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Sample records for normal esophageal epithelium

  1. Blood group H(O) antigen in normal, dysplastic and carcinomatous esophageal epithelium.

    PubMed

    Sato, E; Maruta, K; Yonezawa, S; Nakamura, T

    1984-03-01

    Variation of the binding Ulex europaeus agglutinin-I (Ulex-I), a lectin specific for blood group H(O) substance, was examined in normal, dysplastic and cancerous esophageal epithelium from 43 instances of carcinoma by means of the lectin- antilectin peroxidase-antiperoxidase method. The normal epithelium showed strong staining at the cell border, although the basal cells were entirely negative. In mild and moderate dysplasia, staining was negative, while in some cases of severe dysplasia positive staining was found in the basal cells. Most of the basal cells in carcinoma in situ revealed granular or diffuse positive staining in the cytoplasm. The results indicate that the loss of blood group H antigen occurs during carcinogenesis of the esophageal mucosa. Thus, Ulex-I may be a useful marker of cytoplasmic differentiation of the esophagus. PMID:6373474

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

    NASA Astrophysics Data System (ADS)

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

    2003-10-01

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

  3. Keratinization of the esophageal epithelium of domesticated mammals.

    PubMed

    Meyer, Wilfried; Schoennagel, Britta; Kacza, Johannes; Busche, Roger; Hornickel, Isabelle Nina; Hewicker-Trautwein, Marion; Schnapper, Anke

    2014-01-01

    We studied the esophageal epithelium for keratinization characteristics from samples of domesticated mammals of three nutrition groups (herbivores: horse, cattle, sheep; omnivores: pig, dog, rat; carnivores: cat) using histochemistry (keratins, disulfides), sulfur measurements, and cryo-SEM. Keratins were found in all esophageal layers of all species, except for the equine Stratum corneum. The positive reaction staining of Pan-keratin was remarkable, but decreased in intensity toward the outer layers, whereas in the pig and cat, staining was confined to the corneal layer. The herbivores revealed positive staining reactions in the upper Stratum spinosum, particularly in the sheep. Regarding single keratins, CK6 immunostating was found in most esophageal layers, but only weakly or negatively in the porcine and equine Stratum corneum. CK13 staining was restricted to the sheep and here was found in all layers. CK14 could be detected in the equine and feline Stratum basale, and upper vital layers of the dog and rat. CK17 appeared only in the Stratum spinosum and Stratum granulosum, but in all layers of the dog and cat. Disulfides reacted strongest in the Stratum corneum of the herbivores, as corroborated by the sulfur concentrations in the esophagus. Our study emphasized that keratins are very important for the mechanical stability of the epithelial cells and cell layers of the mammalian esophagus. The role of these keratins in the esophageal epithelia is of specific interest owing to the varying feed qualities and mechanical loads of different nutrition groups, which have to be countered. PMID:23948668

  4. Effect of heat stress on rabbit esophageal epithelium.

    PubMed

    Tobey, N A; Sikka, D; Marten, E; Caymaz-Bor, C; Hosseini, S S; Orlando, R C

    1999-06-01

    Hot beverages expose the esophageal epithelium to temperatures as high as 58 degrees C. To study the impact of such temperatures, rabbit esophageal epithelium was exposed to luminal heat or both luminal and serosal heat while mounted in Ussing chambers. Luminal heat, mimicking exposure to hot beverages, reduced potential difference (PD) and resistance (R) when applied at >/=49 degrees C and reduced short-circuit current (Isc) at >/=60 degrees C. At >/=60 degrees C, subepithelial blisters developed. Higher temperatures reduced R only moderately and reversibly. In contrast, the Isc declined sharply and irreversibly once threshold was reached. Luminal and serosal heat also reduced PD, Isc, and R, although the threshold for reduction in Isc was now similar to that for R. Additionally, luminal and serosal heat reduced Isc more than R for any given temperature and resulted in blisters at lower temperatures (50 degrees C) than luminal heat alone. The heat-induced decline in Isc was attributed in part to inactivation of Na-K-ATPase activity, although other transport systems could have been equally affected, and the decline in R to an increase in paracellular permeability. The latter effect on R also contributed to an increase in tissue sensitivity to luminal acid damage. Consumption of hot beverages exposes the esophagus to temperatures that can negatively impact epithelial structure and function. Impaired barrier function by heat increases the risk of esophageal damage by subsequent contact with (refluxed) gastric acid. These findings help explain in part the association between esophageal disease and consumption of hot beverages. PMID:10362635

  5. [Epithelium constitution for esophageal tissue engineering using electrospinning technology].

    PubMed

    Chen, Ling; Lv, Jingjing; Yu, Xuechan; Kang, Cheng; Zhu, Yabin

    2013-12-01

    The basement membrane (BM) is crucial in regulating the physical and biological activities of esophageal epithelial cells which attach to the underlying BM. In order to simulate the natural construction of BM, we prepared the fibrous scaffolds using biodegradable polylactide (PLA) and silk fibroin (SF) as the materials via electrospinning technology. BM's proteins containing collagen (IV), laminin, entactin and proteoglycan were extracted from porcine esophagus and coated on the eletrospun fibers. Morphology, mechanical strength, biodegradability and cytocompatibility of the coated and uncoated scaffolds were tested and evaluated using scanning electron micrography, mechanical test system, immunofluorescence assay and western blotting with CK14 as the primary antibody. The fibrous scaffold PLA or PLA/SF, generated from the present protocol had good formation and mechanical and biodegradable properties. After coating with BM's proteins, the scaffold could enhance the growth and differentiation of esophageal epithelial cells, which would contribute to remodel and regenerate the tissue engineered epithelium and further contribute to engineer the whole esophagus in future. PMID:24660627

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

    PubMed Central

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

    2013-01-01

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

  7. Immunohistochemistry of dysplasias and carcinomas of the esophageal epithelium.

    PubMed

    Hurlimann, J; Gardiol, D

    1989-06-01

    Two types of high grade dysplasia were associated with invasive carcinomas. The first, deeply localized, had a pagetoid appearance and a particular phenotype: the dysplastic cells had keratins of low molecular weight rarely present in the esophagus; keratins of stratified epithelia were absent. This dysplasia was probably the origin of undifferentiated invasive carcinoma with which it was often associated. The second type, transepithelial, extended through the entire thickness of the epithelium. The abnormal cells presented some differentiation and stained positive for keratins of stratified epithelia. This dysplasia was often associated with differentiated squamous cell carcinoma. An intermediate-type dysplasia shared some characteristics with both main types. Several types of dysplasia and several areas of differently differentiated carcinoma were often associated in the same case. The evolutional potential of the different dysplasias is not known. PMID:2476791

  8. Physicochemical basis for dilated intercellular spaces in non-erosive acid-damaged rabbit esophageal epithelium.

    PubMed

    Tobey, N A; Gambling, T M; Vanegas, X C; Carson, J L; Orlando, R C

    2008-01-01

    Dilated intercellular spaces (DIS) within esophageal epithelium (EE) is a histopathologic feature of non-erosive reflux disease and early lesion in acid-damaged rabbit EE associated with increased paracellular permeability. Its cause remains unknown, but the lesion's morphology suggests a significant fluid shift into the intercellular spaces (ICS). Since water follows osmotic forces and consequently ion movements, we explored the role of active (ion) transport and ion gradients in its pathogenesis. This was done by quantifying the effect of inhibited active transport and altered ion gradients on electrical resistance (R(T)) and ICS diameter in acid-exposed Ussing-chambered rabbit EE. Compared with normal Ringer, pH 7.5, 30 minutes of luminal HCl (100 mmol/L), pH 1.1, increased permeability (R(T): +5 +/- 4% vs-52 +/- 4%) and ICS diameter (0.25 +/- 0.01 microm vs 0.42 +/- 0.02 microm), but had no effect on cell morphology or diameter. Ouabain pretreatment significantly reduced active transport but had no effect on the acid-induced changes. However, negating the chloride gradient created by luminal HCl either by adding choline chloride, 100 mmol/L, serosally or by replacing luminal HCl, pH 1.1, with luminal H(2)SO(4), pH 1.1, prevented the development of DIS while maintaining the increase in permeability. DIS was also prevented in the presence of a 100 mmol/L (choline) chloride gradient by luminal exposure at neutral pH. DIS in HCl-damaged EE is caused by an H(+)-induced increase in epithelial permeability; this enables Cl(-) to diffuse along its gradient into the ICS, creating an osmotic force for water movement into and (hydrostatic) dilation of the ICS. PMID:18522636

  9. Transgenic overexpression of cdx1b induces metaplastic changes of gene expression in zebrafish esophageal squamous epithelium.

    PubMed

    Hu, Bo; Chen, Hao; Liu, Xiuping; Zhang, Chengjin; Cole, Gregory J; Lee, Ju-Ahng; Chen, Xiaoxin

    2013-06-01

    Cdx2 has been suggested to play an important role in Barrett's esophagus or intestinal metaplasia (IM) in the esophagus. To investigate whether transgenic overexpression of cdx1b, the functional equivalent of mammalian Cdx2 in zebrafish, may lead to IM of zebrafish esophageal squamous epithelium, a transgenic zebrafish system was developed by expressing cdx1b gene under the control of zebrafish keratin 5 promoter (krt5p). Gene expression in the esophageal squamous epithelium of wild-type and transgenic zebrafish was analyzed by Affymetrix microarray and confirmed by in situ hybridization. Morphology, mucin expression, cell proliferation, and apoptosis were analyzed by hematoxylin & eosin (HE) staining, Periodic acid Schiff (PAS) Alcian blue staining, proliferating cell nuclear antigen (PCNA) immunohistochemical staining, and TUNEL assay as well. cdx1b was found to be overexpressed in the nuclei of esophageal squamous epithelial cells of the transgenic zebrafish. Ectopic expression of cdx1b disturbed the development of this epithelium in larval zebrafish and induced metaplastic changes in gene expression in the esophageal squamous epithelial cells of adult zebrafish, that is, up-regulation of intestinal differentiation markers and down-regulation of squamous differentiation markers. However, cdx1b failed to induce histological IM, or to modulate cell proliferation and apoptosis in the squamous epithelium of adult transgenic zebrafish. PMID:23672288

