 1794.71 Section 1794.71... AGRICULTURE (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Adoption of Environmental Documents § 1794.71 Adoption of an EA. RUS may adopt a Federal EA or EIS or a portion thereof as its EA. RUS shall make the...

  11. 7 CFR 1794.71 - Adoption of an EA.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 12 2012-01-01 2012-01-01 false Adoption of an EA. 1794.71 Section 1794.71... AGRICULTURE (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Adoption of Environmental Documents § 1794.71 Adoption of an EA. RUS may adopt a Federal EA or EIS or a portion thereof as its EA. RUS shall make the...

  12. 7 CFR 1794.71 - Adoption of an EA.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 12 2011-01-01 2011-01-01 false Adoption of an EA. 1794.71 Section 1794.71... AGRICULTURE (CONTINUED) ENVIRONMENTAL POLICIES AND PROCEDURES Adoption of Environmental Documents § 1794.71 Adoption of an EA. RUS may adopt a Federal EA or EIS or a portion thereof as its EA. RUS shall make the...

  13. Role of advanced diagnostics for eosinophilic esophagitis.

    PubMed

    Hirano, Ikuo

    2014-01-01

    In eosinophilic esophagitis (EoE), diagnostic tests aid in the identification of pathophysiologic consequences and accurate detection of the disease. The EoE Endoscopic Reference Score (EREFS) classifies and grades the severity of the five major endoscopically identified esophageal features of EoE (edema, rings, exudates, furrows and strictures). The EREFS may be useful in the evaluation of disease severity and as an objective outcome of response to therapy. pH monitoring identifies the presence of abnormal degrees of acid exposure in the esophagus that characterizes gastroesophageal reflux disease. The presence of acid reflux, however, does not indicate that the reflux is responsible for esophageal eosinophilia. Esophageal manometry has not demonstrated a characteristic abnormality with sufficient sensitivity to make the test of diagnostic value in clinical practice. On the other hand, manometric characteristics of esophageal pressurization and longitudinal muscle dysfunction may help identify important pathophysiologic consequences of EoE. Esophageal impedance testing has demonstrated increased baseline mucosal impedance that correlates with increased epithelial permeability in EoE. Reduced mucosal integrity may provide intraluminal allergens access to antigen-presenting cells, serving as an early event in the pathogenesis of EoE. The functional luminal impedance probe (FLIP) provides quantitative assessment of esophageal mural compliance, a physiologic correlate of remodeling in EoE. Studies using FLIP have associated reductions in esophageal distensibility in EoE with the important outcome of food impaction risk. Finally, confocal endomicroscopy, multiphoton fluorescence microscopy and novel eosinophil-enhancing contrast agents are emerging methods that may allow for in vivo visualization of esophageal eosinophilic inflammation, thereby improving the detection and understanding of this emerging disease. PMID:24603385

  14. 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

  15. 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

    2016-06-03

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  16. [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

  17. Updates on esophageal and gastric cancers

    PubMed Central

    Gallo, Amy; Cha, Charles

    2006-01-01

    Esophageal and gastric cancers are both common and deadly. Patients present most often after disease progression and survival is therefore poor. Due to demographic variability and recent changes in disease incidence, much emphasis has been placed on studying risk factors for both esophageal and gastric cancers. However, with increasing understanding of these diseases, low survival rates persist and continued intensive studies are necessary to optimize treatment plans. This review article discusses updates in the evolving epidemiology, clinical presentation, risk factors, and diagnostic and treatment modalities of esophageal and gastric cancers. PMID:16718845

  18. 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. PMID:27144142

  19. [Laparoscopic surgery for esophageal achalasia].

    PubMed

    Ozawa, S; Ando, N; Ohgami, M; Kitagawa, Y; Kitajima, M

    2000-04-01

    Laparoscopic surgery for esophageal achalasia was first reported by Shimi et al. in 1991. Subsequently the procedure has been performed all over the world and laparoscopic Heller myotomy and Dor fundoplication (Heller and Dor operation) is now thought to be the operation of first choice. It is indicated for patients who are resistant to medical therapy (calcium blocker etc.) or have pneumatic dilatation and those with frequent aspiration at night. As Csendes et al. reported that surgical treatment was better than pneumatic dilatation and as laparoscopic surgery is less invasive, the indications for the laparoscopic Heller and Dor operation can include all achalasia patients except those who respond to medical therapy, do not accept surgery, or cannot tolerate surgery. We successfully performed the laparoscopic Heller and Dor operation on 22 patients, all of whom had an uneventful postoperative course. Manometric evaluation, endoscopic examination, and 24-hour pH monitoring showed good results. There are six important technical points: 1) flexible laparoscopy; 2) pneumoperitoneum; 3) gauze in the abdominal cavity to absorb blood; 4) laparosonic coagulating shears; 5) extracorporeal knot-tying technique; and 6) intracorporeal knot-tying technique. If an experienced surgeon is in charge, the laparoscopic Heller and Dor operation is an ideal, minimally invasive treatment for esophageal achalasia.

  20. Neoadjuvant Paclitaxel Poliglumex (PPX), Cisplatin, and Radiation (RT) for Esophageal Cancer

    PubMed Central

    Ng, T.; Fontaine, J.; Dipetrillo, T.; Suntharalingam, M.; Horiba, N.; Oldenburg, N.; Oconnor, B.; Perez, K.; Birnbaum, A.; Battafarano, R.; Burrows, W.; Safran, H.

    2010-01-01

    Background: Paclitaxel poliglumex (PPX) is a drug conjugate that links paclitaxel to poly-L-glutamic acid thereby increasing its radiation enhancement factor to 4.0–8.0 compared to 1.5–2.0 for paclitaxel. In previous phase I studies, The Brown University Oncology Group evaluated PPX with concurrent radiation and PPX/cisplatin/RT. A phase II study was subsequently performed to evaluate the pathologic response rate of neoadjuvant PPX, cisplatin, and radiation for patients with esophageal cancer. Methods: Eligible patients had pathologically confirmed adenocarcinoma or squamous cell carcinoma of the esophagus or GE junction with no evidence of distant metastasis. Patients received weekly PPX 50 mg/m2 and cisplatin 25 mg/m2 for 6 weeks with concurrent 50.4 Gy of radiation. Six to eight weeks after completion of chemoradiotherapy, patients underwent surgical resection. Results: The study has completed accrual of 40 patients, 37 with adenocarcinoma and 3 with squamous cell cancer. The median age is 62 years. Toxicity data are available for the first 35 patients. Four of 35 patients experienced grade 4 non-hematologic toxicities, which included electrolyte abnormalities, glucose intolerance, hypersensitivity reaction, and thromboembolus. Eleven of 35 patients had grade 3 non-hematologic toxicities including electrolyte abnormalities (n=5), nausea (n=3), dysphagia (n=2), fatigue (n=2), glucose intolerance (n=2), and hypersensitivity reaction (n=1). Grade 3 anorexia was reported in only 1 patient who subsequently was given TPN. No patients required a feeding tube. There were no grade 4 hematologic toxicities; grade 3 hematologic toxicities included neutropenia (n=2) and anemia (n=1). Of the first 28 patients undergoing surgery, all with adenocarcinoma, 7 of 28 (25%) have had a pathologic complete response. Conclusion: PPX, cisplatin and concurrent radiation is a well tolerated, easily administered regimen for esophageal cancer with a very low incidence of significant

  1. Palliative Treatment of Esophageal Cancer.

    PubMed

    Ahmad; Goosenberg; Frucht; Coia

    1994-07-01

    Palliative interventions for advanced esophageal cancer include surgery, radiation therapy, chemotherapy, chemoradiation, endoscopic procedures, and combinations of the above. Palliative esophagectomy or bypass procedures are difficult to justify in these patients because their life expectancy is so short. Palliative external beam radiation to doses of 50 to 60 Gy is successful in 50% to 70% of patients. The addition of brachytherapy may improve these results. One third to one half of patients treated with radiation develop benign or maglinant stricture. Although response rates to combination chemotherapy are only 50% at best, the majority of patients do have improvement of dysphagia. These regimens are commonly used as part of a multidisciplinary approach with radiation andøor surgery, rather than as a sole modality of treatment. Chemoradiation regimens results in better survival than treatment with radiation alone, and provide palliation of dysphagia in up to 90% of patients. Although acute toxicity of chemoradiation is more severe than radiation alone, this is of limited duration. Chemoradiation may be the treatment of choice for the majority of patients with locally advanced esophageal cancer. Endoscopic techniques are available that provide palliation of dysphagia. The most commonly used technique is esophageal dilatation, either alone or before performing other palliative procedures such as laser therapy or stent placement. The most significant limitation of dilatation alone is that palliation is short-lived and most patients require repeat dilatations. Esophageal stents offer a high degree of palliation, but procedure-related morbidity and mortality rates are not insignificant. Expandable metal stents are associated with few complications but tumor ingrowth through the metallic mesh is frequent. Conventional plastic stents are not affected by tumor ingrowth but can migrate. Endoscopic laser therapy also provides symptoms relief and complication rates are

  2. Clinicopathologic features and treatment outcomes of patients with human epidermal growth factor receptor 2-positive adenocarcinoma of the esophagus and gastroesophageal junction.

    PubMed

    Phillips, B E; Tubbs, R R; Rice, T W; Rybicki, L A; Plesec, T; Rodriguez, C P; Videtic, G M; Saxton, J P; Ives, D I; Adelstein, D J

    2013-04-01

    Human epidermal growth factor receptor 2 (HER2) is overexpressed in 21% of gastric and 33% of gastroesophageal junction (GEJ) adenocarcinomas. Trastuzumab has been approved for metastatic HER2-positive gastric/GEJ cancer in combination with chemotherapy. This retrospective analysis was undertaken to better define the clinicopathologic features, treatment outcomes, and prognosis in patients with HER2-positive adenocarcinoma of the esophagus/GEJ. Pathologic specimens from 156 patients with adenocarcinoma of the esophagus/GEJ treated on clinical trials with chemoradiation and surgery were tested for HER2. Seventy-six patients also received 2 years of gefitinib. Baseline characteristics and treatment outcomes of the HER2-positive and negative patients were compared both in aggregate and separately for each of the two trials. Of 156 patients, 135 had sufficient pathologic material available for HER2 assessment. HER2 positivity was found in 23%; 28% with GEJ primaries and 15% with esophageal primaries (P= 0.10). There was no statistical difference in clinicopathologic features between HER2-positive and negative patients except HER2-negative tumors were more likely to be poorly differentiated (P < 0.001). Locoregional recurrence, distant metastatic recurrence, any recurrence, and overall survival were also statistically similar between the HER2-positive and the HER2-negative groups, in both the entire cohort and in the gefitinib-treated subset. Except for tumor differentiation, HER2-positive and negative patients with adenocarcinoma of the esophagus and GEJ do not differ in clinicopathologic characteristics and treatment outcomes. Given the demonstrated benefit of trastuzumab in HER2-positive gastric cancer and the similar incidence of HER2 overexpression in esophageal/GEJ adenocarcinoma, further evaluation of HER2-directed therapy in this disease seems indicated.

  3. Registration of Neutrons Within 2 Milliseconds after EAS

    NASA Astrophysics Data System (ADS)

    JȨDRZEJCZAK, K.; Karczmarczyk, J.; Kasztelan, M.; Petrochenkov, S. A.; Polański, A.; Swarzyński, J.; Szabelski, J.; Wibig, T.

    We register an excess of signals from neutron detectors within a few milliseconds after passage of EAS front in Łódź EAS array. The most probable explanation is that neutrons are produced in EAS hadron interactions with lead block of muon detector. These neutrons diffuse and are thermalized before the detection. We present experimental data and results of simulations using MCNP code. This "new EAS observable" can be used as inexpensive hadron detector in EAS.

  4. [Alpha Fetoprotein-producing Lung Adenocarcinoma].

    PubMed

    Komori, Kazuyuki; Tabata, Toshiharu; Sato, Kimiaki; Katsumata, Hiroshi; Minowa, Muneo; Kondo, Takashi

    2015-11-01

    We report a case of alpha fetoprotein (AFP) -producing lung adenocarcinoma. A 53-year-old man was referred to our hospital due to right pneumothorax. Computed tomography showed right moderate pneumothorax, a solid tumor in the upper lobe (S3) and mediastinal lymph node swelling. The serum AFP level was as high as 223.0 ng/ml. Frozen examination revealed a low-differentiated adenocarcinoma. Based on the pathological and immunohistochemical findings, the tumor was diagnosed as AFP-producing lung adenocarcinoma.

  5. Colorectal adenocarcinoma in Crohn's disease.

    PubMed Central

    Ribeiro, M B; Greenstein, A J; Sachar, D B; Barth, J; Balasubramanian, S; Harpaz, N; Heimann, T M; Aufses, A H

    1996-01-01

    OBJECTIVE: The authors' aim was to review the clinical features and estimate the long-term survival of patients with colorectal carcinoma complicating Crohn's disease. SUMMARY BACKGROUND DATA: Recent studies have demonstrated a significantly increased risk of colorectal carcinoma in patients with Crohns disease. METHODS: The authors reviewed retrospectively the medical records of 30 patients with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1989 in whom colorectal adenocarcinoma developed. All patients were operated on and follow-up was complete for all patients to 10 years after operation, to the time of death, or to the closing date of the study in December 1989. RESULTS: The 30 patients in the series had 33 colorectal adenocarcinomas; three patients (10%) presented with two synchronous cancers. The patients were relatively young (mean age, 53 years) and had long-standing Crohn's disease (duration >20 years in 87%). The 5-year actuarial survival was 44% for the overall series: 100% for stage A, 86% for stage B, 60% for stage C. All five patients with excluded bowel tumor died of large bowel cancer within 2.4 years; by contrast, the actuarial 5-year survival for patients with in-continuity tumors was 56%. CONCLUSIONS: The incidence, characteristics, and prognosis of colorectal carcinoma complicating Crohn's disease are similar to the features of cancer in ulcerative colitis, including young age, multiple neoplasms, long duration of disease, and greater than a 50% 5-year survival rate (without excluded loops). These observations suggest the advisability of surveillance programs for Crohn's disease of the colon similar to those for ulcerative colitis of comparable duration and extent. PMID:8597513

  6. Lysyl oxidase-like 2 expression is increased in colon and esophageal tumors and associated with less differentiated colon tumors.

    PubMed

    Fong, Sheri F T; Dietzsch, Erin; Fong, Keith S K; Hollosi, Peter; Asuncion, Lloyd; He, Qingping; Parker, M Iqbal; Csiszar, Katalin

    2007-07-01

    Lysyl oxidase-like 2 (LOXL2) belongs to an amine oxidase family whose members have been implicated in crosslink formation in stromal collagens and elastin, cell motility, and tumor development and progression. We previously demonstrated the association between increased LOXL2 expression and invasive/metastatic behavior in human breast cancer cells and mouse squamous and spindle cell carcinomas, interaction between LOXL2 and SNAIL in epithelial-mesenchymal transition, and localization of the LOXL2 gene to 8p21.2-21.3, within a minimally deleted region in several cancers, including colon and esophagus. In the present study, we analyzed LOXL2 expression in colon and esophageal tumors, and explored methylation as a regulator of LOXL2 expression. Immunohistochemistry using normal tissues demonstrated intracellular localization of LOXL2 in colonic enteroendocrine cells and esophageal squamous cells at the luminal surface, but not in mitotically active cells. Tissue array analysis of 52 colon adenocarcinomas and 50 esophageal squamous cell carcinomas revealed presence of LOXL2 expression in 83 and 92% of the samples, respectively, and a significant association between increased number of LOXL2-expressing cells and less-differentiated colon carcinomas. We determined that the methylation status of the 1150 bp 5' CpG island may contribute to the regulation of the gene. Loss of heterozygosity studies, using a microsatellite within intron 4 of the LOXL2 gene, revealed that loss of LOXL2 was unlikely to play a major role in either colon or esophageal tumors. These results suggest that increased LOXL2 expression in colon and esophageal cancer may contribute to tumor progression.

  7. Esophageal cancer epidemiology in blacks and whites: racial and gender disparities in incidence, mortality, survival rates and histology.

    PubMed Central

    Baquet, Claudia R.; Commiskey, Patricia; Mack, Kelly; Meltzer, Stephen; Mishra, Shiraz I.

    2005-01-01

    BACKGROUND: Esophageal cancer rate disparities are pronounced for blacks and whites. This study presents black-white esophageal cancer incidence, mortality, relative survival rates, histology and trends for two five-year time periods--1991-1995 and 1996-2000--and for the time period 1991-2000. METHODS: The study used data from the National Cancer Institute's population-based Surveillance Epidemiology End Results (SEER) program with submission dates 1991-2000. Age-adjusted incidence, mortality, relative survival rates and histology for esophageal carcinoma were calculated for nine SEER cancer registries for 1991-2000. Rates were analyzed by race and gender for changes over specified time periods. RESULTS: Esophageal cancer age-adjusted incidence of blacks was about twice that of whites (8.63 vs. 4.39/100,000, p < 0.05). Age-adjusted mortality for blacks, although showing a declining trend, was nearly twice that of whites (7.79 vs. 3.96, p < 0.05). Although survival was poor for all groups, it was significantly poorer in blacks than in whites. Squamous cell carcinoma was more commonly diagnosed in blacks and white females, whereas adenocarcinoma was more common among white males (p < 0.001). CONCLUSIONS: Racial disparities in esophageal cancer incidence, mortality, survival and histology exist. Survival rates from this disease have not significantly improved over the decade. These data support the need for advances in prevention, early detection biomarker research and research on new, more effective treatment modalities for this disease. Images Figure 1 PMID:16334494

  8. Inhibition of Notch signaling enhances transdifferentiation of the esophageal squamous epithelium towards a Barrett's-like metaplasia via KLF4.

    PubMed

    Vega, Maria E; Giroux, Véronique; Natsuizaka, Mitsuteru; Liu, Mingen; Klein-Szanto, Andres J; Stairs, Douglas B; Nakagawa, Hiroshi; Wang, Kenneth K; Wang, Timothy C; Lynch, John P; Rustgi, Anil K

    2014-01-01

    Barrett's esophagus (BE) is defined as an incomplete intestinal metaplasia characterized generally by the presence of columnar and goblet cells in the formerly stratified squamous epithelium of the esophagus. BE is known as a precursor for esophageal adenocarcinoma. Currently, the cell of origin for human BE has yet to be clearly identified. Therefore, we investigated the role of Notch signaling in the initiation of BE metaplasia. Affymetrix gene expression microarray revealed that BE samples express decreased levels of Notch receptors (NOTCH2 and NOTCH3) and one of the the ligands (JAG1). Furthermore, BE tissue microarray showed decreased expression of NOTCH1 and its downstream target HES1. Therefore, Notch signaling was inhibited in human esophageal epithelial cells by expression of dominant-negative-Mastermind-like (dnMAML), in concert with MYC and CDX1 overexpression. Cell transdifferentiation was then assessed by 3D organotypic culture and evaluation of BE-lineage specific gene expression. Notch inhibition promoted transdifferentiation of esophageal epithelial cells toward columnar-like cells as demonstrated by increased expression of columnar keratins (K8, K18, K19, K20) and glandular mucins (MUC2, MUC3B, MUC5B, MUC17) and decreased expression of squamous keratins (K5, K13, K14). In 3D culture, elongated cells were observed in the basal layer of the epithelium with Notch inhibition. Furthermore, we observed increased expression of KLF4, a potential driver of the changes observed by Notch inhibition. Interestingly, knockdown of KLF4 reversed the effects of Notch inhibition on BE-like metaplasia. Overall, Notch signaling inhibition promotes transdifferentiation of esophageal cells toward BE-like metaplasia in part via upregulation of KLF4. These results support a novel mechanism through which esophageal epithelial transdifferentiation promotes the evolution of BE.

  9. The identification of gamma ray induced EAS

    NASA Technical Reports Server (NTRS)

    Blake, P. R.; Nash, W. F.

    1985-01-01

    Some of the penetrating particles in gamma-induced EAS from Cygnus X-3 observed by a single layer of flash-bulbs under 880 g cm/2 concrete, may be punched through photons rather than muons. An analysis of the shielded flash-tube response detected from EAS is presented. The penetration of the electro-magnetic component through 20 cm of Pb is observed at core distances approx. 10 m.

  10. Managing eosinophilic esophagitis: challenges and solutions

    PubMed Central

    Shah, Nisha A; Albert, Dustin M; Hall, Noah M; Moawad, Fouad J

    2016-01-01

    Eosinophilic esophagitis (EoE) is a chronic and progressive immune-mediated condition defined by symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa. Therapies consist of anti-eosinophilic medications and specialized diets aimed to decrease the progression of EoE and alleviate its symptoms, namely, dysphagia and food impaction. Assessing response to therapy remains challenging, as treatment end points are not well defined and currently consist of clinical, histologic, and endoscopic features. Newer validated measures may help standardize treatment end points. Emerging data support the use of maintenance therapy, which may reduce disease progression. Optimal dosages, delivery techniques, and duration of treatment need to be determined. When features of fibrostenosis develop, esophageal dilation is a safe and effective adjunctive strategy for improving symptoms. In EoE cases refractory to conventional treatments, newer therapies targeting inflammatory mediators and cytokines are on the horizon. PMID:27695356

  11. Regenerative Medicine Strategies for Esophageal Repair

    PubMed Central

    Londono, Ricardo

    2015-01-01

    Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

  12. Managing eosinophilic esophagitis: challenges and solutions

    PubMed Central

    Shah, Nisha A; Albert, Dustin M; Hall, Noah M; Moawad, Fouad J

    2016-01-01

    Eosinophilic esophagitis (EoE) is a chronic and progressive immune-mediated condition defined by symptoms of esophageal dysfunction and dense eosinophilic infiltration of the esophageal mucosa. Therapies consist of anti-eosinophilic medications and specialized diets aimed to decrease the progression of EoE and alleviate its symptoms, namely, dysphagia and food impaction. Assessing response to therapy remains challenging, as treatment end points are not well defined and currently consist of clinical, histologic, and endoscopic features. Newer validated measures may help standardize treatment end points. Emerging data support the use of maintenance therapy, which may reduce disease progression. Optimal dosages, delivery techniques, and duration of treatment need to be determined. When features of fibrostenosis develop, esophageal dilation is a safe and effective adjunctive strategy for improving symptoms. In EoE cases refractory to conventional treatments, newer therapies targeting inflammatory mediators and cytokines are on the horizon.

  13. 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

  14. Alcohol, Obesity Could Raise Esophageal Cancer Risk

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_160133.html Alcohol, Obesity Could Raise Esophageal Cancer Risk A third ... now linked to 11 types of cancer and alcohol links to six," she said in an institute ...

  15. Multidisciplinary management for esophageal and gastric cancer.

    PubMed

    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.

  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. 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

  18. RELATIONSHIP BETWEEN ESOPHAGITIS GRADES AND HELICOBACTER PYLORI

    PubMed Central

    RIBEIRO, Patrícia Fernanda Saboya; KUBRUSLY, Luiz Fernandao; NASSIF, Paulo Afonso Nunes; RIBEIRO, Irma Cláudia Saboya; BERTOLDI, Andressa de Souza; BATISTÃO, Venessa Caroline

    2016-01-01

    ABSTRACT Background: The Helicobacter pylori infection (HP) is related to the development of gastric lesions and lymphoma; however, it is not known if there is a relation with gastroesophageal reflux disease and reflux esophagitis. Aim: To evaluate HP's relationship with esophagitis in patients undergoing upper endoscopy. Methods: Observational, retrospective and cross-sectional study, being evaluated 9576 patients undergoing outpatient endoscopic examination during the period between January and December 2015. Were included patients with any esophageal alteration at the examination; greater than 18; of both genders; independent of the complaint or the reason for the examination, illness or drug use. Were excluded those with active bleeding during the examination and in use of anticoagulants. The variables gender, age, esophagitis and result of the urease test, were studied. For statistical analysis was used the Epi Info software 7.1.5.2. Results: Most of the samples consisted of women and the overall average age was 46.54±16.32 years. The presence of infection was balanced for gender: 1204 (12.56%) women and 952 (13.92%) men. Relating degree of esophagitis HP- and HP+ was observed that the type A was the most common (58.79%, n=1460); 604 (24.32%) had grade B; 334 (13.45%) grade C, and 85 (3.42%) grade D. In the relation between the grade of esophagitis with gender, esophagitis A was predominant in women and present in 929 (63.33%), followed by type B, 282 (46.68%), 136 C (40.71%) and D 30 (35.29%). In men 531 (36.36%) showed type A, 322 (53.31%) B, 198 (59.28%) C, and 55 (64.70%) D. Among the groups 40-50 and over 60 years there was a significant difference in whether have or not have HP+. Conclusion: There is no significant difference between HP infection and the different grades of esophagitis. PMID:27759772

  19. Catumaxomab for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas

    ClinicalTrials.gov

    2016-10-13

    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

  20. Do large hiatal hernias affect esophageal peristalsis?

    PubMed Central

    Roman, Sabine; Kahrilas, Peter J; Kia, Leila; Luger, Daniel; Soper, Nathaniel; Pandolfino, John E

    2013-01-01

    Background & Aim Large hiatal hernias can be associated with a shortened or tortuous esophagus. We hypothesized that these anatomic changes may alter esophageal pressure topography (EPT) measurements made during high-resolution manometry (HRM). Our aim was to compare EPT measures of esophageal motility in patients with large hiatal hernias to those of patients without hernia. Methods Among 2000 consecutive clinical EPT, we identified 90 patients with large (>5 cm) hiatal hernias on endoscopy and at least 7 evaluable swallows on EPT. Within the same database a control group without hernia was selected. EPT was analyzed for lower esophageal sphincter (LES) pressure, Distal Contractile Integral (DCI), contraction amplitude, Contractile Front Velocity (CFV) and Distal Latency time (DL). Esophageal length was measured on EPT from the distal border of upper esophageal sphincter to the proximal border of the LES. EPT diagnosis was based on the Chicago Classification. Results The manometry catheter was coiled in the hernia and did not traverse the crural diaphragm in 44 patients (49%) with large hernia. Patients with large hernias had lower average LES pressures, lower DCI, slower CFV and shorter DL than patients without hernia. They also exhibited a shorter mean esophageal length. However, the distribution of peristaltic abnormalities was not different in patients with and without large hernia. Conclusions Patients with large hernias had an alteration of EPT measurements as a consequence of the associated shortened esophagus. However, the distribution of peristaltic disorders was unaffected by the presence of hernia. PMID:22508779

  1. Diagnosis and management of esophageal achalasia.

    PubMed

    Stavropoulos, Stavros N; Friedel, David; Modayil, Rani; Parkman, Henry P

    2016-01-01

    Achalasia is a rare esophageal motility disorder that is usually idiopathic in origin. It is characterized by dysphagia, and patients often have chest pain, regurgitation, weight loss, and an abnormal barium radiograph showing esophageal dilation with narrowing at the gastroesophageal junction. Abnormal or absent esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) are typically seen on esophageal manometry. The advent of high resolution manometry (HRM) has allowed more precise diagnosis of achalasia, subtype designation, and differentiation from other esophageal motor disorders with an initial seminal publication in 2008 followed by further refinements of what has been termed the Chicago classification. Potential treatments include drugs, endoscopic botulinum toxin injection, balloon dilation, traditional surgery (usually laparoscopic Heller myotomy; LHM), and a novel, less invasive, natural orifice transluminal endoscopic surgery (NOTES) approach to Heller myotomy termed peroral endoscopic myotomy (POEM). The first human POEM was performed in 2008, with the first publication appearing in 2010 and evidence now rapidly accumulating showing POEM to be comparable to traditional surgery in terms of clinical success and radiologic and manometric post-therapy outcomes. This review discusses the diagnosis and management of achalasia with particular emphasis on the recent developments of HRM and POEM, which arguably represent the most important advances in the field since the advent of laparoscopic Heller myotomy in the 1990s. PMID:27625387

  2. Effect of total laryngectomy on esophageal motility

    SciTech Connect

    Hanks, J.B.; Fisher, S.R.; Meyers, W.C.; Christian, K.C.; Postlethwait, R.W.; Jones, R.S.