  10. Promoting epithelium regeneration for esophageal tissue engineering through basement membrane reconstitution.

    PubMed

    Lv, Jingjing; Chen, Ling; Zhu, Yabin; Hou, Lei; Liu, Yuxin

    2014-04-01

    Scaffolds mimicking hierarchical features of native extracellular matrices may facilitate cell growth and anatomical tissue regeneration. In our previous study, esophageal basement membrane (BM) was shown to be composed of interwoven fibers with mean diameter of 66 24 nm (range 28-165 nm) and with abundant pores of unequal sizes. The main extracellular matrix (ECM) contents found in porcine esophageal BM were collagen IV, laminin, entactin, and proteoglycans. In this work, biodegradable polycaprolactone (PCL) and silk fibroin (SF) were spun with electrospinning technology, both individually and in combination, to fabricate fibrous scaffolds with diameters between 64 and 200 nm. The surface morphologies of PCL, PCL/SF, and SF scaffolds were observed under scanning electron microscopy. Their mechanical properties were tested and the cytocompatibility was evaluated in vitro via culture of primary epithelial cells (ECs). The SF or PCL/SF scaffold favorably promoted epithelial cell attachment and proliferation comparing with PCL scaffold. However, mitochondrial activity of epithelial cells was greatly promoted when major BM proteins were coated onto the electrospun scaffold to provide an ECM-like structure. Results from in vivo tests revealed that the electrospun scaffolds coated with BM protein possess good biocompatibility and capability to promote epithelium regeneration. PMID:24679268

  11. Activity of mitogen-activated protein kinases in the esophageal epithelium of patients with Barrett's esophagus.

    PubMed

    Chwiesko, A; Baniukiewicz, A; Semeniuk, J; Kaczmarski, M; Wasielica-Berger, J; Milewski, R; Dabrowski, A

    2015-01-01

    Barrett's esophagus (BE), a complication of gastroesophageal reflux disease, is associated with an increased risk of esophageal cancer. Mitogen-activated protein kinases may play an important role in the pathogenesis of this process. We aimed to evaluate mitogen-activated protein kinases activity in esophageal mucosa of patients with BE and find possible relationship between reflux type and BE. Twenty-four patients (mean age: 59 years) with gastroesophageal reflux disease symptoms and endoscopically suspected esophageal metaplasia (ESEM) were prospectively enrolled for testing by a multichannel intraluminal impedance monitoring along with a Bilitec 2000. Endoscopic biopsies were taken from methylene blue-positive pit patterns (sites suggesting specialized intestinal metaplasia [SIM]), from 2?cm above the Z-line and from cardial parts of the stomach. The biopsies were analyzed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 activity by Western blot. Seventeen ESEMs had histologically proven metaplasia: eight patients had SIM and nine had gastric-type epithelia (GE). Biliary reflux was more evident in SIM (P = 0.019) but not in GE (P = 0.019); non-biliary reflux was typical for GE (P = 0.005) but not for SIM (P = 0.04). Strong activations of ERK and p38 were found predominantly in SIM, but not in normal esophageal mucosa (NE) (P = 0.01 and P < 0.001 respectively). Strong signals for active JNK and p38 were detected in GE, but not in NE (P = 0.006 and P = 0.02 respectively). ERK activity was significantly higher than p38 activity in ESEM patients only with GE (P = 0.02). The strong activation of ERK, but not JNK is indicative of SIM. The presence of bile in gastroesophageal refluxate is predisposing to SIM, but not to GE in esophageal mucosa. PMID:24867362

  12. STUDIES OF NORMAL GENE EXPRESSION IN THE RAT NASAL EPITHELIUM USNG CDNA ARRAY TECHNOLOGY

    EPA Science Inventory


    Studies of Normal Gene Expression in the Rat Nasal Epithelium Using cDNA Array

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity .Gene expression data are being used increasingly for studies of such conditions. In or...

  13. NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

    EPA Science Inventory

    Abstract

    The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

  14. Mitogenic regulation of normal and malignant breast epithelium.

    PubMed Central

    Lippman, M. E.; Dickson, R. B.

    1989-01-01

    The multiple roles of both estrogenic and polypeptide regulators of mammary epithelial cell growth are reviewed in this article. Effects of both steroidal and peptide hormones are complex and involve multiple interactions with malignant cells and non-malignant host components. Initial carcinogenesis and progression of mammary epithelium to cancer probably require both proliferative stimuli (estrogen, polypeptide growth factors) and genetic damage. This condition may lead to qualitatively different hormonal responses (hormone-responsive cancer). Estrogens can be shown to induce growth-regulatory polypeptide growth factors and interact with them in hormone-dependent breast cancer. Progression of hormone-dependent (estrogen-responsive) breast cancer to hormone independence probably involves multiple mechanisms, including oncogene activation, loss of the estrogen receptor, or loss of hormone responsivity of other gene products. One direction for further therapies may be blockade of hormonal stimulation and interference with necessary activated or induced components of malignant progression such as oncogenes or polypeptide growth factor-receptor systems. PMID:2697981

  15. Esophagitis

    MedlinePLUS

    ... increase your risk of esophagitis: Alcohol use Cigarette smoking Surgery or radiation to the chest (for example, treatment for lung cancer) Taking certain medicines without drinking plenty of water. ...

  16. Relative ion permeability of normal and cystic fibrosis nasal epithelium.

    PubMed Central

    Knowles, M; Gatzy, J; Boucher, R

    1983-01-01

    The raised transepithelial electric potential difference (PD) across respiratory epithelia in cystic fibrosis (CF) has suggested an abnormality in ion permeation. We characterized this abnormality further by measuring in the nasal epithelia of CF and normal subjects the concentration-PD relationship for amiloride, an inhibitor of cell Na+ permeability, and PD responses to superfusion with solutions of different composition. Amiloride was more efficacious in the CF subjects but the ED50 was not different from that of normals (approximately 2 X 10(-6) M). Na+ replacement by choline induced effects similar to those of amiloride, i.e. a greater depolarization in CF subjects. A 10-fold increase in the K+ concentration of the perfusate induced a small (less than 10 mV) depolarization in both subject populations. When Cl- in the perfusate was replaced by gluconate or SO2-(4) the nasal PD of normal subjects hyperpolarized (lumen became more negative) by approximately 35 mV. A significantly smaller response (less than 17 mV) was induced in CF homozygotes but not in heterozygotes (38 mV). The smaller response of CF subjects appears to reflect an absolute decrease in luminal surface Cl- permeability because pretreatment with amiloride did not increase the response to Cl- free solution (7 mV). Accordingly, three abnormalities (decreased Cl- permeability, raised PD, greater amiloride efficacy) have been identified in CF respiratory epithelia. Whereas "excessive" active Na+ transport can account for these abnormalities and the dessication of airway surface liquid, it is possible that a lower lumenal cell membrane Cl- permeability and inhibition of a potential path of Cl- secretion can also explain the observations. PMID:6853720

  17. Infrared spectroscopic characteristics of normal and malignant colonic epithelium

    NASA Astrophysics Data System (ADS)

    Krupnik, Eduardo; Jackson, Michael; Bird, Ranjana P.; Smith, Ian C. P.; Mantsch, Henry H.

    1998-04-01

    IR spectroscopy is being widely used to study the biochemical changes associated with cancer. In particular, based upon the hypothesis that biochemical changes associated with cancer precede morphological manifestations of the disease, IR spectroscopy is being evaluated as a potential early diagnostic and prognostic tool. In the current study, IR spectroscopy was applied to the study of colon tissue from rats treated with the specific colon carcinogen azoxymethane, to determine whether tumor induction was associated with identifiable spectroscopic changes in the colon. Characteristic spectra were found for each layer of the colon. Spectra of normal-appearing mucosa and tumors form treated animals then compared to spectra of control mucosa. Differences between tumors and control mucosa were apparent, indicating changes in cellular biochemistry associated with tumor development. In particular, differences in absorptions attributed to nucleic acids were seen, indicating alterations in the structure of cellular DNA in malignant and carcinogen treated tissues. Interestingly, spectra of carcinogen treated rates exhibit characteristics intermediate between those of normal mucosa and tumors. Application of multivariate analysis allowed non-subjective classification of the spectra into three distinct classes with and accuracy of 86.7 percent. The separate classification of control and treated mucosa suggests that IR spectroscopy, when combined with the appropriate classifier, can indeed detect biochemical changes in tissue before physical manifestation of the disease process.

  18. Aspiration cytology of radiation-induced changes of normal breast epithelium

    SciTech Connect

    Bondeson, L.

    1987-05-01

    From a case illustrated, it appears that irradiation may induce changes in normal breast epithelium indistinguishable from malignancy by means of aspiration cytology. This fact must be considered in the choice of diagnostic methods for the evaluation of lesions in irradiated breast tissue.

  19. Brain-derived neurotrophic factor (BDNF) expression in normal and regenerating olfactory epithelium of Xenopus laevis.

    PubMed

    Frontera, Jimena Laura; Cervino, Ailen Soledad; Jungblut, Lucas David; Paz, Dante Agustn

    2015-03-01

    Olfactory epithelium has the capability to continuously regenerate olfactory receptor neurons throughout life. Adult neurogenesis results from proliferation and differentiation of neural stem cells, and consequently, olfactory neuroepithelium offers an excellent opportunity to study neural regeneration and the factors involved in the maintenance and regeneration of all their cell types. We analyzed the expression of BDNF in the olfactory system under normal physiological conditions as well as during a massive regeneration induced by chemical destruction of the olfactory epithelium in Xenopus laevis larvae. We described the expression and presence of BDNF in the olfactory epithelium and bulb. In normal physiological conditions, sustentacular (glial) cells and a few scattered basal (stem) cells express BDNF in the olfactory epithelium as well as the granular cells in the olfactory bulb. Moreover, during massive regeneration, we demonstrated a drastic increase in basal cells expressing BDNF as well as an increase in BDNF in the olfactory bulb and nerve. Together these results suggest an important role of BDNF in the maintenance and regeneration of the olfactory system. PMID:25488259

  20. Differential contextual responses of normal human breast epithelium to ionizing radiation in a mouse xenograft model.