    1981-01-01

    Total laryngectomy for cancer can result in dysphagia and altered esophageal motility. Manometric changes in the upper esophageal sphincter (UES), and in proximal and distal esophageal function have been reported. However, most studies have failed to take into account radiation therapy and appropriate controls. We selected ten male patients (54.3 +/- 1.9 yr) for longitudinal manometric evaluation prior to laryngectomy then at two weeks and again six months later. No patient received preoperative radiation therapy, had a previous history of esophageal surgery, or developed a postoperative wound infection or fistula. Seven of ten patients had positive nodes and received 6,000-6,600 rads postoperative radiation therapy. Preoperatively 4 of 10 patients complained of dysphagia which did not significantly change following surgery and radiation. Two of three patients who did not complain of dysphagia preoperatively and received radiation postoperatively developed dysphagia. No patient without dysphagia preoperatively who received no radiation therapy developed symptoms. Our studies show that laryngectomy causes alterations in the UES resting and peak pressures but not in the proximal or distal esophagus, or the lower esophageal sphincter. These data also imply radiation therapy may be associated with progressive alterations in motility and symptomatology. Further study regarding the effects of radiation on esophageal motility and function are urged.

  3. Inflammatory response of esophageal epithelium in combined-type esophagitis in rats: a transcriptome analysis.

    PubMed

    Naito, Yuji; Kuroda, Masaaki; Uchiyama, Kazuhiko; Mizushima, Katsura; Akagiri, Satomi; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Yoshida, Norimasa; Ichikawa, Hiroshi; Yoshikawa, Toshikazu

    2006-11-01

    Recent studies have shown that esophageal mucosal inflammatory response is involved in the pathophysiology of gastro-esophageal reflux disease. The aim of the present study was to identify specific gene expression profiles of the esophageal mucosa in a rat model of combined-type chronic reflux esophagitis. Esophagogastroduodenal anastomosis was carried out in male Wistar rats by anastomosing the jejunum to the gastroesophageal junction under diethyl-ether inhalation anesthesia. Esophageal epithelial cells were obtained from esophagi of rats by laser capture microdissection. Preparation of cRNA and target hybridization were performed according to the Affymetrix GeneChip eukaryotic small sample target labeling assay protocol. The gene expression profile was evaluated by the rat toxicology U34 GeneChip. Array data analysis was carried out using Affymetrix GeneChip operating software, ingenuity pathway analysis software, and Gene Springs software. A comparison between esophagitis and sham-operated rats 2 weeks after the operation revealed that 368 probes (36%) were significantly affected, i.e. 185 probes were up-regulated, and 183 probes were down-regulated, both at levels of at least 1.5-fold in the esophagitis rats. Ingenuity signal analysis of 207 affected probes revealed the interleukin-6 signaling pathway as the most significantly affected caronical pathway. In addition, the expression of many genes associated with cytokine and transcription factor was enhanced in the esophagitis rats. This transcriptome approach provided insight into genes and putative genetic pathways thought to be affected by stimulation with gastroduodenal refluxates.

  4. Heme iron from meat and risk of adenocarcinoma of the esophagus and stomach.

    PubMed

    Ward, Mary H; Cross, Amanda J; Abnet, Christian C; Sinha, Rashmi; Markin, Rodney S; Weisenburger, Dennis D

    2012-03-01

    Iron can cause oxidative stress and DNA damage, and heme iron can catalyze endogenous formation of N-nitroso compounds, which are potent carcinogens. Dietary iron promotes esophageal cancer incidence in animal studies and has been identified as a growth factor for Helicobacter pylori, an established risk factor for stomach cancer. We conducted a population-based case-control study of adenocarcinoma of the esophagus (n=124) and stomach (n=154) and 449 controls in Nebraska. Heme iron and total iron intake were estimated from a food frequency questionnaire and databases of heme and total iron. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for known risk factors. Esophageal cancer was positively associated with higher intakes of heme iron (ORQ4 vs. Q1=3.04, 95% CI: 1.20-7.72; P trend=0.009) and total iron from meat sources (ORQ4 vs. Q1=2.67, 95% CI: 0.99-7.16; P trend=0.050). Risk of stomach cancer was elevated among those with higher intakes of heme iron (ORQ4 vs.Q1=1.99, 95% CI: 1.00-3.95; P trend=0.17) and total iron from meat (OR=2.26, 95% CI: 1.14-4.46; P trend=0.11). Iron intake from all dietary sources was not significantly associated with risk of either cancer. Our results suggest that high intakes of heme and iron from meat may be important dietary risk factors for esophageal and stomach cancer and may partly explain associations with red meat. PMID:22044848

  5. Protein profiling of alpha-fetoprotein producing gastric adenocarcinoma

    PubMed Central

    He, Liang; Ye, Fei; Qu, Linlin; Wang, Daguang; Cui, Miao; Wei, Chengguo; Xing, Yanpeng; Lee, Peng; Suo, Jian; Zhang, David Y.

    2016-01-01

    Alpha-fetoprotein (AFP) producing gastric adenocarcinoma is considered as a rare subtype of gastric adenocarcinoma. Compared with AFP non-producing gastric adenocarcinoma, our study and other previous studies showed that AFP producing gastric adenocarcinoma is more aggressive and prone to liver metastasis. Using the Protein Pathway Array, 11 of out of 286 proteins tested were found to be differentially expressed between AFP producing (n=32) and AFP non-producing (n=45) gastric adenocarcinoma tissues. In addition, the high level expression of XIAP and IGF-Irβ in gastric adenocarcinoma tissues was independent factors for poor prognosis in AFP producing gastric adenocarcinoma patients. A risk model based on the XIAP and IGF-Irβ expression levels can separate AFP producing gastric adenocarcinoma patients into 2 subgroups and each subgroup had a distinct set of signaling pathways involved. In conclusion, AFP producing gastric adenocarcinoma is a heterogeneous cancer with different clinical outcomes, biological behaviors and underlying molecular alterations. PMID:27057629

  6. Evaluation of gastric tube with esophageal thermister (Thermosump).

    PubMed

    Koyama, K; Ochiai, R; Takahashi, J; Takeda, J; Sekiguchi, H; Fukushima, K

    1992-07-01

    The accuracy and the feasibility of esophageal temperature measured by a new gastric tube. Thermosump, which is incorporated with a esophageal thermister, was evaluated in anesthetized dogs (n = 6) and men (n = 59). In dogs, esophageal temperature measured by Thermosump was correlated well with the temperatures measured by the conventional esophageal thermister, and also by the pulmonary artery catheter (r = 0.98, 0.98, respectively). In anesthetized men, correlation between esophageal temperature by Thermosump and rectal, or bladder temperature was good during surgery of extremities (r = 0.81, 0.80, respectively). But during abdominal surgery, correlation between esophageal and bladder temperature was relatively poor (r = 0.50). Insertion of the tube, and suction of gastric fluid through the tube were easy without any complication. This newly developed gastric tube with a esophageal thermister was safe, and useful for measuring esophageal temperature.

  7. [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

  8. Short-term neurodevelopmental outcome of babies operated on for low-risk esophageal atresia: a pilot study.

    PubMed

    Aite, L; Bevilacqua, F; Zaccara, A; Ravà, L; Valfrè, L; Conforti, A; Braguglia, A; Bagolan, P

    2014-01-01

    Data on the neurodevelopmental outcome of esophageal atresia (EA) survivors are scarce, controversial, and based on small samples. This is an observational prospective longitudinal study on a selected cohort of low-risk EA survivors. We considered a low-risk EA survivor a patient with the following characteristics: gestational age >32 weeks, no long gap, no genetic or chromosomic anomaly associated with neurodevelopmental delay, and no further major surgical congenital anomalies. Infants were evaluated with scales derived from the Bayley Scales of Infant and Toddler Development - 3rd Edition at 6 and 12 months, with a score of 100 considered normal for each scale. Analysis of variance was used to assess differences of cognitive and motor development. Linear regression was used to assess the impact of the following clinical and sociodemographic variables: gender, birthweight, gestational age, length of hospital stay, number of surgeries and number of esophageal dilatations during first hospitalization, days of mechanical ventilation, weight at follow up, number of surgeries and esophageal dilatations at follow up, parental age, educational level, and socioeconomic status. Thirty children form the object of the study. The mean (standard deviation [SD]) cognitive scale's score was 93.7 (7.5) and 98.2 (9.6) at 6 and 12 months, respectively (P < 0.05). The mean (SD) motor scale's score was 97.6 (9.3) and 98.0 (12.1) at 6 and 12 months, respectively (P = n.s.). Children with a body weight <5° percentile at 12 months showed a mean (SD) cognitive score significantly lower when compared with those with a body weight >5° percentile: 88.8 (6.3) and 100.5 (8.9), respectively. At 12 months, children with unemployed mothers had a mean (SD) motor score significantly lower when compared with those in the other socioeconomic classes: 87.7 (9.8) and 100.6 (12.4), respectively. In conclusion, parents of babies operated on for low-risk EA can be reassured about neurodevelopmental

  9. GERD—Barrett—Adenocarcinoma: Do We Have Suitable Prognostic and Predictive Molecular Markers?

    PubMed Central

    Illig, Romana; Klieser, Eckhard; Kiesslich, Tobias; Neureiter, Daniel

    2013-01-01

    Due to unfavorable lifestyle habits (unhealthy diet and tobacco abuse) the incidence of gastroesophageal reflux disease (GERD) in western countries is increasing. The GERD-Barrett-Adenocarcinoma sequence currently lacks well-defined diagnostic, progressive, predictive, and prognostic biomarkers (i) providing an appropriate screening method identifying the presence of the disease, (ii) estimating the risk of evolving cancer, that is, the progression from Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC), (iii) predicting the response to therapy, and (iv) indicating an overall survival—prognosis for EAC patients. Based on histomorphological findings, detailed screening and therapeutic guidelines have been elaborated, although epidemiological studies could not support the postulated increasing progression rates of GERD to BE and EAC. Additionally, proposed predictive and prognostic markers are rather heterogeneous by nature, lack substantial proofs, and currently do not allow stratification of GERD patients for progression, outcome, and therapeutic effectiveness in clinical practice. The aim of this paper is to discuss the current knowledge regarding the GERD-BE-EAC sequence mainly focusing on the disputable and ambiguous status of proposed biomarkers to identify promising and reliable markers in order to provide more detailed insights into pathophysiological mechanisms and thus to improve prognostic and predictive therapeutic approaches. PMID:23573078

  10. [Current status and perspectives of radiotherapy for esophageal cancer].

    PubMed

    Wu, S X; Wang, L H

    2016-09-23

    Esophageal cancer is one of the most common cancers in China. More than 80% of esophageal cancer patients are diagnosed at a late stage and are not eligible for surgery. Radiotherapy is one of the most important modalities in esophageal cancer treatment. Here we reviewed the advances in esophageal cancer radiotherapy and radiotherapy-based combined-modality therapy, such as optimization of radiation dose and target volume, application of precise radiotherapy technique and the integration of radiotherapy with chemotherapy and targeted therapy.

  11. Review of the Burden of Esophageal Cancer in Malaysia.

    PubMed

    Siti-Azrin, Ab Hamid; Wan-Nor-Asyikeen, Wan Adnan; Norsa'adah, Bachok

    2016-01-01

    Esophageal cancer is one of the top leading causes of cancer-related deaths in Malaysia. To date, neither the prevalence nor incidence of esophageal cancer nationally have been recorded. Esophageal cancer remains a major and lethal health problem even if it is not common in Malaysia. The late presentation of esophageal cancer makes it a difficult and challenging medical problem. Therefore, more governmental and non-governmental organizations of Malaysia should emphasize primary and secondary prevention strategies. PMID:27644604

  12. 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.

  13. Concomitant herpetic and eosinophilic esophagitis--a causality dilemma.

    PubMed

    Monsanto, P; Almeida, N; Cipriano, M A; Gouveia, H; Sofia, C

    2012-09-01

    Eosinophilic and herpetic esophagitis are listed as independent causes of dysphagia, especially in young adult males. However, herpetic esophagitis rarely affects immunocompetent individuals. We report the case of a young, not immunocompromised patient, admitted because of severe dysphagia secondary to herpes simplex virus esophagitis. After complete resolution, an endoscopic and histologic reevaluation established the diagnosis of eosinophilic esophagitis. The potential association between the two conditions is discussed.

  14. Interobserver Reproducibility of Diffusion-Weighted MRI in Monitoring Tumor Response to Neoadjuvant Therapy in Esophageal Cancer

    PubMed Central

    Kwee, Robert M.; Dik, Alexander K.; Sosef, Meindert N.; Berendsen, Ralph C. M.; Sassen, Sander; Lammering, Guido; Clarijs, Ruud; Oostenbrug, Liekele E.; Blom, Rachel L. G. M.; Vliegen, Roy F. A.

    2014-01-01

    Objective To investigate the reproducibility of diffusion-weighted magnetic resonance imaging (DW-MRI) in assessing tumor response early in the course of neoadjuvant chemoradiotherapy in patients with operable esophageal cancer. Methods Eleven male patients (mean age 54.8 years) with newly diagnosed esophageal cancer underwent DW-MRI before and 10 days after start of chemoradiotherapy. Reproducibility of apparent diffusion coefficient (ADC) measurements by manual (freehand) and semi-automated volumetric methods was assessed. Results Interobserver reproducibility for the assessment of mean tumor ADC by the manual measurement method was good, with an ICC of 0.69 (95% CI, 0.36 to 0.85; P = 0.001). Interobserver reproducibility for the assessment of mean tumor ADC by the semi-automated volumetric measurement method was very good, with an ICC of 0.96 (95% CI, 0.91 to 0.98; P<0.001). Conclusion Semi-automated volumetric ADC measurements have higher reproducibility than manual ADC measurements in assessing tumor response to chemoradiotherapy in patients with esophageal adenocarcinoma. PMID:24704912

  15. 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

  16. 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.

  17. 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

  18. CDX-2 Expression in Primary Lung Adenocarcinoma.

    PubMed

    Cowan, Morgan L; Li, Qing K; Illei, Peter B

    2016-01-01

    Adenocarcinoma with enteric differentiation is a rare subtype of lung adenocarcinoma that is recognized as a variant type of primary adenocarcinoma in the 2015 World Health Organization classification of lung tumors. Published immunohistochemistry studies show variable staining pattern for CDX-2 ranging from positivity in 71% of the cases to no staining. As little is known about CDX-2 expression in lung adenocarcinomas lacking histologic features of enteric differentiation, our aim was to determine the rate of CDX-2 positivity in non-enteric-type lung adenocarcinomas. We performed immunohistochemistry for CDX-2, CK7, CK20, TTF-1, napsin A, and p40 using 4-μm sections of a previously constructed tissue microarray containing 93 primary lung adenocarcinomas that lack morphologic evidence of enteric differentiation. The cohort included 22 well, 54 moderately, and 17 poorly differentiated tumors (55 female, 38 male; age range: 42 to 86, median: 64.5). All 93 tumors were strongly CK7 positive, whereas variable CK20 staining was seen in 4 tumors (1 strong, 1 moderate, and 2 focal). Both TTF-1 and napsin A were positive in 81 of 93 (87%) tumors with only 6 of 93 (6.5%) tumors negative for both the markers. Eleven tumors were CDX-2 positive (5 strong, 3 moderate, and 3 weak), all of which were also TTF-1 and napsin A positive and p40 negative. One CDX-2-positive tumor showed focal CK20 staining. Mutation studies for EGFR/K-ras/ALK were performed in four CDX-2-positive tumors and detected a K-ras mutation in one of them. CDX-2 positivity can be seen in a subset (12%) of lung adenocarcinoma. These tumors are CK7, TTF-1, and napsin A positive and p40 negative. Focal CK20 staining is only seen in rare cases. CDX-2 positivity should not be used as the only criteria to exclude lung origin. PMID:26469326

  19. CDX-2 Expression in Primary Lung Adenocarcinoma.

    PubMed

    Cowan, Morgan L; Li, Qing K; Illei, Peter B

    2016-01-01

    Adenocarcinoma with enteric differentiation is a rare subtype of lung adenocarcinoma that is recognized as a variant type of primary adenocarcinoma in the 2015 World Health Organization classification of lung tumors. Published immunohistochemistry studies show variable staining pattern for CDX-2 ranging from positivity in 71% of the cases to no staining. As little is known about CDX-2 expression in lung adenocarcinomas lacking histologic features of enteric differentiation, our aim was to determine the rate of CDX-2 positivity in non-enteric-type lung adenocarcinomas. We performed immunohistochemistry for CDX-2, CK7, CK20, TTF-1, napsin A, and p40 using 4-μm sections of a previously constructed tissue microarray containing 93 primary lung adenocarcinomas that lack morphologic evidence of enteric differentiation. The cohort included 22 well, 54 moderately, and 17 poorly differentiated tumors (55 female, 38 male; age range: 42 to 86, median: 64.5). All 93 tumors were strongly CK7 positive, whereas variable CK20 staining was seen in 4 tumors (1 strong, 1 moderate, and 2 focal). Both TTF-1 and napsin A were positive in 81 of 93 (87%) tumors with only 6 of 93 (6.5%) tumors negative for both the markers. Eleven tumors were CDX-2 positive (5 strong, 3 moderate, and 3 weak), all of which were also TTF-1 and napsin A positive and p40 negative. One CDX-2-positive tumor showed focal CK20 staining. Mutation studies for EGFR/K-ras/ALK were performed in four CDX-2-positive tumors and detected a K-ras mutation in one of them. CDX-2 positivity can be seen in a subset (12%) of lung adenocarcinoma. These tumors are CK7, TTF-1, and napsin A positive and p40 negative. Focal CK20 staining is only seen in rare cases. CDX-2 positivity should not be used as the only criteria to exclude lung origin.

  20. The significance of c-erb B-2 and p53 immunoreactivity in patients with adenocarcinoma of the esophagus.

    PubMed Central

    Duhaylongsod, F G; Gottfried, M R; Iglehart, J D; Vaughn, A L; Wolfe, W G

    1995-01-01

    OBJECTIVE: Studies in breast cancer suggest that p53 and c-erb B2 protein overexpression are predictive of outcome. The authors determined whether these molecular markers correlated with treatment response and survival in patients with adenocarcinoma of the esophagus and esophagogastric junction. METHOD: Immunostaining for p53 and c-erb B2 was performed on paraffin-embedded specimens from 42 patients with esophageal adenocarcinoma. All patients received neoadjuvant chemotherapy (cisplatin and fluorouracil [5-FU] x 3 cycles) and irradiation (4500 rads) followed by resection. RESULTS: In this cohort of patients, 79% (33/42) were positive for p53, and 43% (18/42) were positive for c-erb B2. p53 positivity correlated with residual disease in the resection specimen but not with disease-free survival. Although c-erb B2 negatively correlated with residual disease after resection and a 5-year survival of 10%, c-erb B2 positivity was associated with a 5-year actuarial survival of 60%. CONCLUSIONS: Although p53 protein overexpression is commonly observed in adenocarcinoma of the esophagus, its prognostic value appears limited. In contrast, c-erb B2 protein expression predicts a favorable response to therapy and improved survival. PMID:7794072

  1. 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

  2. [Acute necrotizing esophagitis (black esophagus) with secondary severe stenosis].

    PubMed

    Gómez, Álvaro A; Guerrero, Diego; Hani, Albis C; Cañadas, Raúl

    2015-01-01

    We report the case of a 67 years old patient with a history of diabetes mellitus, atrial fibrillation and chronic renal failure, who developed diabetic ketoacidosis and severe sepsis, later presenting an acute necrotizing esophagitis, and then a esophageal stenosis requiring treatment with self-expanding esophageal prosthesis with good clinical results. PMID:26802889

  3. Black esophagus (acute esophageal necrosis) after spinal anesthesia.

    PubMed

    Román Fernández, A; López Álvarez, A; Fossati Puertas, S; Areán González, I; Varela García, O; Viaño López, P M

    2014-01-01

    Acute esophagic necrosis or black esophagus is an uncommon clinical entity that owes its name to the endoscopic view of the necrotic esophageal mucosa. It is always related with a critical medical condition and usually has an ischemic etiology. We report the first case of acute esophageal necrosis after a spinal anesthetic for partial hip joint arthroplasty. We discuss the underlying pathophysiological mechanisms.

  4. [Esophageal reconstruction--using gastric tube instead of whole stomach].

    PubMed

    Chen, Keneng

    2014-09-01

    Stomach is the first choice for esophageal reconstruction following esophagectomy. In the earlier days, however, whole stomach pulling-up was the major surgery, which had some shortcomings. Recently, gastric tube has gained wide acceptance for esophageal reconstruction. This paper summarized the anatomical and physiological advantage of stomach, the disadvantage of whole stomach, and benefits of gastric tube for esophageal reconstruction.

  5. [Current status and prospect of treatment for esophageal cancer in the era of precision medicine].

    PubMed

    Guo, X T; He, J

    2016-09-23

    Esophageal cancer (EC) is one of the most common malignant tumors around the world and has a high incidence in China. Chinese EC patients account for more than 50% in the world. The pathological subtype of EC shows a geographic distribution. Adenocarcinoma is the main pathological type in western countries, while squamous cell carcinoma is the dominant subtype in China. Thus specific diagnosis and treatment of EC are needed for Chinese patients. Although early diagnosis, progress in surgery and comprehensive treatment of EC have made remarkable achievements in China in recent years, yet the prognosis for resectable EC patients remains poor, with a 5-year survival of 30%. In addition, as the level of treatment varies significantly in different regions and centers around China, the current status of treatment for EC needs further improvement. This article reviews the advances in the treatment for EC in recent years, analyzes the present problems, and explores the perspective of the progress in esophageal cancer treatment in the era of precision medicine.

  6. 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

  7. 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.

  8. Predictors of Survival in Esophageal Squamous Cell Carcinoma with Pathologic Major Response after Neoadjuvant Chemoradiation Therapy and Surgery: The Impact of Chemotherapy Protocols

    PubMed Central

    Li, Chia-Ying; Huang, Pei-Ming; Chu, Pei-Yi; Chen, Po-Ming; Lin, Mong-Wei; Kuo, Shuenn-Wen

    2016-01-01

    Tumor recurrence is an important problem threatening esophageal cancer patients after surgery, even when they achieve a pathologic major response (pMR) after neoadjuvant concurrent chemoradiation therapy (CCRT). The predictors related to overall survival and disease progression for these patients remain elusive. We aimed to identify factors that predict disease progression and overall survival in esophageal squamous cell carcinoma (SCC) patients who achieve a pMR after neoadjuvant CCRT followed by surgery. We conducted a retrospective study to analyze the factors influencing survival and disease progression after esophagectomy for esophageal cancer patients who had a major response to CCRT, which is defined by complete pathological response or microscopic residual disease without lymph node metastasis. From our study cohort, 285 patients underwent CCRT and subsequent esophagectomy; 171 (60%) of these patients achieved pMR. After excluding patients with lymph node metastases, incomplete clinical data, and adenocarcinomas, we enrolled 117 patients in this study. We found that the CCRT regimen was the only factor that influenced overall survival. The overall survival of the patients receiving taxane-incorporated CCRT was superior to that of patients receiving traditional cisplatin and 5-fluorouracil (PF) (P = 0.011). The CCRT regimen can significantly influence the clinical outcome of esophageal SCC patients who achieve pMR after neoadjuvant CCRT and esophagectomy. Incorporation of taxanes into cisplatin-based CCRT may be associated with prolonged survival. PMID:27777949

  9. Conservative surgical treatment of reflux esophagitis and esophageal stricture.

    PubMed Central

    Herrington, J L; Wright, R S; Edwards, W H; Sawyers, J L

    1975-01-01

    During a recent 3-year period, 17 consecutive patients were seen with advanced fibrotic esophageal strictures secondary to alkaline-acid-pepsin reflux. From detailed preoperative evaluations alone it was impossible to determine whether therapy should consist of excisional surgery, esophagogastroplasty or intra-operative dilatation with correction of reflux. Only at operation could the length, extent, degree and severity of the stricture be fully determined. Each of the 17 patients was treated by controlled dilatation, coupled with an antireflux procedure. This simplified approach proved successful on strictures thought preoperatively to be undilatable. It appears that this conservative approach is applicable to many advanced strictures and excisional and plastic procedures should be reserved for those cases that prove unyielding to intraoperative dilatation. The true appraisal of a reflux stricture and the choice of surgical procedure is best determined at the operating table. Images Fig. 5A. Fig. 5B. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. Fig. 12. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 17. Fig. 18. Fig. 19. Fig. 20. Fig. 21. PMID:1130874

  10. Vitamin E intake and Risk of Esophageal and Gastric Cancers in the NIH-AARP Diet and Health Study

    PubMed Central

    Carman, Sarah; Kamangar, Farin; Freedman, Neal D.; Wright, Margaret E.; Dawsey, Sanford M.; Dixon, L. Beth; Subar, Amy; Schatzkin, Arthur; Abnet, Christian C.