    PubMed

    Coates, Philip J; Appleyard, M Virginia C L; Murray, Karen; Ackland, Caroline; Gardner, June; Brown, Douglas C; Adamson, Dougal J A; Jordan, Lee B; Purdie, Colin A; Munro, Alastair J; Wright, Eric G; Dewar, John A; Thompson, Alastair M

    2010-12-01

    Radiotherapy is a key treatment option for breast cancer, yet the molecular responses of normal human breast epithelial cells to ionizing radiation are unclear. A murine subcutaneous xenograft model was developed in which nonneoplastic human breast tissue was maintained with the preservation of normal tissue architecture, allowing us to study for the first time the radiation response of normal human breast tissue in situ. Ionizing radiation induced dose-dependent p53 stabilization and p53 phosphorylation, together with the induction of p21(CDKN1A) and apoptosis of normal breast epithelium. Although p53 was stabilized in both luminal and basal cells, induction of Ser392-phosphorylated p53 and p21 was higher in basal cells and varied along the length of the ductal system. Basal breast epithelial cells expressed ?Np63, which was unchanged on irradiation. Although stromal responses themselves were minimal, the response of normal breast epithelium to ionizing radiation differed according to the stromal setting. We also demonstrated a dose-dependent induction of ?-H2AX foci in epithelial cells that was similarly dependent on the stromal environment and differed between basal and luminal epithelial cells. The intrinsic differences between human mammary cell types in response to in vivo irradiation are consistent with clinical observation that therapeutic ionizing radiation is associated with the development of basal-type breast carcinomas. Furthermore, there may be clinically important stromal-epithelial interactions that influence DNA damage responses in the normal breast. These findings demonstrate highly complex responses of normal human breast epithelium following ionizing radiation exposure and emphasize the importance of studying whole-tissue effects rather than single-cell systems. PMID:21084272

  1. Herpetic esophagitis

    SciTech Connect

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

    1981-12-01

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

  2. Glycan profile of oviductal isthmus epithelium in normal and superovulated ewes.

    PubMed

    Desantis, Salvatore; Accogli, Gianluca; Silvestre, Fabio; Binetti, Francesco; Cox, Sharon Natasha; Roscino, Mariateresa; Caira, Michele; Lacalandra, Giovanni Michele

    2016-04-01

    Glycans of oviductal isthmus are implicated in sperm-isthmus interaction, sperm storage, survival, and capacitation. Isthmus morphology and glycoprotein production are controlled by sex steroids, which could be responsible for alterations of some reproductive events in the superovulated ewes (SE). In this study, the oviductal isthmus epithelium was evaluated in normal and in SE using morphologic and lectin histochemical analysis. The epithelium of normal isthmi was significantly taller in folds than in crypts, whereas it significantly decreased in the folds of SE. Nonciliated cells (NCs) from normal, showed apical blebs revealing apocrine secretory activity, which was missing in SE. The quantitative analysis of lectin staining revealed higher Con A, DBA, and PNA reactivity but lower affinity to KOH-sialidase- (Ks)WGA, GSA II, LTA, UEA I, SBA, GSA I-B4, RCA120, KsPNA, MAL II, SNA in control isthmi compared with superovulated ones. The NCs apical blebs showed terminal fucose (Fuc), N-acetylgalactosamine (GalNAc), galactose (Gal), lactosamine, and O- and N-sialoglycans. In normal isthmi, the luminal surface of NCs and ciliated cells expressed Fuc, highly mannosilated N-glycans terminating with lactosamine as well as O-glycans ending with N-acetylglucosamine (GlcNAc) and GalNAc. Moreover, NCs microvilli contained Gal and α2-3-linked sialic acids. In SE, the luminal surface lacked Gal and GalNAcα1, 3(LFucα1,2)Galβ1,3/4GlcNAcβ1, whereas it was enriched with Fuc in the folds and with α2-3sialo-mucins both in crypts and in folds. The apical surface showed additional O- and N-linked sialoglycans in NCs and αGal in the cilia, which expressed α2-6-linked sialic acid only in the folds. The cytoplasm of control NCs showed highly mannosilated N-glycans throughout the epithelium and GlcNAc in the folds. After superovulation treatment, NCs expressed cytoplasmic terminal Fuc, βGalNAc, lactosamine, α2-3-, and α2-6-linked sialic acids in the folds. The cytoplasm of normal ciliated cells cells displayed a binding pattern similar to normal NCs except for the absence of higly mannosilated N-glycans in the folds, which appeared in superovulated samples. This study demonstrates glycan zone-specific distribution along the isthmus epithelium that is influenced by the superovulation treatment. Whether an alteration in the glycan distribution is implicated in the low-rate fertilization after natural mating of the superovulated sheep remains to be addressed. PMID:26792378

  3. Expression of the BCL-2 protein in normal and dysplastic bronchial epithelium and in lung carcinomas.

    PubMed Central

    Walker, C.; Robertson, L.; Myskow, M.; Dixon, G.

    1995-01-01

    Although expression of the bcl-2 protein has been investigated in a number of non-haematological malignancies, little is known of its distribution in premalignant lesions. Expression of bcl-2 was investigated immunohistochemically in archival biopsies of normal (n = 8) and dysplastic bronchial epithelium (n = 56) and in 31 bronchial resection margins and their corresponding carcinomas. All dysplasias had lost the prominent basal staining pattern seen in histologically normal epithelium. Two were negative and six had occasional basal positive cells. In 37 cases up to 66% of the epithelial cells throughout the full epithelial thickness were bcl-2 positive with weak to moderate staining intensity. In 11 cases, all severe dysplasias, strong expression was observed in > 90% of the epithelial cells. Four patterns of bcl-2 expression in dysplasias were identified and an increasingly aberrant pattern of bcl-2 expression correlated with an increasing grade of dysplasia (Spearman's rank correlation, P < or = 0.0001). Sixty-five per cent of the carcinomas contained bcl-2-positive cells. Patients with non-small-cell lung carcinomas (n = 27) in which > 50% of the tumour cells were bcl-2 positive showed a survival advantage compared with those with 0-25% bcl-2-positive cells (P = 0.02). No correlation was found between p53 expression (Walker et al., 1994) and bcl-2 expression in dysplasias or carcinomas. Images Figure 1 Figure 2 PMID:7599047

  4. Specific Changes of Chromatin Structure in Nuclei of Normal Epithelium Adjacent to Laryngeal Squamous Cell Carcinoma

    PubMed Central

    Dreyer, Thomas; Knoblauch, Iris; Garner, David; Doudkine, Alexei; MacAulay, Calum; Palcic, Branko; Popella, Christian

    2000-01-01

    The aim of this study was to confirm the existence of specific nuclear texture feature alterations of histologically normal epithelial borders nearby invasive laryngeal cancer (NC). Paraffin sections of NC and of chronic inflammations unrelated to cancer (CI) were analysed for nuclear texture and for integrated optical density (IOD?index) and were compared to normal epithelium of patients without evidence of cancer (NE). Several discriminant functions based on nuclear texture features were trained to separate different subgroups. As the most important result, specific nuclear texture feature shifts were only found in NC with high?density lymphocytic stroma infiltrate (NC+). Classification of nuclei of NE versus NC+ was correct in 70%. The same classifier was correct in only 58% when nuclei of NE were classified versus CI. We also found lower values of IOD?Index within the NC+ group when compared to NE (p < 0:001). PMID:11153609

  5. p53 expression in normal and dysplastic bronchial epithelium and in lung carcinomas.

    PubMed Central

    Walker, C.; Robertson, L. J.; Myskow, M. W.; Pendleton, N.; Dixon, G. R.

    1994-01-01

    Bronchial epithelial dysplasia is thought to be a premalignant stage in the evolution of lung cancers. Using the CM-1 polyclonal antibody, we have examined the expression of the p53 protein in a larger series of bronchial dysplasias (n = 60) than hitherto investigated. The p53 protein was detected in 14% of mild, 25% of moderate and 59% of severe dysplasias; increased p53 expression correlated with the severity of dysplasia. p53-positive dysplasias had greater PCNA indices than p53-negative dysplasias. p53 expression in dysplastic tissues was compared with that in two groups of histologically normal epithelium: 14 bronchial biopsies from non-cancer patients of which all but one were negative and 32 bronchial margins from resected carcinomas, of which 17 showed infrequent solitary cells with p53-positive nuclei in predominantly basal locations scattered throughout the epithelium. These results for resection margins were confirmed by use of a second antibody, DO-1. Sixty-nine per cent of the corresponding carcinomas were p53 positive, but in 15 cases the p53 reactivity differed from resection margins. No correlation between p53 expression and any of the clinicopathological characteristics of these tumours was found. This study supports the observation that abnormal p53 expression may be an early but not obligatory event in malignant transformation in lung. Images Figure 1 Figure 2 PMID:7914423

  6. Corneal Epithelium Thickness Profile in 614 Normal Chinese Children Aged 7–15 Years Old

    PubMed Central

    Ma, Yingyan; He, Xiangui; Zhu, Xiaofeng; Lu, Lina; Zhu, Jianfeng; Zou, Haidong

    2016-01-01

    The purpose of the study is to describe the values and distribution of corneal epithelium thickness (CET) in normal Chinese school-aged children, and to explore associated factors with CET. CET maps were measured by Fourier-domain optical coherence tomography (FD-OCT) in normal Chinese children aged 7 to 15 years old from two randomly selected schools in Shanghai, China. Children with normal intraocular pressure were further examined for cycloplegic autorefraction, corneal curvature radius (CCR) and axial length. Central (2-mm diameter area), para-central (2- to 5-mm diameter area), and peripheral (5- to 6-mm diameter area) CET in the superior, superotemporal, temporal, inferotemporal, inferior, inferonasal, nasal, superonasal cornea; minimum, maximum, range, and standard deviation of CET within the 5-mm diameter area were recorded. The CET was thinner in the superior than in the inferior and was thinner in the temporal than in the nasal. The maximum CET was located in the inferior zone, and the minimum CET was in the superior zone. A thicker central CET was associated with male gender (p = 0.009) and older age (p = 0.037) but not with CCR (p = 0.061), axial length (p = 0.253), or refraction (p = 0.351) in the multiple regression analyses. CCR, age, and gender were correlated with para-central and peripheral CET. PMID:27004973

  7. Papillomavirus and c-myc antigen expression in normal and neoplastic cervical epithelium.

    PubMed Central

    Hughes, R G; Neill, W A; Norval, M

    1989-01-01

    Cervical punch biopsy specimens or brushings were collected from 33 patients with cervical human papilloma virus (HPV) infection, cervical intraepithelial neoplasia (CIN), or invasive cervical carcinoma, and from eight control patients with recent normal cervical cytology. Prostatic chippings obtained from six men with benign prostatic hypertrophy were used as further controls. Biopsy specimens and brushings were assayed by flow cytometry for c-myc oncogene antigen and papillomavirus antigen expression and rate of cell division (by measuring DNA content). Results obtained from analysis of specimens and brushings were similar in terms of c-myc antigen and total DNA content, but when the percentages of nuclei from biopsy and brush specimens staining positively with antibody to papilloma viral antigens were compared, brush specimens gave consistently higher percentages than biopsy specimens. More specimens from normal epithelium were c-myc antigen positive (five of eight, (63%) than specimens from CIN II or III (two of 10, 20%), or invasive carcinoma (0%). No association was found between c-myc antigen expression and cell division. HPV antigen positive specimens were found to contain more dividing cells than negative specimens. PMID:2537854

  8. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    SciTech Connect

    Warren, Samantha; Partridge, Mike; Carrington, Rhys; Hurt, Chris; Crosby, Thomas; Hawkins, Maria A.