    2009-01-01

    We investigated the association of dietary α-tocopherol, γ-tocopherol, and supplemental vitamin E intake with the risk of esophageal squamous cell carcinoma (ESCC; n = 158), esophageal adenocarcinoma (EAC; n = 382), gastric cardia adenocarcinoma (GCA; n = 320), and gastric noncardia adenocarcinoma (GNCA; n = 327) in the NIH-AARP Diet and Health Study, a cohort of approximately 500,000 people. Data on dietary and supplemental vitamin E intake were collected using a validated questionnaire at baseline and were analyzed using Cox regression models. Intakes were analyzed as continuous variables and as quartiles. For dietary α-tocopherol, we found some evidence of association with decreased ESCC and increased EAC risk in the continuous analyses, with adjusted hazard ratios (HR) and 95% confidence intervals (CI) of 0.90 (0.81 – 0.99) and 1.05 (1.00 – 1.11), respectively, per 1.17 mg (half the interquartile range) increased intake. However, in quartile analyses, the p-value for trend was non-significant for both of these cancers. There was no association between dietary α-tocopherol and GCA or GNCA. We observed no statistically significant associations with γ-tocopherol. For supplemental vitamin E, the results were mainly null, except for a significantly lower risk of GNCA with higher doses of supplemental vitamin E. An increase of 71 mg/day (half the interquartile range) in supplemental vitamin E had an HR (95% CI) of 0.92 (0.85–1.00) and the p-value for trend in the quartile analyses was 0.015. PMID:19326432

  11. [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.

  12. Differences in esophageal cancer characteristics and survival between Chinese and Caucasian patients in the SEER database

    PubMed Central

    Lin, Min-Qiang; Li, Yue-Ping; Wu, San-Gang; Sun, Jia-Yuan; Lin, Huan-Xin; Zhang, Shi-Yang; He, Zhen-Yu

    2016-01-01

    Background To compare the clinicopathologic characteristics and survival of Chinese and Caucasian esophageal cancer (EC) patients residing in the US, using a population-based national registry (Surveillance Epidemiology and End Results [SEER]) database. Methods Patients with EC were identified from the SEER program from 1988 to 2012. Kaplan–Meier survival methods and Cox proportional hazards regression were performed. Results A total of 479 Chinese and 35,748 Caucasian EC patients were identified. Compared with Caucasian patients, the Chinese patients had a later year of diagnosis, remained married after EC was diagnosed, had esophageal squamous cell carcinomas (ESCCs) more frequently, had tumors located in the upper-third and middle-third of the esophagus more frequently, and fewer patients presented with poorly/undifferentiated EC and underwent cancer-directed surgery. In Chinese patients, the incidence of esophageal adenocarcinomas (EACs) increased from 1988 to 2012 (P=0.054), and the majority of EAC patients had tumors located in the lower thoracic esophagus. The overall survival (OS) was not significantly different between Chinese and Caucasian patients (P=0.767). However, Chinese patients with ESCC had a significantly better OS when compared to their Caucasian counterparts, whereas there was no significant difference in the OS between Chinese and Caucasian patients with EAC. Conclusion The presenting demographic features, tumor characteristics, and outcomes of EC patients differed between Chinese and Caucasian patients residing in the US. Chinese patients diagnosed with EAC tended to share similar clinical features with their Caucasian counterparts, and the Chinese patients with ESCC had better OS than their Caucasian counterparts. PMID:27799791

  13. 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

  14. The Tumor Microenvironment in Esophageal Cancer

    PubMed Central

    Lin, Eric W.; Karakasheva, Tatiana A.; Hicks, Philip D.; Bass, Adam J.; Rustgi, Anil K.

    2016-01-01

    Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment, which contains diverse cell populations, signaling factors, and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Anti-tumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immune checkpoints like programmed death-1 (PD-1). Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix (ECM) to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy. PMID:26923327

  15. Chronic Recurrent Esophageal Diverticulitis - A Rare Entity

    PubMed Central

    Manne, Ashish; Smith, Ioana; Hatchett, Jeremy; Juneau, Jeffrey; Kodali, Sudha; Malik, Talha A.; Weber, Fred H.

    2013-01-01

    In this report, we seek to shed light on a 44-year-old Caucasian male with a known history of an esophageal diverticulum, who was transferred to our facility after an upper endoscopy at an outside hospital suggested a purulent discharge emanating from the mouth of a mid-esophageal diverticulum. A barium swallow done at the outside institution had reportedly demonstrated an 8 cm long barium collection parallel to and anterolateral to the mid-and distal esophagus which terminated several centimeters proximal to the gastroesophageal junction. At our facility, antibiotics (piperacillin/tazobactam) were continued, and a double-contrast esophagram was performed. The presence of an unusual mid-esophageal diverticulum was confirmed. He clinically improved after a 3-day course of intravenous broad-spectrum antibiotics. No surgical or endoscopic repair was elected as the patient opted for continued medical management. While esophageal diverticula are not rare in humans, to our knowledge, this is the first report of development of esophageal diverticulitis in humans. We believe that antibiotic coverage in addition to dietary restriction is the logical mainstay of acute therapy. Optimal antibiotic coverage should likely include oral flora aerobes and anaerobes. Once symptoms resolve, diverticula may be managed expectantly.

  16. 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

  17. The Samarkand EAS installation and experimental results

    NASA Astrophysics Data System (ADS)

    Makhmudov, B. M.; Sirodzhev, N. S.; Alimov, T. A.; Aliev, N. A.; Kakhkharov, M. K.; Khamikov, N. Kh.; Vernov, S. N.; Khristiansen, G. B.

    1982-09-01

    The Samarkand University extensive-air-shower installation is briefly described, and experimental results obtained at this installation are discussed. It is shown that the spatial distribution of EAS Cerenkov emission at distances of 10-100 m from the EAS axis with respect to shape and absolute value given a purely protonic composition of the primary radiation can be made compatible with the scaling model only under the assumption of an anomalously sharp increase with energy of the cross section of the inelastic interactions of hadrons with atomic air nuclei. In addition, it is shown that the Xmax(E0) relationship (Xmax is the position of the maximum of an individual EAS) obtained at E0 exceeding 10 to the 17th eV on the basis of Yakutsk data does not contradict Samarkand data at E0 = 10 to the 16th eV.

  18. Risk factors for esophageal and gastric cancers in Shanxi Province, China: A case-control study

    PubMed Central

    GAO, Ying; HU, Nan; HAN, Xiao You; DING, Ti; GIFFEN, Carol; GOLDSTEIN, Alisa M; TAYLOR, Philip R

    2011-01-01

    Objective Smoking and alcohol consumption explain little of the risk for upper-gastrointestinal (UGI) cancer in China, where over half of all cases in the world occur. Methods We evaluated questionnaire-based risk factors for UGI cancers in a case-control study from Shanxi Province, China, including 600 esophageal squamous cell carcinomas (ESCC), 599 gastric cardia adenocarcinomas (GCA), 316 gastric noncardia adenocarcinomas (GNCA), and 1514 age- and gender-matched controls. Results Ever smoking and ever use of any alcohol were not associated with risk of UGI cancer; only modest associations were observed between ESCC risk and highest cumulative smoking exposure, as well as GNCA risk and beer drinking. While several associations were noted for socioeconomic and some dietary variables with one or two UGI cancers, the strongest and most consistent relations for all three individual UGI cancers were observed for consumption of scalding hot foods (risk increased 150% to 219% for daily vs never users) and fresh vegetables and fruits (risk decreased 48% to 70% for vegetables and 46% to 68% for fruits, respectively, for high vs low quartiles). Conclusion This study confirms the minor role of tobacco and alcohol in UGI cancers in this region, and highlights thermal damage as a leading etiologic factor. PMID:21846596

  19. Study of EAS neutron component temporal structure

    NASA Astrophysics Data System (ADS)

    Gromushkin, D. M.; Petrukhin, A. A.; Stenkin, Yu. V.; Yashin, I. I.

    2011-04-01

    The neutron component of Extensive Air Showers (EAS) carries information about the primary cosmic ray flux as well as about parameters of hadronic interactions at ultra-high energies. We present here the data obtained with the "Neutron" array which is a prototype of a novel type EAS array PRISMA (Stenkin, 2009). The prototype consists of 5 large area scintillator detectors (0.75 m2 each) placed in the corners and in the center of 5 m side square. The scintillator consisting of an alloy of ZnS(Ag) and 6LiF is shaped as a thin layer of grains covered with thin transparent plastic film.

  20. 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

  1. 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

  2. 47 CFR 11.41 - Participation in EAS.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Participation in EAS. 11.41 Section 11.41 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Organization § 11.41... sources, including NN, must have immediate access to an EAS Operating Handbook....

  3. 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

  4. Minimally invasive surgery for esophageal cancer.

    PubMed

    Santillan, Alfredo A; Farma, Jeffrey M; Meredith, Kenneth L; Shah, Nilay R; Kelley, Scott T

    2008-10-01

    Esophageal cancer represents a major public health problem worldwide. Several minimally invasive esophagectomy (MIE) techniques have been described and represent a safe alternative for the surgical management of esophageal cancer in selected centers with high volume and expertise in them. This article reviews the most recent and largest series evaluating MIE techniques. Recent larger series have shown MIE to be equivalent in postoperative morbidity and mortality rates to conventional surgery. MIE has been associated with less blood loss, less postoperative pain, and decreased intensive care unit and hospital length of stay compared with conventional surgery. Despite limited data, conventional surgery and MIE have shown no significant difference in survival, stage for stage. The myriad of MIE techniques complicates the debate of defining the optimal surgical approach for treating esophageal cancer. Randomized controlled trials comparing MIE with conventional open esophagectomy are needed to clarify the ideal procedure with the lowest postoperative morbidity, best quality of life after surgery, and long-term survival.

  5. Endoscopic options for early stage esophageal cancer

    PubMed Central

    Shah, Pari M.

    2015-01-01

    Surgery has traditionally been the preferred treatment for early stage esophageal cancer. Recent advances in endoscopic treatments have been shown to be effective and safe. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) allow endoscopists to remove small, superficial lesions, providing tumor specimen that can be examined for accurate pathologic tumor staging and assessment of adequacy of resection. Endoscopic ablation procedures, including photodynamic therapy (PDT) and radio frequency ablation (RFA), have also been shown to safely and effectively treat esophageal dysplasia and early stage neoplasia, with excellent long-term disease control. Both approaches are becoming more widely available around the world, and provide an alternative, safe, low risk strategy for treating early stage disease, making combined endoscopic therapy the recommended treatment of choice for early stage esophageal cancers. PMID:25642334

  6. Performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches in VQ codebook generation for image compression

    NASA Astrophysics Data System (ADS)

    Tsai, Jinn-Tsong; Chou, Ping-Yi; Chou, Jyh-Horng

    2015-11-01

    The aim of this study is to generate vector quantisation (VQ) codebooks by integrating principle component analysis (PCA) algorithm, Linde-Buzo-Gray (LBG) algorithm, and evolutionary algorithms (EAs). The EAs include genetic algorithm (GA), particle swarm optimisation (PSO), honey bee mating optimisation (HBMO), and firefly algorithm (FF). The study is to provide performance comparisons between PCA-EA-LBG and PCA-LBG-EA approaches. The PCA-EA-LBG approaches contain PCA-GA-LBG, PCA-PSO-LBG, PCA-HBMO-LBG, and PCA-FF-LBG, while the PCA-LBG-EA approaches contain PCA-LBG, PCA-LBG-GA, PCA-LBG-PSO, PCA-LBG-HBMO, and PCA-LBG-FF. All training vectors of test images are grouped according to PCA. The PCA-EA-LBG used the vectors grouped by PCA as initial individuals, and the best solution gained by the EAs was given for LBG to discover a codebook. The PCA-LBG approach is to use the PCA to select vectors as initial individuals for LBG to find a codebook. The PCA-LBG-EA used the final result of PCA-LBG as an initial individual for EAs to find a codebook. The search schemes in PCA-EA-LBG first used global search and then applied local search skill, while in PCA-LBG-EA first used local search and then employed global search skill. The results verify that the PCA-EA-LBG indeed gain superior results compared to the PCA-LBG-EA, because the PCA-EA-LBG explores a global area to find a solution, and then exploits a better one from the local area of the solution. Furthermore the proposed PCA-EA-LBG approaches in designing VQ codebooks outperform existing approaches shown in the literature.

  7. Spinal cord compression due to ethmoid adenocarcinoma.

    PubMed

    Johns, D R; Sweriduk, S T

    1987-10-15

    Adenocarcinoma of the ethmoid sinus is a rare tumor which has been epidemiologically linked to woodworking in the furniture industry. It has a low propensity to metastasize and has not been previously reported to cause spinal cord compression. A symptomatic epidural spinal cord compression was confirmed on magnetic resonance imaging (MRI) scan in a former furniture worker with widely disseminated metastases. The clinical features of ethmoid sinus adenocarcinoma and neoplastic spinal cord compression, and the comparative value of MRI scanning in the neuroradiologic diagnosis of spinal cord compression are reviewed.

  8. High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population.

    PubMed

    Ibiebele, Torukiri I; Hughes, Maria Celia; Pandeya, Nirmala; Zhao, Zhen; Montgomery, Grant; Hayward, Nick; Green, Adèle C; Whiteman, David C; Webb, Penelope M

    2011-02-01

    Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.

  9. 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.

  10. [Endoscopic ultrasonic diagnosis of esophageal cancer].

    PubMed

    Kouzu, T; Ogino, Y; Isono, K

    1986-08-01

    Endoscopic Ultrasonography (EUS) has been developed rapidly and is becoming a new routine examination of the digestive diseases. In this thesis, the usefulness of EUS with reference to the diagnosis of the depth and the margins of the cancer invasion and the metastatic lymph nodes is described. Furthermore, the judgment of the efficacy of the combined therapy including radiotherapy, chemotherapy and immunotherapy will be possible with EUS. The information from EUS is useful to determine the treatment plan of esophageal cancer. Therefore, EUS is expected to become a preoperative necessary examination of cases with esophageal cancer. PMID:3537360

  11. 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

  12. Esophageal web in Plummer-Vinson syndrome.

    PubMed

    Okamura, H; Tsutsumi, S; Inaki, S; Mori, T

    1988-09-01

    In Plummer-Vinson syndrome, esophagography often reveals a web at the anterior wall of the cervical esophagus. The pathogenesis of the esophageal web and the cause of dysphagia in this syndrome were investigated radiographically, endoscopically, manometrically, and histologically. It was considered that the web seen in the esophagogram may have been formed due to the restriction of dilation of the esophageal wall, which results from repetitive inflammation and the subsequent healing process. Dysphagia in this syndrome may be explained by a decrease in swallowing power. Iron deficiency anemia may play the main role in the above histological changes and the resulting decrease in swallowing power.

  13. 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...

  14. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., satellite, public switched telephone network, or any other source that uses the EAS protocol. (2) Valid..., either internally or externally, at least two minutes of audio or text messages. A decoder manufactured... messages which still have valid time periods must be stored for comparison with the incoming valid...

  15. 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... form to be used for analysis and documentation by HUD for projects and activities under subpart E....

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 47 CFR 11.33 - EAS Decoder.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... satisfied via an Intermediary Device, as specified in § 11.56(b), provided that all other requirements set...: (1) Inputs. Decoders must have the capability to receive at least two audio inputs from EAS monitoring assignments, and at least one data input. The data input(s) may be used to monitor...

  1. Distal Esophageal Duplication Cyst with Gastro-Esophageal Reflux Disease: A Rare Association and a Management Challenge.

    PubMed

    Jan, Iftikhar Ahmad; Al Nuaimi, Asma; Al Hamoudi, Basma; Al Naqbi, Khalid; Bilal, Mohammad

    2016-02-01

    Esophageal duplication cysts are rare congenital abnormalities of the foregut and may be associated with other conditions. Association of esophageal duplication with Gastro-Esophageal Reflux Disease (GERD) has not been reported in children. We are reporting a case of a 16 months baby who had antenatal diagnosis of diaphragmatic hernia. Postnatal CTchest, however, suggested a distal esophageal duplication cyst and a contrast esophagogram showed grade-IV GER. A thoracoscopy in another hospital excluded esophageal duplication at that time. Later, he presented with hematemesis in our department and was re-evaluated. Repeat CTconfirmed a persistent 2.5 x 1.3 cm cyst in distal esophagus. Upper GI endoscopy suggested grade-II esophagitis with a wide patent gastro-esophageal junction. The child was treated with left thoracotomy, excision of the duplication cyst and thoracic fundoplication. He had an uneventful post-operative recovery and is doing well at 6 months follow-up. PMID:26876405

  2. 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.

  3. PPI-responsive esophageal eosinophilia and eosinophilic esophagitis: More similarities than differences

    PubMed Central

    Eluri, Swathi; Dellon, Evan S.

    2015-01-01

    Purpose of review To discuss the clinical, endoscopic, and histologic features, pathogenesis, and disease mechanisms of proton pump inhibitor–responsive esophageal eosinophilia (PPI-REE), and to highlight similarities and differences with eosinophilic esophagitis (EoE). Recent findings PPI-REE is a condition in which patients have clinical and histologic findings similar to EoE, but achieve complete remission with proton pump inhibitor (PPI) treatment. More than one-third of patients who have esophageal symptoms associated with esophageal eosinophilia respond to PPI treatment. Emerging data elucidating the pathogenesis of PPI-REE have shown that Th2-related inflammatory factors such as IL-13, IL-5, eotaxin-3, and major basic protein (MBP) are elevated in PPI-REE, similar to EoE. PPI-REE also shares a genetic expression signature with EoE that reverses with PPI treatment. Mechanisms proposed to explain the PPI response include an acid-independent, anti-inflammatory action of PPIs and PPI-induced restoration of esophageal barrier function. Summary Multiple features of PPI-REE overlap extensively with EoE. This raises the question of whether PPI-REE is merely a subtype of EoE rather than an independent condition. This similarity may have future implications for algorithms informing evaluation and treatment of esophageal eosinophilia. PMID:26039722

  4. Intramedullary conus medullaris metastasis of periurethral adenocarcinoma.

    PubMed

    Ramakonar, H H; Thomas, A; Lind, C R P

    2011-04-01

    Intramedullary spinal cord metastasis to the conus medullaris is very rare. We report a 44-year-old woman with an intra-axial conus medullaris metastasis from periurethral adenocarcinoma. To our knowledge, this is the first report in the literature. We also discuss the clinical features, possible pathophysiological mechanisms and treatment options for intramedullary spinal cord metastasis to the conus medullaris.

  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. 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

  7. Preoperative therapy in locally advanced esophageal cancer

    PubMed Central

    Garg, Pankaj Kumar; Sharma, Jyoti; Jakhetiya, Ashish; Goel, Aakanksha; Gaur, Manish Kumar

    2016-01-01

    Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

  8. 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.

  9. 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

  10. 21 CFR 868.5650 - Esophageal obturator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Esophageal obturator. 868.5650 Section 868.5650 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... patient during emergency resuscitation by occluding (blocking) the esophagus, thereby permitting...

  11. 21 CFR 868.5650 - Esophageal obturator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Esophageal obturator. 868.5650 Section 868.5650 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... patient during emergency resuscitation by occluding (blocking) the esophagus, thereby permitting...

  12. Perception of Syllable Stress in Esophageal Speech.

    ERIC Educational Resources Information Center

    Walker, Christopher Niles; Morris, Hughlett L.

    1988-01-01

    Ten esophageal speakers and ten normal speakers produced repetitions of the disyllable /mama/ using five different conditions of syllable stress. Nine normal listeners judged both relative and absolute syllable stress. Reliable judgments were made of the syllable stress, and speakers were able to effect systematic changes in listener perceptions…

  13. Does surgery correct esophageal motor dysfunction in gastroesophageal reflux

    SciTech Connect

    Russell, C.O.; Pope, C.E.; Gannan, R.M.; Allen, F.D.; Velasco, N.; Hill, L.D.

    1981-09-01

    The high incidence of dysphagia in patients with symptomatic gastroesophageal reflux (GER) but no evidence of peptic stricture suggests esophageal motor dysfunction. Conventional methods for detecting dysfunction (radiologic and manometric examinations) often fail to detect abnormality in these patients. Radionuclide transit (RT), a new method for detecting esophageal motor dysfunction, was used to prospectively assess function in 29 patients with symptomatic GER uncomplicated by stricture before and three months after antireflux surgery (HILL). The preoperative incidence of dysphagia and esophageal dysfunction was 73% and 52%, respectively. During operation (Hill repair), intraoperative measurement of the lower esophageal sphincter pressure was performed and the LESP raised to levels between 45 and 55 mmHg. The preoperative lower esophageal sphincter pressure was raised from a mean of 8.6 mmHg, to mean of 18.5 mmHg after operation. No patient has free reflux after operation. Postoperative studies on 20 patients demonstrated persistence of all preoperative esophageal dysfunction despite loss of dysphagia. RT has demonstrated a disorder of esophageal motor function in 52% of patients with symptomatic GER that may be responsible for impaired esophageal clearance. This abnormality is not contraindication to surgery. The results indicate that construction of an effective barrier to reflex corrects symptoms of reflux, even in the presence of impaired esophageal transit. Radionuclide transit is a safe noninvasive test for assessment of esophageal function.

  14. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.

    PubMed

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni; Roslind, Anne; Giese, Nathalia; Horn, Thomas; Wøjdemann, Morten; Johansen, Julia S

    2012-12-01

    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic

  15. Esophageal Manometry in Patients with Chest Pain and Normal Coronary Arteriogram.

    PubMed

    Ferguson, S C; Hodges, K; Hersh, T; Jinich, H

    1981-02-01

    Evaluation of the esophagus is helpful in determining the source of chest pain. Eighteen per cent of 72 patients with a normal coronary angiogram had esophageal disease as a source of chest pain. Eight had diffuse esophageal spasm, four had reflux esophagitis and one had an esophageal ulcer. Five of eight patients with diffuse esophageal spasm had relief of symptoms with nitroglycerin. Despite normal coronary arteriogram and normal esophageal manometry 42 of 49 other patients had relief of chest pain with nitroglycerin.

  16. Assessment of epidermal growth factor receptor mutation/copy number and K-ras mutation in esophageal cancer

    PubMed Central

    Guo, Kang; Wang, Wu-Ping; Jiang, Tao; Wang, Ju-Zheng; Chen, Zhao; Li, Yong; Zhou, Yong-An; Li, Xiao-Fei

    2016-01-01

    Background The molecular status of epidermal growth factor receptor (EGFR) in esophageal cancer has not been well elucidated. The purpose of the study was to investigate the prevalence of EGFR and K-ras mutation, and EGFR gene copy number status as well as its association with clinicopathologic characteristics, and also to identify the prognostic value of EGFR gene copy number in esophageal cancer. Methods EGFR mutation in exon 19/exon 21 and K-ras mutation in codon 12/codon 13 were detected by real-time PCR method, while EGFR gene copy number status was analyzed by fluorescent in situ hybridization (FISH). EGFR gene amplification and high polysomy were defined as high EGFR gene copy number status (FISH-positive), and all else were defined as low EGFR gene copy number status (FISH-negative). The relationship between EGFR gene copy number status and clinicpathologic characteristics was analyzed. Kaplan-Meier method and Cox proportional hazards regression model were employed to evaluate the effects of EGFR gene copy number status on the patients’ survival. Results A total of 57 esophageal squamous cell carcinoma (ESCC) patients and 9 esophageal adenocarcinoma (EADC) patients were enrolled in the study. EGFR mutation was identified in one patient who was diagnosed as ESCC with stage IIIC disease. K-ras mutation was identified in one patient who was diagnosed as EADC. In all, 34 of 66 (51.5%) samples were detected as FISH-positive, which includes 30 ESCC and 4 EADC tumor samples. The correlation analysis showed that FISH-positive was significantly associated with the tumor stage (P=0.019) and lymph node metastasis (P=0.005) in esophageal cancer patients, and FISH-positive was also significantly associated with the tumor stage (P=0.007) and lymph node metastasis (P=0.008) in ESCC patients. Cox regression analysis showed that high EGFR gene copy number was not a significant predictor of a poor outcome for esophageal cancer patients (P=0.251) or for ESCC patients (P=0

  17. Characteristics and frequency of transient relaxations of the lower esophageal sphincter in patients with reflux esophagitis.

    PubMed

    Mittal, R K; McCallum, R W

    1988-09-01

    Electromyogram of the submental muscles, esophageal manometry, and pH studies were simultaneously performed in an unselected group of 12 patients with subjective and objective evidence of gastroesophageal reflux (GER) disease to determine the frequency of transient relaxation of the lower esophageal sphincter (LES) and mechanisms of GER. Findings from these patients were compared with data from 10 asymptomatic healthy volunteers. Recordings were obtained for 1 h in the fasting state and 3 h after a standard 850-kcal meal. Transient relaxation of the LES was the only mechanism of acid reflux in normal subjects and accounted for 73.0% of the episodes of acid reflux in patients with GER disease. In both normal subjects and patients with GER, a large number of transient relaxations were associated at their onset with an attenuated submental EMG complex, a small pharyngeal contraction, and an esophageal contraction. The incidences of these associated events were similar in the two study populations. The frequency of transient relaxation of the LES in patients with GER was identical to that of controls. The frequency did not differ even in 9 patients with GER disease who had endoscopic esophagitis. Thirty-six percent of transient relaxations in the normal subjects were accompanied by pH evidence of reflux, but in the GER patients with endoscopic esophagitis 65% of the transient LES relaxations resulted in a reflux event. Acid reflux at the moment of deep inspiration was the second most common mechanism of GER in our patients. Four patients who demonstrated this mechanism had hiatal hernias and more severe esophagitis than the rest of the group. Our findings confirm that transient relaxation of the LES is the major mechanism of GER in patients with reflux esophagitis. However, the similar frequency of this relaxation in GER patients and in healthy asymptomatic subjects suggests that factors other than transient LES relaxation play an important role in the pathogenesis of

  18. Two distinct etiologies of gastric cardia adenocarcinoma: interactions among pH, Helicobacter pylori, and bile acids.