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  9. Gene expression abnormalities in histologically normal breast epithelium from patients with luminal type of breast cancer.

    PubMed

    Zubor, Pavol; Hatok, Jozef; Moricova, Petra; Kajo, Karol; Kapustova, Ivana; Mendelova, Andrea; Racay, Peter; Danko, Jan

    2015-05-01

    The gene expression profile of breast cancer has been described as a great breakthrough on the way to comprehend differences in cancer origin, behavior and therapy. However, gene expression profile in histologically normal epithelium (HNEpi) which could harbor genetic abnormalities predisposing breast tissue to develop malignancy was minor scope for scientists in the past. Thus, we aimed to analyze gene expressions in HNEpi and breast cancer tissue (BCTis) in order to establish its value as potential diagnostic marker for cancer development. We evaluated a panel of disease-specific genes in luminal type (A/B) of breast cancer and tumor surrounding HNEpi by qRT-PCR Array in 32 microdissected samples. There was 20.2 and 2.4% deregulation rate in genes with at least 2-fold or 5-fold over-expression between luminal (A/B) type breast carcinomas and tumor surrounding HNEpi, respectively. The high-grade luminal carcinomas showed higher number of deregulated genes compared to low-grade cases (50.6 vs. 23.8% with at least 2-fold deregulation rate). The main overexpressed genes in HNEpi were KLK5, SCGB1D2, GSN, EGFR and NGFR. The significant differences in gene expression between BCTis and HNEpi samples were revealed for BAG1, C3, CCNA2, CD44, FGF1, FOSL1, ID2, IL6R, NGFB, NGFR, PAPPA, PLAU, SERPINB5, THBS1 and TP53 gene (p < 0.05) and BCL2L2, CTSB, ITGB4, JUN, KIT, KLF5, SCGB1D2, SCGB2A1, SERPINE1 (p < 0.01), and EGFR, GABRP, GSN, MAP2K7 and THBS2 (p < 0.001), and GSN, KLK5 (p < 0.0001). The ontological gene analyses revealed high deregulations in gene group directly associated with breast cancer prognosis and origin. PMID:25407308

  10. DNA synthesis, cell proliferation index in normal and abnormal gallbladder epithelium.

    PubMed

    Lamote, J; Willems, G

    1997-09-15

    The observation of mitotic figures in the epithelium of the normal gallbladder is exceptional because cell renewal is occurring at a very slow rate. It is only after using 3H-thymidine and autoradiography to observe the cells in DNA synthesis that evidence of a significant epithelial cell replication has been provided. Because numerous mitotic figures and increased 3H-thymidine uptake have been observed after intraluminal introduction of foreign bodies or after ligation of the common bile duct in animals, mechanical distension has been supposed to represent an important trigger factor of cell proliferation in this hollow organ. An increased epithelial cell renewal was also observed in human gallbladders of patients with a complete obstruction of the common bile duct causing the distension. However, the absence of correlation between the degree of gallbladder distension and the proliferative response was suggesting that factors other than distension could be involved. In studies on experimental lithiasis cell proliferation appeared to be enhanced in the gallbladder epithelium of mice fed on a cholesterol-cholic acid-rich lithogenic diet. The fact that the increase in proliferative activity was preceding the formation of gallstones was another indication that factors other than mechanical stimulation by stretching or by the stones may stimulate cell renewal in this organ. Factors in the bile of animals receiving a lithogenic diet could be involved which might cause cellular death and, hence, a regenerative reaction. Direct mitogenic effect of an unknown factor in the bile of these animals is an alternative possibility. On the other hand the stimulating effect of postprandial hormones on gallbladder cell renewal suggested by the observation of a DNA synthesis peak after feeding has been established. Synthetic cholecystokinin analogues have been shown to increase the proliferative activity and to induce epithelial hyperplasia in this organ. In one recent study using fundusectomy to increase the serum gastrin levels, a significant proliferative stimulation in the gallbladder was also observed. In human gallbladder mitotic activity in gallbladders with gallstones in much higher than in the controls. No correlation between stone number, weight or volume and the proliferative activity was put in evidence, whereas cell renewal appeared to be more influenced by the composition of the stones than by their physical presence. Epithelial DNA synthesis activity was, namely, much higher in gallbladders with cholesterol stones than in those with pigment stones. Whether increased cell turnover and, hence, cellular shedding into the lumen could represent a nucleating factor for cholesterol stones is an attractive working hypothesis. Considering the very high frequency of gallstones in man and also the frequent association of gallbladder cancer and lithiasis, further studies on mitotic activity in this organ are required. In conclusion, data from animal experiments and in vitro studies on human gallbladders indicate that gallbladder epithelial cell proliferation may be influenced by several mechanical, chemical and hormonal factors. The list of these factors is still incomplete while their possible role in gallbladder disease is a fascinating exploration field for future research. PMID:9330349

  11. Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium.

    PubMed

    Ortega-Martnez, Marta; Rodrguez-Flores, Laura E; de-la-Garza-Gonzlez, Carlos; Ancer-Rodrguez, Jess; Jaramillo-Rangel, Gilberto

    2015-11-01

    Regeneration of the lung airway epithelium after injury has been extensively studied. In contrast, analysis of its turnover in healthy adulthood has received little attention. In the classical view, this epithelium is maintained in the steady-state by the infrequent proliferation of basal or Clara cells. The intermediate filament protein nestin was initially identified as a marker for neural stem cells, but its expression has also been detected in other stem cells. Lungs from CD1 mice at the age of 2, 6, 12, 18 or 24 months were fixed in neutral-buffered formalin and paraffin-embedded. Nestin expression was examined by an immunohistochemical peroxidase-based method. Nestin-positive cells were detected in perivascular areas and in connective tissue that were in close proximity of the airway epithelium. Also, nestin-positive cells were found among the cells lining the airway epithelium. These findings suggest that nestin-positive stem cells circulate in the bloodstream, transmigrate through blood vessels and localize in the lung airway epithelium to participate in its turnover. We previously reported the existence of similar cells able to differentiate into lung chondrocytes. Thus, the stem cell reported here might be a bone marrow-derived mesenchymal stem cell (BMDMSC) able to generate several types of lung tissues. In conclusion, our findings indicate that there exist a BMDMSC in healthy adulthood that participates in the turnover of the lung airway epithelium. These findings may improve our knowledge about the lung stem cell biology and also provide novel approaches to therapy for devastating pulmonary diseases. PMID:26257389

  12. Detection of a novel stem cell probably involved in normal turnover of the lung airway epithelium

    PubMed Central

    Ortega-Martnez, Marta; Rodrguez-Flores, Laura E; de-la-Garza-Gonzlez, Carlos; Ancer-Rodrguez, Jess; Jaramillo-Rangel, Gilberto

    2015-01-01

    Regeneration of the lung airway epithelium after injury has been extensively studied. In contrast, analysis of its turnover in healthy adulthood has received little attention. In the classical view, this epithelium is maintained in the steady-state by the infrequent proliferation of basal or Clara cells. The intermediate filament protein nestin was initially identified as a marker for neural stem cells, but its expression has also been detected in other stem cells. Lungs from CD1 mice at the age of 2, 6, 12, 18 or 24months were fixed in neutral-buffered formalin and paraffin-embedded. Nestin expression was examined by an immunohistochemical peroxidase-based method. Nestin-positive cells were detected in perivascular areas and in connective tissue that were in close proximity of the airway epithelium. Also, nestin-positive cells were found among the cells lining the airway epithelium. These findings suggest that nestin-positive stem cells circulate in the bloodstream, transmigrate through blood vessels and localize in the lung airway epithelium to participate in its turnover. We previously reported the existence of similar cells able to differentiate into lung chondrocytes. Thus, the stem cell reported here might be a bone marrow-derived mesenchymal stem cell (BMDMSC) able to generate several types of lung tissues. In conclusion, our findings indicate that there exist a BMDMSC in healthy adulthood that participates in the turnover of the lung airway epithelium. These findings may improve our knowledge about the lung stem cell biology and also provide novel approaches to therapy for devastating pulmonary diseases. PMID:26257389

  13. A comparative Analysis by SAGE of Gene Expression Profiles of Esophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma

    PubMed Central

    van Baal, Jantine W. P. M.; Milana, Francesco; Rygiel, Agnieszka M.; Sondermeijer, Carine M. T.; Spek, C. Arnold; Bergman, Jacques J. G. H. M.; Peppelenbosch, Maikel P.; Krishnadath, Kausilia K.