    PubMed

    Mukaisho, Ken-Ichi; Nakayama, Takahisa; Hagiwara, Tadashi; Hattori, Takanori; Sugihara, Hiroyuki

    2015-01-01

    Gastric cancer can be classified as cardia and non-cardia subtypes according to the anatomic site. Although the gastric cancer incidence has decreased steadily in several countries over the past 50 years, the incidence of cardia cancers and esophageal adenocarcinoma (EAC) continue to increase. The etiological factors involved in the development of both cardia cancers and EACs are associated with high animal fat intake, which causes severe obesity. Central obesity plays roles in cardiac-type mucosa lengthening and partial hiatus hernia development. There are two distinct etiologies of cardia cancer subtypes: one associated with gastroesophageal reflux (GER), which predominantly occurs in patients without Helicobacter pylori (H. pylori) infection and resembles EAC, and the other associated with H. pylori atrophic gastritis, which resembles non-cardia cancer. The former can be developed in the environment of high volume duodenal content reflux, including bile acids and a higher acid production in H. pylori-negative patients. N-nitroso compounds, which are generated from the refluxate that includes a large volume of bile acids and are stabilized in the stomach (which has high levels of gastric acid), play a pivotal role in this carcinogenesis. The latter can be associated with the changing colonization of H. pylori from the distal to the proximal stomach with atrophic gastritis because a high concentration of soluble bile acids in an environment of low acid production is likely to act as a bactericide or chemorepellent for H. pylori in the distal stomach. The manuscript introduces new insights in causative factors of adenocarcinoma of the cardia about the role of bile acids in gastro-esophageal refluxate based upon robust evidences supporting interactions among pH, H. pylori, and bile acids. PMID:26029176

  19. Fungal Esophagitis in a Child with Insulin Dependent Diabetes Mellitus.

    PubMed

    Saeed, Anjum; Assiri, Asaad; Zaidi, Zafar; Alsheikh, Abdulmalik

    2016-08-01

    Esophagitis in children is not uncommon, mostly due to gastro-esophageal reflux. Other conditions like eosinophilic and infective esophagitis need to be elucidated in differential diagnoses. Fungal orCandida esophagitisusually occurs in high risk children who are immune-compromised, malnourished, on steroid therapy or have uncontrolled diabetes mellitus. An eleven-year girl presented with uncontrolled type I diabetes mellitus and recurrent epigastric pain with vomiting. Her oral intake was satisfactory. There was no dysphagia and odynophagia. Physical examination was normal with good oral hygiene. Failure in responding to conventional medications led to endoscopic evaluation, which revealed white patches and esophageal inflammation and diagnosed as fungal esophagitis on histopathology. Although infective esophagitis is encountered sporadically in pediatric age group, but it should always be considered in high risk individuals and when conventional medication fails to resolve the symptoms. PMID:27539771

  20. 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.

  1. Genes Regulating Epithelial Polarity Are Critical Suppressors of Esophageal Oncogenesis

    PubMed Central

    Li, Xiu-Min; Wang, Hui; Zhu, Li-Li; Zhao, Run-Zhen; Ji, Hong-Long

    2015-01-01

    Esophageal cancer is an aggressive disease featured by early lymphatic and hematogenous dissemination, and is the sixth leading cause of cancer-related deaths worldwide. The proper formation of apicobasal polarity is essential for normal epithelium physiology and tissue homeostasis, while loss of polarity is a hallmark of cancer development including esophageal oncogenesis. In this review, we summarized the stages of esophageal cancer development associated with the loss or deregulation of epithelial cell apicobasal polarity. Loss of epithelial apicobasal polarity exerts an indispensable role in the initiation of esophageal oncogenesis, tumor progression, and the advancement of tumors from benign to malignant. In particular, we reviewed the involvement of several critical genes, including Lkb1, claudin-4, claudin-7, Par3, Lgl1, E-cadherin, and the Scnn1 gene family. Understanding the role of apicobasal regulators may lead to new paradigms for treatment of esophageal tumors, including improvement of prognostication, early diagnosis, and individually tailored therapeutic interventions in esophageal oncology. PMID:26185530

  2. Thoracoscopic esophageal atresia repair made easy. An applicable trick.

    PubMed

    Hiradfar, Mehran; Shojaeian, Reza; Gharavi Fard, Mohammad; Joodi, Marjan; Sabzevari, Alireza; Nazarzade, Reza

    2013-03-01

    Thoracoscopic repair of esophageal atresia is becoming more popular but technical difficulties in handsewn anastomosis still remain challenging. This article presents an easy and applicable maneuver by passing the trans-esophageal tube before starting to suture in order to minimize the gap, reduce the tension over primary sutures and provide a better visualization of posterolateral parts of the anastomosis in thoracoscopic esophageal atresia repair. Using this maneuver makes tying easier and minimizes grasping and crushing damages to the anastomotic site.

  3. Adult-Onset Esophageal Crohn’s Disease

    PubMed Central

    Kasarala, George; Durrett, Sam

    2016-01-01

    Crohn’s disease (CD) is an idiopathic inflammatory bowel disease that can involve any part of the gastrointestinal tract. Esophageal involvement is rarely seen in adults, especially at the initial diagnosis of CD. Esophageal symptoms as primary manifestations of the disease are extremely rare. We report a case of a CD with esophageal involvement at the time of her initial diagnosis of CD. PMID:27761477

  4. 47 CFR 11.55 - EAS operation during a State or Local Area emergency.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false EAS operation during a State or Local Area... SYSTEM (EAS) Emergency Operations § 11.55 EAS operation during a State or Local Area emergency. (a) The EAS may be activated at the State and Local Area levels by EAS Participants at their discretion...

  5. Pembrolizumab and Palliative Radiation Therapy in Treating Patients With Metastatic Esophagus, Stomach, or Gastroesophageal Junction Cancer

    ClinicalTrials.gov

    2016-10-05

    Adenocarcinoma of the Gastroesophageal Junction; Gastric Adenocarcinoma; Gastric Squamous Cell Carcinoma; Metastatic Malignant Neoplasm in the Stomach; Stage IV Esophageal Adenocarcinoma; Stage IV Esophageal Squamous Cell Carcinoma

  6. 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

  7. 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

  8. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis.

    PubMed

    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; Rothenberg, M E

    2014-05-01

    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. Moreover, DSG1 deficiency induces transcriptional changes that partially overlap with the transcriptome of inflamed esophageal mucosa; notably, periostin (POSTN), 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 POSTN. PMID:24220297

  9. 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

  10. [A case of esophageal achalasia followed by Parkinson's disease].

    PubMed

    Mitani, Maki; Kawamoto, Kunihiko; Funakawa, Itaru; Jinnai, Kenji

    2005-08-01

    In 1992, a 63 year-old woman complained of dysphagia and chest pain, and was diagnosed with esophageal achalasia. Three years later, she developed resting tremor, cog-wheel rigidity, and retro-pulsion, and was diagnosed with Parkinson's disease and given appropriate medication. Several years later, intractable vomitting and aspiration pneumonia developed, and the lower esophageal sphincter was dilated using a pneumatic balloon dilator under gastroscopic guidance in 2004. That procedure improved her symptoms and the esophageal dilation was visualized on chest CT images. Herein, we report this rare case of esophageal achalasia followed by Parkinson's disease and discuss the relationship between the two diseases.

  11. 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

  12. 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

  13. 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.

  14. Treatment of primary adenocarcinoma of the cervix.

    PubMed

    Weiner, S; Wizenberg, M J

    1975-06-01

    Between 1956 and 1971, a total of 74 cases of adenocarcinoma of the cervix was treatedin the Division of Radiation Therapy of the University of Maryland Hospital. Radical radiation therapy was followed by routine surgery early in the study;after 1967, surgery was used only for radiation failure. The likelihood of local control and 5-year survival was not improved by the routine addition of surgery to radical radiation, although the incidence of serious complications was markedly elevated. The results of treatment of adenocarcinoma of the cervix by radiation therapy alone are not significantly different from those achieved with squamous cell carcinoma. Surgery should be used as a salvage procedure in case of failure, rather than on a routine basis. PMID:1148986

  15. Genetics and Biology of Pancreatic Ductal Adenocarcinoma.

    PubMed

    Dunne, Richard F; Hezel, Aram F

    2015-08-01

    Pancreatic ductal adenocarcinoma remains a clinical challenge. Thus far, enlightenment on the downstream activities of Kras, the tumor's unique metabolic needs, and how the stroma and immune system affect it have remained untranslated to the clinical practice. Given the numbers of diverse therapies in development and a growing knowledge about how to evaluate these systems preclinically and clinically, this is expected to change significantly and for the better over the next 5 years. PMID:26226899

  16. Predictors of Survival in Sinonasal Adenocarcinoma

    PubMed Central

    Chen, Michelle M.; Roman, Sanziana A.; Sosa, Julie A.; Judson, Benjamin L.

    2015-01-01

    Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15–0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26–0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis. PMID:26225303

  17. Comprehensive molecular profiling of lung adenocarcinoma

    PubMed Central

    2014-01-01

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. PMID:25079552

  18. Predictors of Survival in Sinonasal Adenocarcinoma.

    PubMed

    Chen, Michelle M; Roman, Sanziana A; Sosa, Julie A; Judson, Benjamin L

    2015-06-01

    Objectives To identify factors associated with disease-specific survival (DSS) in intestinal and nonintestinal sinonasal adenocarcinoma. Design Retrospective review. Setting Surveillance Epidemiology and End Results database. Participants Adult patients with sinonasal adenocarcinoma. Main Outcome Measures DSS. Results We identified 325 patients; of these, 300 had the nonintestinal type and 25 had intestinal type histologies. The 5-year DSS rates for patients who had no treatment, radiation (RT), surgery, and surgery and postoperative RT were 42.5, 46.1, 85.6, and 72.6%, respectively (log-rank test; p < 0.001). Black race, age ≥ 75 years, paranasal sinus involvement, and high grade were independently associated with decreased DSS. Compared with RT, surgery (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.15-0.77), and adjuvant RT (HR: 0.47; 95% CI, 0.26-0.86) were associated with improved DSS. Conclusions There is no difference in prognosis between intestinal and nonintestinal subtypes of sinonasal adenocarcinoma. Treatment with surgery alone or adjuvant RT is associated with a more favorable prognosis. PMID:26225303

  19. Phyiscal associated companion of E+A Galaxies

    NASA Astrophysics Data System (ADS)

    Yamauchi, Chisato; Goto, Tomotsugu; Yagi, Masafumi

    2005-08-01

    The subject of this proposal is to identify physically associated companions of E+A galaxies, and to obtain basic spectroscopic features of bright companions in order to understand the evolution of E+A system. E+A galaxies have been understood as post-starburst galaxies based on their strong Balmer absorption lines and the absence of [OII] or H(alpha) emission lines. Their origin has remained unknown for more than 20 years since E+A galaxies are very rare. To rectify the situation, Goto (2003,2005) has selected large & uniform E+A sample using the Sloan Digital Sky Survey (SDSS) data. Goto (2003) found that there is an excess in number of accompanying galaxies of E+As in the SDSS imaging data, and suggest that the origin of E+As is dynamical merger/interaction with companion galaxies. The merger/interaction origin scenario also implies that E+As can be progenitors of early-type galaxies and play important roles in galaxy evolution. The discussion of Goto (2003) was based on the imaging data. The accompanying galaxies are not spectroscopically observed in SDSS, and it is unknown which galaxy is the real companion of E+A. We therefore propose spectroscopic observation to identify physically associated companions, and to construct companion catalog without any contamination of fore/background overlapping galaxies. The correlation between properties of E+A and those of companions would give us great hints for understanding the evolution of E+A system, and set constraints on the theoretical models of E+A formation.

  20. Physically associated companion of E+A Galaxies - III

    NASA Astrophysics Data System (ADS)

    Yamauchi, Chisato; Goto, Tomotsugu; Yagi, Masafumi

    2007-02-01

    The subject of this proposal is to identify physically associated companions of E+A galaxies, and to obtain basic spectroscopic features of bright companions in order to understand the evolution of E+A system. E+A galaxies have been understood as post-starburst galaxies based on their strong Balmer absorption lines and the absence of [OII] or H(alpha) emission lines. Their origin has remained unknown for more than 20 years since E+A galaxies are very rare. To rectify the situation, Goto (2003,2005) has selected large & uniform E+A sample using the Sloan Digital Sky Survey (SDSS) data. Goto (2003) found that there is an excess in number of accompanying galaxies of E+As in the SDSS imaging data, and suggest that the origin of E+As is dynamical merger/interaction with companion galaxies. The merger/interaction origin scenario also implies that E+As can be progenitors of early-type galaxies and play important roles in galaxy evolution. The discussion of Goto (2003) was based on the imaging data. The accompanying galaxies are not spectroscopically observed in the SDSS, and therefore it is unknown which galaxy is a real companion of E+A. We therefore propose spectroscopic observation to identify physically associated companions, and to construct a companion catalog without any contamination of fore/background overlapping galaxies. The correlation between properties of E+A and those of companions would give us great hints for understanding the evolution of the E+A system, and set constraints on the theoretical models of the E+A formation.