    2008-01-01

    Esophageal adenocarcinoma (EA) and esophageal squamous cell carcinoma (ESCC) are the two main types of esophageal cancer. Despite extensive research the exact molecular basis of these cancers is unclear. Therefore we evaluated the transcriptome of EA in comparison to non-dysplastic Barretts esophagus (BE), the metaplastic epithelium that predisposes for EA, and compared the transcriptome of ESCC to normal esophageal squamous epithelium. For obtaining the transcriptomes tissue biopsies were used and serial analysis of gene expression (SAGE) was applied. Validation of results by RT-PCR and immunoblotting was performed using tissues of an additional 23 EA and ESCC patients. Over 58,000 tags were sequenced. Between EA and BE 1013, and between ESCC and normal squamous epithelium 1235 tags were significantly differentially expressed (p < 0.05). The most up-regulated genes in EA compared to BE were SRY-box 4 and Lipocalin2, whereas the most down-regulated genes in EA were Trefoil factors and Annexin A10. The most up-regulated genes in ESCC compared to normal squamous epithelium were BMP4, E-Cadherin and TFF3. The results could suggest that the BE expression profile is closer related to normal squamous esophagus then to EA. In addition, several uniquely expressed genes are identified. PMID:18219111

  14. Next-generation transcriptome sequencing of the premenopausal breast epithelium using specimens from a normal human breast tissue bank

    PubMed Central

    2014-01-01

    Introduction Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. In order to provide the specimens that will facilitate such an understanding, The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established. The KTB is, to our knowledge, the only biorepository in the world prospectively established to collect normal, healthy breast tissue from volunteer donors. As a first initiative toward a molecular understanding of the biology and developmental genetics of the normal mammary gland, the effect of the menstrual cycle and hormonal contraceptives on DNA expression in the normal breast epithelium was examined. Methods Using normal breast tissue from 20 premenopausal donors to KTB, the changes in the mRNA of the normal breast epithelium as a function of phase of the menstrual cycle and hormonal contraception were assayed using next-generation whole transcriptome sequencing (RNA-Seq). Results In total, 255 genes representing 1.4% of all genes were deemed to have statistically significant differential expression between the two phases of the menstrual cycle. The overwhelming majority (221; 87%) of the genes have higher expression during the luteal phase. These data provide important insights into the processes occurring during each phase of the menstrual cycle. There was only a single gene significantly differentially expressed when comparing the epithelium of women using hormonal contraception to those in the luteal phase. Conclusions We have taken advantage of a unique research resource, the KTB, to complete the first-ever next-generation transcriptome sequencing of the epithelial compartment of 20 normal human breast specimens. This work has produced a comprehensive catalog of the differences in the expression of protein-coding genes as a function of the phase of the menstrual cycle. These data constitute the beginning of a reference data set of the normal mammary gland, which can be consulted for comparison with data developed from malignant specimens, or to mine the effects of the hormonal flux that occurs during the menstrual cycle. PMID:24636070

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

    PubMed

    Wang, Rui-Hua

    2015-05-01

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

  16. [The specific erythrocyte adherence method in the study of ABH antigens on normal and neoplastic bladder epithelium].

    PubMed

    Ongaro, G; Issi, M; Gallo, T; Garbeglio, A; Ranieri, A; Dalla Palma, P

    1983-06-01

    The isoantigens A, B, and H, identical with those present in erythrocytes, are also present in epithelial cells of some normal tissues, included the transitional epithelium of the urinary bladder. The cell surface ABH antigens can be detected with the specific erythrocyte adherence method (SEA), but could not be detected when carcinoma developed in this tissue: with rare exceptions, the loss of demonstrable antigens paralleled morphological anaplasia. We studied retrospectively by SEA test 51 specimens of urinary bladder, including 36 primary transitional cell carcinomas at the time of initial biopsy, and 15 controls. The SEA reaction was strongly positive in normal bladder epithelium, in vascular endothelium and in erythrocytes already present in sections, while was negative in connective tissue. 21 were classified as grade 0 (papilloma): in 19 of them the ABH antigens were fully or partially preserved, and the follow up from 5 to 15 years demonstrated no recurrences; the other 2 patients with negative SEA recurred locally. The only one graded as I, with strongly positive SEA, had not recurred in at least 6 years, 5 were classified as grade II; in 2 of graded as III, the SEA reaction was weakly positive in 3, while in remaining 6 the antigens were absent. The usefulness of the detection of ABH antigens as a prognostic tool in low grade and stage bladder carcinomas is confirmed by our data establishing the correlation of antigens deletion with subsequent clinical behavior. An alteration of blood group substance synthesis occurs in malignant epithelium, but it is not known whether it causes or results from malignant changes. The SEA method resulted highly sensitive and specific; however, the test is cumbersome and time-consuming, requires special expertise and shows some limitations, particularly the frequency of the occurrence of false-negative or weakly positive results in blood group O patients. PMID:6676774

  17. A normal and biotransforming model of the human bronchial epithelium for the toxicity testing of aerosols and solubilised substances.

    PubMed

    Prytherch, Zo C; BruB, Kelly A

    2014-12-01

    In this article, we provide an overview of the experimental workflow by the Lung and Particle Research Group at Cardiff University, that led to the development of the two in vitro lung models - the normal human bronchial epithelium (NHBE) model and the lung-liver model, Metabo-Lung. This work was jointly awarded the 2013 Lush Science Prize. The NHBE model is a three-dimensional, in vitro, human tissue-based model of the normal human bronchial epithelium, and Metabo-Lung involves the co-culture of the NHBE model with primary human hepatocytes, thus permitting the biotransformation of inhaled toxicants in an in vivo-like manner. Both models can be used as alternative test systems that could replace the use of animals in research and development for safety and toxicity testing in a variety of industries (e.g. the pharmaceutical, environmental, cosmetics, and food industries). Metabo-Lung itself is a unique tool for the in vitro detection of toxins produced by reactive metabolites. This 21st century animal replacement model could yield representative in vitro predictions for in vivo toxicity. This advancement in in vitro toxicology relies on filter-well technology that will enable a wide-spectrum of researchers to create viable and economic alternatives for respiratory safety assessment and disease-focused research. PMID:25635646

  18. Phototoxic Action Spectrum on a Retinal Pigment Epithelium Model of Age-Related Macular Degeneration Exposed to Sunlight Normalized Conditions

    PubMed Central

    Arnault, Emilie; Barrau, Coralie; Nanteau, Cline; Gondouin, Pauline; Bigot, Karine; Vinot, Franoise; Gutman, Emmanuel; Fontaine, Valrie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, Jos-Alain; Picaud, Serge

    2013-01-01

    Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye. PMID:24058402

  19. 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

  20. Fatty acid synthase expression and esophageal cancer.

    PubMed

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

    2012-10-01

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

  1. 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.

  2. Reversal of lower esophageal sphincter hypotension and esophageal aperistalsis after treatment for hypothyroidism.

    PubMed

    Eastwood, G L; Braverman, L E; White, E M; Vander Salm, T J

    1982-08-01

    A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with 131I and documented a fall in LES pressure. We propose that abnormal smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism. PMID:7119407

  3. Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.

    PubMed

    Xu, Z; Dong, Y; Peng, F; Yu, Z; Zuo, Y; Dai, Z; Chen, Y; Wang, J; Hu, X; Zhou, Q; Ma, H; Bao, Y; Gao, G; Chen, M

    2015-03-01

    This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation. PMID:25591809

  4. The initial establishment and epithelial morphogenesis of the esophagus: a new model of tracheal-esophageal separation and transition of simple columnar into stratified squamous epithelium in the developing esophagus.

    PubMed

    Que, Jianwen

    2015-01-01

    The esophagus and trachea are tubular organs that initially share a single common lumen in the anterior foregut. Several models have been proposed to explain how this single-lumen developmental intermediate generates two tubular organs. However, new evidence suggests that these models are not comprehensive. I will first briefly review these models and then propose a novel 'splitting and extension' model based on our in vitro modeling of the foregut separation process. Signaling molecules (e.g., SHHs, WNTs, BMPs) and transcription factors (e.g., NKX2.1 and SOX2) are critical for the separation of the foregut. Intriguingly, some of these molecules continue to play essential roles during the transition of simple columnar into stratified squamous epithelium in the developing esophagus, and they are also closely involved in epithelial maintenance in the adults. Alterations in the levels of these molecules have been associated with the initiation and progression of several esophageal diseases and cancer in adults. PMID:25727889

  5. Targeting chemokine pathways in esophageal adenocarcinoma

    PubMed Central

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

    2014-01-01

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

  6. Stimulation of the proliferation of human normal esophageal epithelial cells by fumonisin B1 and its mechanism

    PubMed Central

    WANG, SHAO-KANG; WANG, TING-TING; HUANG, GUI-LING; SHI, RUO-FU; YANG, LI-GANG; SUN, GUI-JU

    2014-01-01

    Previous epidemiological studies have demonstrated a correlation between fumonisin B1 (FB1) and human esophageal cancer in China, Iran and South Africa. The purpose of this study was to investigate the effects of FB1 on the proliferation, cell-cycle and apoptosis of normal human esophageal epithelial cells (HEECs) and to explore the molecular mechanisms of these effects. The proliferation of HEECs treated with FB1 was assessed using a colorimetric assay, while analyses of the cell cycle and apoptosis were performed using flow cytometry and the measurement of the protein expressions of genes associated with the cell cycle was conducted using western blotting. The results showed that FB1 stimulated the proliferation of HEECs, decreased the percentage of cells in the G0/G1 phase and reduced apoptosis. The western blotting results showed that FB1 significantly increased the protein expression of cyclin D1 and significantly decreased the protein expression of cyclin E, p21 and p27. The results indicated that FB1 stimulated the proliferation of HEECs by affecting the cell cycle and apoptosis. This mechanism was associated with changes in cyclin D1, cyclin E, p21 and p27 expression. PMID:24348764

  7. Role of Lynx1 and related Ly6 proteins as modulators of cholinergic signaling in normal and neoplastic bronchial epithelium.

    PubMed

    Fu, Xiao Wen; Song, Ping Fang; Spindel, Eliot R

    2015-11-01

    The ly-6 proteins are a large family of proteins that resemble the snake three finger alpha toxins such as ?-bungarotoxin and are defined by their multiple cysteine residues. Multiple members of the ly-6 protein family can modulate nicotinic signaling including lynx1, lynx2, slurp-1, slurp-2 and prostate stem cell antigen (PSCA). Consistent with the expression of multiple nicotinic receptors in bronchial epithelium, multiple members of the nicotinic-modulatory ly-6 proteins are expressed in lung including lynx1 and lynx2. We studied the role of lynx1 as an exemplar of the role of ly-6 proteins in lung. Our data demonstrates that lynx1 acts as a negative modulator of nicotinic signaling in normal and neoplastic lung. In normal lung lynx1 serves to limit the ability of chronic nicotine exposure to increase levels of nicotinic receptors and also serves to limit the ability of nicotine to upregulate levels of GABAA receptors in lung. In turn this allows lynx1 to limit the ability of nicotine to upregulate levels of mucin which is mediated by GABAergic signaling. This suggests that lynx1-mimetics may have potential for treatment of asthma and COPD. In that most lung cancer cells also express nicotinic receptor and lynx1 we examined the role of lynx-1 in lung cancer. Lynx1 levels are decreased in lung cancers compared to adjacent normal lung. Knockdown of lynx1 by siRNAs increased growth of lung cancer cells while expression of lynx1 in lung cancer cell decreased cell proliferation. This suggests that lynx1 is an endogenous regulator of lung cancer growth. Given that multiple small molecule negative and positive allosteric modulators of nicotinic receptors have already been developed, this suggests that lynx1 is a highly druggable target both for development of drugs that may limit lung cancer growth as well as for drugs that may be effective for asthma or COPD treatment. PMID:26025503

  8. Hormone-sensing cells require Wip1 for paracrine stimulation in normal and premalignant mammary epithelium

    PubMed Central

    2013-01-01

    Introduction The molecular circuitry of different cell types dictates their normal function as well as their response to oncogene activation. For instance, mice lacking the Wip1 phosphatase (also known as PPM1D; protein phosphatase magnesium-dependent 1D) have a delay in HER2/neu (human epidermal growth factor 2), but not Wnt1-induced mammary tumor formation. This suggests a cell type-specific reliance on Wip1 for tumorigenesis, because alveolar progenitor cells are the likely target for transformation in the MMTV(mouse mammary tumor virus)-neu but not MMTV-wnt1 breast cancer model. Methods In this study, we used the Wip1-knockout mouse to identify the cell types that are dependent on Wip1 expression and therefore may be involved in the early stages of HER2/neu-induced tumorigenesis. Results We found that alveolar development during pregnancy was reduced in Wip1-knockout mice; however, this was not attributable to changes in alveolar cells themselves. Unexpectedly, Wip1 allows steroid hormone-receptor-positive cells but not alveolar progenitors to activate STAT5 (signal transducer and activator of transcription 5) in the virgin state. In the absence of Wip1, hormone-receptor-positive cells have significantly reduced transcription of RANKL (receptor activator of nuclear factor kappa-B ligand) and IGF2 (insulin-like growth factor 2), paracrine stimulators of alveolar development. In the MMTV-neu model, HER2/neu activates STAT5 in alveolar progenitor cells independent of Wip1, but HER2/neu does not override the defect in STAT5 activation in Wip1-deficient hormone-sensing cells, and paracrine stimulation remains attenuated. Moreover, ERK (extracellular signal-regulated kinase) activation by HER2/neu in hormone-sensing cells is also Wip1 dependent. Conclusions We identified Wip1 as a potentiator of prolactin and HER2/neu signaling strictly in the molecular context of hormone-sensing cells. Furthermore, our findings highlight that hormone-sensing cells convert not only estrogen and progesterone but also prolactin signals into paracrine instructions for mammary gland development. The instructive role of hormone-sensing cells in premalignant development suggests targeting Wip1 or prolactin signaling as an orthogonal strategy for inhibiting breast cancer development or relapse. PMID:23369183

  9. 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, TGF?1, 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

  10. A histometric/scanning electron microscope study of normal and loaded oral epithelium of the vervet monkey.

    PubMed Central

    Grossman, E S

    1987-01-01

    To investigate the functional significance of the epithelial cell surface features found in oral mucosa, a histometric analysis of the pits, microvilli and microplications was carried out in normal and mechanically loaded attached gingiva and alveolar mucosa of the vervet monkey throughout the full thickness of the epithelium. An electronic image analysing system and point counting methods were used to obtain the necessary data from micrographs of tissue specimens viewed in the scanning electron microscope. The results indicate that the cell area increases and the density of microvilli and microplications decreases from the deepest to the superficial cell layers. There was no statistically significant difference between the diameter of the pits and microvilli in the attached gingiva. Similarly there was no statistically significant difference between the widths of the grooves on the oral cell surface and the microplications on the under-surfaces of the alveolar mucosa cells. This indicates that the cell surfaces are complementary within each tissue type. Furthermore mechanical loading caused a significant decrease in the density of microvilli and microplications in the two tissues, confirming that these structures serve as reserve areas for cell stretching. Images p85-a p85-b Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:3446668

  11. Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium

    NASA Technical Reports Server (NTRS)

    Shim, Veronica; Gauthier, Mona L.; Sudilovsky, Daniel; Mantei, Kristin; Chew, Karen L.; Moore, Dan H.; Cha, Imok; Tlsty, Thea D.; Esserman, Laura J.

    2003-01-01

    Cyclooxygenase-2 (COX-2) is emerging as an important cancer biomarker and is now an experimental target for solid tumor treatment.However, no study has exclusively focused on COX-2 expression in early lesions such as ductal carcinoma in situ (DCIS). We examined COX-2 expression by immunohistochemistry in 46 cases of women undergoing surgical resection for DCIS. We found that COX-2 expression was detected in 85% of all DCIS specimens, with increased COX-2 staining correlating with higher nuclear grade. Strikingly, COX-2 staining intensity in the normal adjacent epithelium was stronger than in the DCIS lesion itself. Our observations demonstrate that COX-2 is up-regulated in the normal adjacent epithelium and supports the hypothesis that the surrounding epithelial tissue is part of the disease process in DCIS.

  12. p120-Catenin Down-Regulation and Epidermal Growth Factor Receptor Overexpression Results in a Transformed Epithelium That Mimics Esophageal Squamous Cell Carcinoma

    PubMed Central

    Lehman, Heather L.; Yang, Xuebin; Welsh, Patricia A.; Stairs, Douglas B.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a poor prognosis due to its highly invasive and metastatic potential. The molecular pathogenesis underlying the invasive mechanism of ESCC is not well known because of the lack of existing models to study this disease. p120-Catenin (p120ctn) and the epidermal growth factor receptor (EGFR) have each been implicated in several cancers, including ESCC. p120ctn is down-regulated in 60% of ESCC tumors, whereas EGFR is the most commonly overexpressed oncogene in ESCC. For these reasons, we investigated the cooperation between p120ctn and EGFR and its effect on ESCC invasion. We show that p120ctn down-regulation is commonly associated with EGFR overexpression. By using a three-dimensional culture system, we demonstrate that the inverse relationship between p120ctn and EGFR has biological implications. Specifically, p120ctn down-regulation coupled with EGFR overexpression in human esophageal keratinocytes (EPC1-PE) was required to promote invasion. Morphological comparison of EPC1-PE cells grown in three-dimensional culture and human ESCC revealed identical features, including significantly increased cellularity, nuclear grade, and proliferation. Molecular characteristics were measured by keratin expression patterns, which were nearly identical between EPC1-PE cells in three-dimensional culture and ESCC samples. Altogether, our analyses have demonstrated that p120ctn down-regulation and EGFR overexpression are able to mimic human ESCC in a relevant three-dimensional culture model. PMID:25529795

  13. Esophageal development and epithelial homeostasis.

    PubMed

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

    2015-08-15

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

  14. Recombinant human endostatin enhances the radioresponse in esophageal squamous cell carcinoma by normalizing tumor vasculature and reducing hypoxia

    PubMed Central

    Zhu, Hongcheng; Yang, Xi; Ding, Yuqiong; Liu, Jia; Lu, Jing; Zhan, Liangliang; Qin, Qin; Zhang, Hao; Chen, Xiaochen; Yang, Yuehua; Yang, Yan; Liu, Zheming; Yang, Meiling; Zhou, Xifa; Cheng, Hongyan; Sun, Xinchen

    2015-01-01

    The aim of this study was to investigate the effect of recombinant human endostatin (rh-Endo) in combination with radiation therapy (RT) on esophageal squamous cell carcinoma (ESCC) and explore the potential mechanisms. ECA109-bearing nude mice were administered RT and/or rh-Endo treatment. Tumor volume, survival, hypoxia and vascular parameters were recorded during the treatment schedule and follow-up as measures of treatment response. ESCC cell lines (ECA109 and TE13) and human umbilical vein endothelial cells (HUVECs) were developed to investigate the outcomes and toxicities of rh-Endo and RT in vitro. Hypoxia inducible factor-1? (HIF-1?) and vascular endothelial growth factor (VEGF) were also evaluated. In vivo studies of ECA109-bearing xenografts showed that rh-Endo improved the radioresponse, with normalization of tumor vasculature and a reduction in hypoxia. In vitro studies showed that rh-Endo did not radiosensitize ESCC cell lines but did affect endothelial cells with a time- and dose-dependent manner. Studies of the molecular mechanism indicated that the improved radioresponse might be due to crosstalk between cancer cells and endothelial cells involving HIF and VEGF expression. Our data suggest that rh-Endo may be a potential anti-angiogenic agent in ESCC especially when combined with RT. The improved radioresponse arises from normalization of tumor vasculature and a reduction in hypoxia. PMID:26412785

  15. Barrett's esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa and treatment of superficial esophageal cancer

    NASA Astrophysics Data System (ADS)

    Overholt, Bergein F.; Panjehpour, Masoud

    1995-03-01

    Fifteen patients with Barrett's esophagus and dysplasia were treated with photodynamic therapy. Four patients also had early, superficial esophageal cancers and 5 had esophageal polyps. Light was delivered via a standard diffuser or a centering esophageal balloon. Eight patients maintained on omeprazole and followed for 6 - 54 months are the subject of this report. Photodynamic therapy ablated dysplastic or malignant mucosa in patients with superficial cancer. Healing and partial replacement of Barrett's mucosa with normal squamous epithelium occurred in all patients and complete replacement with squamous epithelium was found in two. Side effects included photosensitivity and mild-moderate chest pain and dysphagia for 5 - 7 days. In three patients with extensive circumferential mucosal ablation in the proximal esophagus, healing was associated with esophageal strictures which were treated successfully by esophageal dilation. Strictures were not found in the distal esophagus. Photodynamic therapy combined with long-term acid inhibition provides effective endoscopic therapy of Barrett's mucosal dysplasia and superficial (Tis-T1) esophageal cancer. The windowed centering balloon improves delivery of photodynamic therapy to diffusely abnormal esophageal mucosa.