  1. Peroral endoscopic myotomy for esophageal achalasia

    PubMed Central

    Inoue, Haruhiro; Ikeda, Haruo; Sato, Hiroki; Sato, Chiaki; Hokierti, Chananya

    2014-01-01

    Peroral endoscopic myotomy (POEM) is one of the alternative treatment for achalasia. Due to concept of natural orifice transluminal endoscopic surgery (NOTES), it becomes popular and widely accepted. With the endoluminal technique, submucosal tunnel was created followed by endoscopic myotomy. POEM is not only indicated in classical achalasia but also other abnormal esophageal motility disorders. Moreover, failures of endoscopic treatment or surgical attempted cases are not contraindicated for POEM. The second attempted POEM is also safe and technically feasible. Even though the legend of success of POEM is fruitful, the possible complications are very frightened. Good training and delicate practice will reduce rate of complications. This review provides a summary of current state-of-the-art of POEM, including indication equipments, technique and complications. This perfect procedure may become the treatment of choice of achalasia and some esophageal motility disorders in the near future. PMID:25333007

  2. Spontaneous enterogastric reflux gastritis and esophagitis.

    PubMed Central

    Gowen, G F

    1985-01-01

    Enterogastric reflux gastritis and esophagitis is best known after gastric resections and pyloroplasty but it also occurs spontaneously in the nonoperated patient. Forty-two patients are presented who meet the criteria for the diagnosis: constant burning epigastric pain, worse after meals, unrelieved by antacids and diet; endoscopic demonstration of a gastric bile pool; endoscopic biopsy proof of gastritis and esophagitis; and hypochlorhydria. Patients with mild and moderate stages of the disease can benefit from metoclopramide therapy which improves the gastric emptying mechanism. Of the surgical patients with intractable symptoms, 90% were women, 90% had marked hypochlorhydria, 83% had biliary disease, current or remote, and 50% had anemia. With vagotomy, antrectomy, and Roux-Y anastomosis 45-60 cm downstream, the clinical response has been most encouraging. PMID:3970596

  3. 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

  4. Early esophageal cancer screening in China.

    PubMed

    Gao, Qin-Yan; Fang, Jing-Yuan

    2015-12-01

    In China, the incidence of esophageal cancer (EC) and its related mortality are high. Screening strategies aiming at early diagnosis can improve the prognosis. Researches on detection of early EC, especially in China are reviewed. Compared to esophageal balloon cytology or routine endoscopy, chromoendoscopy with Lugol's staining and biopsy appears to be the gold standard for early EC diagnosis in China today. Narrow-band imaging endoscopy, Confocal Laser endomicroscopy and other novel diagnostic approaches are more and more widely used in developed urban areas, but cost and lack of essential training to the endoscopists have made their use limited in rural areas. No specific biomarkers or serum markers were strongly commended to be used in screening strategies currently, which need to be evaluated in future. Trials on organized screening have been proposed in some regions of china with high disease prevalence. Screening in these areas has been shown to be cost effective. PMID:26651250

  5. Current strategies in chemoradiation for esophageal cancer

    PubMed Central

    Lloyd, Shane

    2014-01-01

    Chemoradiotherapy (CRT) has an important role in the treatment of esophageal cancer in both the inoperable and the pre-operative settings. Pre-operative chemoradiation therapy is generally given to 41.4-50.4 Gy with platinum or paclitaxel based chemotherapy. The most common definitive dose in the U.S. is 50-50.4 Gy. New advances in CRT for esophageal cancer have come from looking for ways to minimize toxicity and maximize efficacy. Recent investigations for minimizing toxicity have focused advanced radiation techniques such as IMRT and proton therapy, have sought to further define normal tissue tolerances, and have examined the use of tighter fields with less elective clinical target volume coverage. Efforts to maximize efficacy have included the use of early positron emission tomography (PET) response directed therapy, molecularly targeted therapies, and the use of tumor markers that predict response. PMID:24982764

  6. Early esophageal cancer screening in China.

    PubMed

    Gao, Qin-Yan; Fang, Jing-Yuan

    2015-12-01

    In China, the incidence of esophageal cancer (EC) and its related mortality are high. Screening strategies aiming at early diagnosis can improve the prognosis. Researches on detection of early EC, especially in China are reviewed. Compared to esophageal balloon cytology or routine endoscopy, chromoendoscopy with Lugol's staining and biopsy appears to be the gold standard for early EC diagnosis in China today. Narrow-band imaging endoscopy, Confocal Laser endomicroscopy and other novel diagnostic approaches are more and more widely used in developed urban areas, but cost and lack of essential training to the endoscopists have made their use limited in rural areas. No specific biomarkers or serum markers were strongly commended to be used in screening strategies currently, which need to be evaluated in future. Trials on organized screening have been proposed in some regions of china with high disease prevalence. Screening in these areas has been shown to be cost effective.

  7. Metastatic lung adenocarcinoma to the bladder: A case report

    PubMed Central

    YE, HAI-JUN; MA, JIAN; LIU, YING-JIE; YE, XIAO-FEI; ZHANG, LI-WANG; LI, JIN-GE

    2015-01-01

    Urothelial cancer is the most frequently diagnosed type of malignant tumor in the bladder, of which primary adenocarcinoma accounts for a small percentage. Secondary malignancies, in particular metastatic adenocarcinoma from the lung, are exceedingly rare, with only six cases previously reported in the literature. The present study describes the case of a 71-year-old Chinese male patient with known lung cancer for >2 years, who was diagnosed with metastatic adenocarcinoma to the bladder. The histopathological characteristics and immunohistochemical features of the patient are reported. It was proposed that pathologists should consider the possibility of metastatic adenocarcinoma from the lung, rather than assume a diagnosis of primary adenocarcinoma of the bladder or direct invasion of adenocarcinoma from the surrounding organs. Furthermore, it is essential to determine the medical history of each patient and observe the immunohistochemical features of all tumors prior to diagnosis. PMID:26622730

  8. 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.

  9. Vesical clear cell adenocarcinoma arising from endometriosis: A mullerian tumor, indistinguishable from ovarian clear cell adenocarcinoma.

    PubMed

    Miller, Eirwen M; Sun, Ying; Richardson, Ingride; Frimer, Marina

    2016-11-01

    Endometriosis is associated with increased rates of ovarian, particularly clear cell, adenocarcinomas. Malignant transformation of ovarian endometriosis is most common but rare cases have been reported in the bladder, abdominal wall, diaphragm, and rectum. We present the case of a 44-year-old female with vesical clear cell adenocarcinoma arising in a background of endometriosis in the absence of other pelvic endometriosis. The malignancy was diagnosed on transurethral resection of bladder tumor and managed with radical surgery. Histology and immunohistochemical findings were consistent mullerian origin and indistinguishable from similar tumors arising in the female genital tract. Extrapolating from the gynecologic literature, the recommendation was made for adjuvant chemotherapy. Further studies are needed to clarify the optimal treatment paradigm for ovarian and bladder clear cell adenocarcinomas. PMID:27660815

  10. 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

  11. 47 CFR 11.44 - EAS message priorities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Messages; second, State Messages; and third, National Information Center (NIC) Messages. (c) Key EAS... distribution of Presidential Messages. NIC messages received from national networks which are not broadcast...

  12. Primary Adenocarcinoma of an Ileostomy in Crohn's Disease

    PubMed Central

    Prasad, Meena A.; Lo, Amy; Bellaguarda, Emanuelle; Strong, Scott; Hanauer, Stephen B.

    2016-01-01

    Although Crohn's disease has been associated with an increased risk of small bowel adenocarcinoma, primary adenocarcinoma arising from an ileostomy is a complication that has been rarely documented in Crohn's disease. Chronic small bowel inflammation may lead to development of malignancy through the dysplasia-carcinoma sequence. We report a case of a 61-year-old woman with Crohn's ileocolitis diagnosed with a primary adenocarcinoma at the ileostomy with metastases to the liver 47 years after proctocolectomy, and review the literature.

  13. [Minimally Invasive Treatment of Esophageal Benign Diseases].

    PubMed

    Inoue, Haruhiro

    2016-07-01

    As a minimally invasive treatment of esophageal achalasia per-oral endoscopic myotomy( POEM) was developed in 2008. More than 1,100 cases of achalasia-related diseases received POEM. Success rate of the procedure was more than 95%(Eckerdt score improvement 3 points and more). No serious( Clavian-Dindo classification III b and more) complication was experienced. These results suggest that POEM becomes a standard minimally invasive treatment for achalasia-related diseases. As an off-shoot of POEM submucosal tumor removal through submucosal tunnel (per-oral endoscopic tumor resection:POET) was developed and safely performed. Best indication of POET is less than 5 cm esophageal leiomyoma. A novel endoscopic treatment of gastroesophageal reflux disease (GERD) was developed. Anti-reflux mucosectomy( ARMS) is nearly circumferential mucosal reduction of gastric cardia mucosa. ARMS is performed in 56 consecutive cases of refractory GERD. No major complications were encountered and excellent clinical results. Best indication of ARMS is a refractory GERD without long sliding hernia. Longest follow-up case is more than 10 years. Minimally invasive treatments for esophageal benign diseases are currently performed by therapeutic endoscopy. PMID:27440038

  14. 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

  15. 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

  16. Lymphocytic Esophagitis: A Diagnosis of Increasing Frequency

    PubMed Central

    Cohen, Shirley; Saxena, Aditi; Waljee, Akbar; Piraka, Cyrus; Purdy, Julianne; Appelman, Henry; McKenna, Barbara; Elmunzer, B. Joseph; Singal, Amit G.

    2012-01-01

    Background Despite being found with increasing frequency on esophageal biopsies, the clinical significance of lymphocytic esophagitis (LE) remains poorly understood. Goals The primary aim of our study was to characterize the clinical presentation and natural history of LE among adult patients. Study We retrospectively reviewed records for all 81 adult patients at the University of Michigan Medical Center who had a histopathological diagnosis of LE between January 1998 and November 2009. Patient demographics, clinical history, laboratory data, and imaging results from the time of diagnosis were obtained through review of computerized medical records. A telephone survey was conducted to collect natural history data. Results The number of LE diagnoses increased over time, with 81.5% (n=66) of patients being diagnosed in the last three years. The most frequent symptoms at the time of presentation were dysphagia (n=54), chest/abdominal pain (n=36), and heartburn (n=38). The majority (58.6%) of patients reported improvement in their initial gastrointestinal symptoms – most commonly associated with initiation of a proton pump inhibitor. Upon follow-up, most patients reported a good quality of life and satisfaction with their current health status. Conclusions Lymphocytic esophagitis is a new clinical entity with an increasing incidence. LE appears to have a benign natural history, with most patients reporting an improvement in symptoms and satisfaction with their health-related quality of life. Prospective studies are needed to better characterize the natural history and potential treatments for this clinical entity. PMID:22751335

  17. Esophageal Stricture Prevention after Endoscopic Submucosal Dissection

    PubMed Central

    Jain, Deepanshu; Singhal, Shashideep

    2016-01-01

    Advances in diagnostic modalities and improvement in surveillance programs for Barrett esophagus has resulted in an increase in the incidence of superficial esophageal cancers (SECs). SEC, due to their limited metastatic potential, are amenable to non-invasive treatment modalities. Endoscopic ultrasound, endoscopic mucosal resection, and endoscopic submucosal dissection (ESD) are some of the new modalities that gastroenterologists have used over the last decade to diagnose and treat SEC. However, esophageal stricture (ES) is a very common complication and a major cause of morbidity post-ESD. In the past few years, there has been a tremendous effort to reduce the incidence of ES among patients undergoing ESD. Steroids have shown the most consistent results over time with minimal complications although the preferred mode of delivery is debatable, with both systemic and local therapy having pros and cons for specific subgroups of patients. Newer modalities such as esophageal stents, autologous cell sheet transplantation, polyglycolic acid, and tranilast have shown promising results but the depth of experience with these methods is still limited. We have summarized case reports, prospective single center studies, and randomized controlled trials describing the various methods intended to reduce the incidence of ES after ESD. Indications, techniques, outcomes, limitations, and reported complications are discussed. PMID:26949124

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

    PubMed

    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 ((188)Re)-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 (188)Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the (188)Re-liposome. The combination of EBRT and (188)Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with (188)Re-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 (188)Re-liposome into feces and urine. In conclusion, the combination of EBRT with (188)Re-liposome might be a potential treatment modality for esophageal cancer.

  19. ALK positivity on pleuroscopic pleural biopsy in lung adenocarcinoma.

    PubMed

    Vaidya, Preyas J; Kate, Arvind H; Mehta, Deval; Dhabar, Boman N; Chhajed, Prashant N

    2016-01-01

    Lung cancer is the leading cause of cancer deaths worldwide, and around 75% to 80% of lung cancers are detected in advanced stage. Multiple genetic mutations are identified and reported in adenocarcinoma of the lung. Various pulmonary samples can be tested for molecular mutations in lung cancer. However, feasibility of molecular profiling of pleuroscopic pleural biopsies in lung adenocarcinoma is not reported. We describe a case of advanced adenocarcinoma of lung with positive anaplastic lymphoma tyrosine kinase mutation on pleuroscopic pleural biopsy and improved with oral crizotinib. The current case highlights the feasibility of pleuroscopy.-guided pleural biopsies in molecular profiling of lung adenocarcinoma. PMID:27461706

  20. 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%.