  16. From reflux esophagitis to Barretts esophagus and esophageal adenocarcinoma

    PubMed Central

    Wang, Rui-Hua

    2015-01-01

    The occurrence of gastroesophageal reflux disease is common in the human population. Almost all cases of esophageal adenocarcinoma are derived from Barretts 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 Barretts 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 Barretts esophagus, which should help to develop better prevention and treatment strategies for Barretts esophagus. PMID:25954094

  17. The initial establishment and epithelial morphogenesis of the esophagus: a new model of tracheal–esophageal separation and transition of simple columnar into stratified squamous epithelium in the developing esophagus

    PubMed Central

    Que, Jianwen

    2016-01-01

    The esophagus and trachea are tubular organs that initially share a single common lumen in the anterior foregut. Several models have been proposed to explain how this single-lumen developmental intermediate generates two tubular organs. However, new evidence suggests that these models are not comprehensive. I will first briefly review these models and then propose a novel ‘splitting and extension’ model based on our in vitro modeling of the foregut separation process. Signaling molecules (e.g., SHHs, WNTs, BMPs) and transcription factors (e.g., NKX2.1 and SOX2) are critical for the separation of the foregut. Intriguingly, some of these molecules continue to play essential roles during the transition of simple columnar into stratified squamous epithelium in the developing esophagus, and they are also closely involved in epithelial maintenance in the adults. Alterations in the levels of these molecules have been associated with the initiation and progression of several esophageal diseases and cancer in adults. PMID:25727889

  18. AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells

    PubMed Central

    Fuhrmann, A; Staunton, J R; Nandakumar, V; Banyai, N; Davies, P C W; Ros, R

    2011-01-01

    The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division, and motility, and the epithelial-mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barretts Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope (FLIM) to study the mechanical properties of single adherent cells. 64 force indentation curves were taken over the nucleus of each cell in an 88 grid pattern. Analyzing the force indentation curves, indentation depth dependent Youngs moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Youngs moduli were calculated to 4.7 kPa for EPC2 (n=18 cells), 3.1 kPa for CP-A (n=10), and 2.6 kPa for CP-D (n=19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n=5), significant stiffening was found (9.9 kPa), while CP-A cells (n=5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n=16). Some force-indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these breakthrough events to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells, and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to crumble and yield rather than their ability to bend and flex. PMID:21301067

  19. An extended proximal esophageal myotomy is necessary to normalize EGJ distensibility during Heller myotomy for achalasia, but not POEM

    PubMed Central

    Teitelbaum, Ezra N.; Soper, Nathaniel J.; Pandolfino, John E.; Kahrilas, Peter J.; Boris, Lubomyr; Nicodème, Frédéric; Lin, Zhiyue; Hungness, Eric S.

    2015-01-01

    Background For laparoscopic Heller myotomy (LHM), the optimal myotomy length proximal to the esophagogastric junction (EGJ) is unknown. In this study, we used a functional lumen imaging probe (FLIP) to measure EGJ distensibility changes resulting from variable proximal myotomy lengths during LHM and peroral esophageal myotomy (POEM). Methods Distensibility index (DI) (defined as the minimum cross-sectional area at the EGJ divided by pressure) was measured with FLIP after each operative step. During LHM and POEM, each patient’s myotomy was performed in two stages: first, a myotomy ablating only the EGJ complex was created (EGJ-M), extending from 2cm proximal to the EGJ, to 3cm distal to it. Next, the myotomy was lengthened 4cm further cephalad to create an extended proximal myotomy (EP-M). Results Measurements were performed in 12 patients undergoing LHM and 19 undergoing POEM. LHM resulted in an overall increase in DI (1.6 ±1 vs. 6.3 ±3.4 mm2/mmHg, p<.001). Creation of an EGJ-M resulted in a small increase (1.6 to 2.3 mm2/mmHg, p<.01) and extension to an EP-M resulted in a larger increase (2.3 to 4.9 mm2/mmHg, p<.001). This effect was consistent, with 11 (92%) patients experiencing a larger increase after EP-M than after EGJ-M. Fundoplication resulted in a decrease in DI and deinsufflation an increase. POEM resulted in an increase in DI (1.3 ±1 vs. 9.2 ±3.9 mm2/mmHg, p<.001). Both creation of the submucosal tunnel and performing an EGJ-M increased DI, whereas lengthening of the myotomy to an EP-M had no additional effect. POEM resulted in a larger overall increase from baseline than LHM (7.9 ±3.5 vs. 4.7 ±3.3 mm2/mmHg, p<.05). Conclusions During LHM, an extended proximal myotomy was necessary to normalize distensibility, whereas during POEM, a myotomy confined to the EGJ complex was sufficient. In this cohort, POEM resulted in a larger overall increase in EGJ distensibility. PMID:24853854

  20. Esophageal Cancer

    MedlinePLUS

    ... More information Clinical Trials to Screen for Esophageal Cancer Statistics Esophageal cancer statistics based on data from large groups of patients to be used as a general guide. General Resources on Coping ... for both patients and caregivers. National ...

  1. 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 ...

  2. 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 ...

  3. Intensity-Modulated Proton Therapy Further Reduces Normal-Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    PubMed Central

    Welsh, James; Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V; Komaki, Ritsuko; Dong, Lei; Zhu, X. Ronald; Likhacheva, Anna; Liao, Zhongxing; Hofstetter, Wayne L.; Ajani, Jaffer A.; Cox, James D.

    2014-01-01

    Purpose We previously found that up to 75% of treatment failures after chemoradiation for unresectable esophageal cancer appear within the gross tumor volume (GTV) and that intensity-modulated [photon] radiation therapy (IMRT) may allow dose escalation to the tumor without increasing normal-tissue toxicity. Proton therapy may allow further dose escalation with even lower normal-tissue toxicity. Here we compared dosimetric parameters for photon IMRT with intensity-modulated proton therapy (IMPT) for unresectable, locally advanced distal esophageal cancer. Methods and Materials Four plans were created for each of 10 patients: IMPT delivered via anteroposterior/posteroanterior (AP/PA) beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams; and IMRT delivered with a concomitant boost to the GTV. Doses were 65.8 Gy to the GTV and 50.4 Gy to the planning target volume (PTV) in 28 fractions. Results Relative to IMRT, the IMPT (AP/PA) plan led to considerable reductions in mean lung dose (3.18 Gy vs 8.27 Gy, p<0.0001) and in lung V5, V10, and V20 (p?0.0006) but did not reduce cardiac dose; the IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs 8.2 Gy, p<0.001) as well as reducing heart doses (mean cardiac dose and cardiac V10, V20, and V30, p?0.02) and liver doses (mean hepatic dose 5 Gy vs 14.9 Gy, p<0.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in dose to the lung (p?0.005), heart (p?0.003), and liver (p?0.04). Conclusions Compared with IMRT, IMPT for distal esophageal cancer can lower the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to tailored to each patient based on their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigate further in a prospective trial at our institution. PMID:21470796

  4. Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    SciTech Connect

    Welsh, James; Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko; Dong, Lei; Zhu, X. Ronald; Likhacheva, Anna; Liao, Zhongxing; Hofstetter, Wayne L.; Ajani, Jaffer A.; Cox, James D.

    2011-12-01

    Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution.

  5. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    SciTech Connect

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    We previously established a rapid three-dimensional assay for discrimination of normal and malignant human breast epithelial cells using a laminin-rich reconstituted basement membrane. In this assay, normal epithelial cells differentiate into well-organized acinar structures whereas tumor cells fail to recapitulate this process and produce large, disordered colonies. The data suggest that breast acinar morphogenesis and differentiation is regulated by cell-extracellular matrix (ECM) interactions and that these interactions are altered in malignancy. Here, we investigated the role of ECM receptors (integrins) in these processes and report on the expression and function of potential laminin receptors in normal and tumorigenic breast epithelial cells. Immmunocytochemical analysis showed that normal and carcinoma cells in a three-dimensional substratum express profiles of integrins similar to normal and malignant breast tissues in situ. Normal cells express {alpha}1, {alpha}2, {alpha}3, {alpha}6, {beta}1 and {beta}4 integrin subunits, whereas breast carcinoma cells show variable losses, disordered expression, or down regulation of these subunits. Function-blocking experiments using inhibitory antiintegrin subunit antibodies showed a >5-fold inhibition of the formation of acinar structures by normal cells in the presence of either anti-{beta}1 or anti-{alpha}3 antibodies, whereas anti-{alpha}2 or -{alpha}6 had little or no effect. In experiments where collagen type I gels were used instead of basement membrane, acinar morphogenesis was blocked by anti-{beta}1 and -{alpha}2 antibodies but not by anti-{alpha}3. These data suggest a specificity of integrin utilization dependent on the ECM ligands encountered by the cell. The interruption of normal acinar morphogenesis by anti-integrin antibodies was associated with an inhibition of cell growth and induction of apoptosis. Function-blocking antibodies had no inhibitory effect on the rate of tumor cell growth, survival or capacity to form colonies. Thus under our culture conditions breast acinar formation is at least a two-step process involving {beta}1-integrin-dependent cellular growth followed by polarization of the cells into organized structures. The regulation of this pathway appears to be impaired or lost in the tumor cells, suggesting that tumor colony formation occurs by independent mechanisms and that loss of proper integrinmediated cell-ECM interaction may be critical to breast tumor formation.

  6. Lower pH values of weakly acidic refluxes as determinants of heartburn perception in gastroesophageal reflux disease patients with normal esophageal acid exposure.

    PubMed

    de Bortoli, N; Martinucci, I; Savarino, E; Franchi, R; Bertani, L; Russo, S; Ceccarelli, L; Costa, F; Bellini, M; Blandizzi, C; Savarino, V; Marchi, S

    2016-01-01

    Multichannel impedance pH monitoring has shown that weakly acidic refluxes are able to generate heartburn. However, data on the role of different pH values, ranging between 4 and 7, in the generation of them are lacking. The aim of this study was to evaluate whether different pH values of weakly acidic refluxes play a differential role in provoking reflux symptoms in endoscopy-negative patients with physiological esophageal acid exposure time and positive symptom index and symptom association probability for weakly acidic refluxes. One hundred and forty-three consecutive patients with gastroesophageal reflux disease, nonresponders to proton pump inhibitors (PPIs), were allowed a washout from PPIs before undergoing: upper endoscopy, esophageal manometry, and multichannel impedance pH monitoring. In patients with both symptom index and symptom association probability positive for weakly acidic reflux, each weakly acidic reflux was evaluated considering exact pH value, extension, physical characteristics, and correlation with heartburn. Forty-five patients with normal acid exposure time and positive symptom association probability for weakly acidic reflux were identified. The number of refluxes not heartburn related was higher than those heartburn related. In all distal and proximal liquid refluxes, as well as in distal mixed refluxes, the mean pH value of reflux events associated with heartburn was significantly lower than that not associated. This condition was not confirmed for proximal mixed refluxes. Overall, a low pH of weakly acidic reflux represents a determinant factor in provoking heartburn. This observation contributes to better understand the pathophysiology of symptoms generated by weakly acidic refluxes, paving the way toward the search for different therapeutic approaches to this peculiar condition of esophageal hypersensitivity. PMID:25212408

  7. Defective Barrier Function in Neosquamous Epithelium

    PubMed Central

    Jovov, Biljana; Shaheen, Nicholas J; Orlando, Geraldine S.; Djukic, Zorka; Orlando, Roy C.

    2013-01-01

    BACKGROUND Radiofrequency ablation (RFA) of Barretts esophagus (BE) is a common strategy for the prevention of esophageal adenocarcinoma (EAC). After RFA, the ablated esophagus heals on acid suppressive therapy, and is re-populated with a stratified squamous epithelium, referred to as neosquamous epithelium (NSE). Because the ability of the NSE to protect the underlying tissue from recurrent insult by reflux is unclear, we assessed the barrier function of NSE by comparing it to that of the native upper squamous epithelium (USE) in subjects having undergone RFA. METHODS At varying intervals following RFA, the barrier function of NSE and USE were assessed in endoscopic biopsies by light and electron microscopy, and by measurement of electrical resistance (RT) and fluorescein flux in mini-Ussing chambers. Chamber results were further compared with results from control biopsies (healthy distal esophagus). A claudin expression profile in the tight junctions (TJ) of NSE and USE was determined using qRT-PCR. Differential expression of claudin 4 between NSE and USE was assayed by immunoblots. RESULTS USE was histologically normal while NSE showed dilated intercellular spaces and marked eosinophilia. NSE was also more permeable than USE and healthy controls, having lower mean RT and higher fluorescein fluxes. Abnormally low RT values for NSE were unrelated to the time period following RFA (or number of prior RFA sessions), being abnormal even 26 months after RFA. Abnormal permeability in NSE was associated with significantly lower values for claudin-4 and claudin-10 than in USE. CONCLUSIONS NSE commonly exhibits defective barrier function. Since this defect will make it vulnerable to injury, inflammation and destruction by acidic and weakly acidic refluxates, it may in part explain incidences of recurrence of BE following ablation. PMID:23318477

  8. Esophageal disease in scleroderma.

    PubMed

    Ebert, Ellen C

    2006-10-01

    Progressive systemic sclerosis (PSS) causes smooth muscle atrophy and fibrosis of the distal two-thirds of the esophagus. Motility studies show reduced-amplitude or absent peristaltic contractions in this region and normal or decreased lower esophageal sphincter pressure. Patients complain of dysphagia, heartburn, and regurgitation due to reflux and dysmotility. Complications include strictures found in 17% to 29% of patients and Barrett esophagus is 0% to 37%. Candida esophagitis is a complication of PSS not seen with non-PSS reflux. Esophageal disease correlates with pulmonary involvement but not with disease in the stomach or intestines. Whether reflux contributes to the pulmonary disease is an open question. Although manometry is the gold standard for diagnosis, cine-esophagram and scintography are only slightly less sensitive and should be considered for following the patients. Symptoms correlate poorly with evidence of esophagitis or abnormal 24-hour pH recordings. As a result, it is unclear which patients should receive acid-reducing or prokinetic medications and which medication to use. Aspiration precautions are important in those with severe esophageal dysmotility. This review of the literature highlights many areas of uncertainty in the diagnosis and treatment of esophageal disease in PSS that can be addressed in clinical studies. PMID:17016130

  9. Variable deletion of exon 9 coding sequences in cystic fibrosis transmembrane conductance regulator gene mRNA transcripts in normal bronchial epithelium.

    PubMed Central

    Chu, C S; Trapnell, B C; Murtagh, J J; Moss, J; Dalemans, W; Jallat, S; Mercenier, A; Pavirani, A; Lecocq, J P; Cutting, G R

    1991-01-01

    The predicted protein domains coded by exons 9-12 and 19-23 of the 27 exon cystic fibrosis transmembrane conductance regulator (CFTR) gene contain two putative nucleotide-binding fold regions. Analysis of CFTR mRNA transcripts in freshly isolated bronchial epithelium from 12 normal adult individuals demonstrated that all had some CFTR mRNA transcripts with exon 9 completely deleted (exon 9- mRNA transcripts). In most (9 of 12), the exon 9- transcripts represented less than or equal to 25% of the total CFTR transcripts. However, in three individuals, the exon 9- transcripts were more abundant, comprising 39, 62 and 66% of all CFTR transcripts. Re-evaluation of the same individuals 2-4 months later showed the same proportions of exon 9- transcripts. Of the 24 CFTR alleles in the 12 individuals, the sequences of the exon-intron junctions relevant to exon 9 deletion (exon 8-intron 8, intron 8-exon 9, exon 9-intron 9, and intron 9-exon 10) were identical except for the intron 8-exon 9 region sequences. Several individuals had varying lengths of a TG repeat in the region between splice branch and splice acceptor consensus sites. Interestingly, one allele in each of the two individuals with 62 and 66% exon 9- transcripts had a TT deletion in the splice acceptor site for exon 9. These observations suggest either the unlikely possibility that sequences in exon 9 are not critical for the functioning of the CFTR or that only a minority of the CFTR mRNA transcripts need to contain exon 9 sequences to produce sufficient amounts of a normal CFTR to maintain a normal clinical phenotype. Images PMID:1709095

  10. [Reflux esophagitis: respective roles of esophageal and gastric pathogenic factors].

    PubMed

    Bruley des Varannes, S; Touchais, J Y; Weber, J; Desechalliers, J P; Sauger, F; Denis, P; Galmiche, J P

    1986-10-01

    Multiple factors contribute to the production of esophagitis in gastroesophageal reflux (GER), but the respective roles of esophageal (i. e. lower esophageal sphincter (LES) tone, peristalsis) and gastric factors (i. e. acid secretion and gastric emptying) are not well known. The aim of this work was to study the frequency and the severity of esophageal and gastric abnormalities observed in the same patients and to correlate these findings with the degree of esophagitis. Thirty-three consecutive patients with GER proven by esophageal pH recording (3-hr postprandial pH-test) were classified according to the presence (group A, n = 18) or absence (group B, n = 15) of severe esophagitis (i. e. erosions, ulcerations, or stenosis) at endoscopy. LES basal tone and esophageal peristalsis were studied by manometry. Gastric acid secretion and emptying of liquids were measured by intragastric titration coupled with the dye dilution technique. Results obtained in GER patients were compared with those found in twenty-three normal subjects. Hypotonia of LES (i. e. LES tone less than 7 cm H2O) was more frequent in group A (72 p. 100) than in group B patients (30 p. 100, p less than 0.05). Magnitude of esophageal peristaltic waves was lower in group A than in group B (p less than 0.10). When compared to values found in normal subjects, gastric emptying and acid secretion were not significantly different both in presence and in absence of esophagitis. There was no linear correlation between esophageal pH parameters and acid secretion values or gastric emptying rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3792741

  11. A Zebrafish Model for Studies on Esophageal Epithelial Biology.

    PubMed

    Chen, Hao; Beasley, Andrea; Hu, Yuhui; Chen, Xiaoxin

    2015-01-01

    Mammalian esophagus exhibits a remarkable change in epithelial structure during the transition from embryo to adult. However, the molecular mechanisms of esophageal epithelial development are not well understood. Zebrafish (Danio rerio), a common model organism for vertebrate development and gene function, has not previously been characterized as a model system for esophageal epithelial development. In this study, we characterized a piece of non-keratinized stratified squamous epithelium similar to human esophageal epithelium in the upper digestive tract of developing zebrafish. Under the microscope, this piece was detectable at 5dpf and became stratified at 7dpf. Expression of esophageal epithelial marker genes (Krt5, P63, Sox2 and Pax9) was detected by immunohistochemistry and in situ hybridization. Knockdown of P63, a gene known to be critical for esophageal epithelium, disrupted the development of this epithelium. With this model system, we found that Pax9 knockdown resulted in loss or disorganization of the squamous epithelium, as well as down-regulation of the differentiation markers Krt4 and Krt5. In summary, we characterized a region of stratified squamous epithelium in the zebrafish upper digestive tract which can be used for functional studies of candidate genes involved in esophageal epithelial biology. PMID:26630178

  12. A Zebrafish Model for Studies on Esophageal Epithelial Biology

    PubMed Central

    Chen, Hao; Beasley, Andrea; Hu, Yuhui; Chen, Xiaoxin

    2015-01-01

    Mammalian esophagus exhibits a remarkable change in epithelial structure during the transition from embryo to adult. However, the molecular mechanisms of esophageal epithelial development are not well understood. Zebrafish (Danio rerio), a common model organism for vertebrate development and gene function, has not previously been characterized as a model system for esophageal epithelial development. In this study, we characterized a piece of non-keratinized stratified squamous epithelium similar to human esophageal epithelium in the upper digestive tract of developing zebrafish. Under the microscope, this piece was detectable at 5dpf and became stratified at 7dpf. Expression of esophageal epithelial marker genes (Krt5, P63, Sox2 and Pax9) was detected by immunohistochemistry and in situ hybridization. Knockdown of P63, a gene known to be critical for esophageal epithelium, disrupted the development of this epithelium. With this model system, we found that Pax9 knockdown resulted in loss or disorganization of the squamous epithelium, as well as down-regulation of the differentiation markers Krt4 and Krt5. In summary, we characterized a region of stratified squamous epithelium in the zebrafish upper digestive tract which can be used for functional studies of candidate genes involved in esophageal epithelial biology. PMID:26630178

  13. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.

    PubMed

    Thomas, Sushma S; Makar, Karen W; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y; Lampe, Paul D; Yan, Min; Markowitz, Sanford D; Bigler, Jeannette; Lampe, Johanna W; Potter, John D

    2015-12-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) - accession number GSE71571 - was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]). PMID:26697360

  14. Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial

    PubMed Central

    Thomas, Sushma S.; Makar, Karen W.; Li, Lin; Zheng, Yingye; Yang, Peiying; Levy, Lisa; Rudolph, Rebecca Y.; Lampe, Paul D.; Yan, Min; Markowitz, Sanford D.; Bigler, Jeannette; Lampe, Johanna W.; Potter, John D.

    2015-01-01

    Regular aspirin use reduces colon adenoma and carcinoma incidence. UDP-glucuronosyltransferases (UGT) are involved in aspirin metabolism and clearance, and variant alleles in UGT1A6 have been shown to alter salicylic acid metabolism and risk of colon neoplasia. In a randomized, cross-over, placebo-controlled trial of 44 healthy men and women, homozygous for UGT1A6*1 or UGT1A6*2, we explored differences between global epithelial and stromal expression, using Affymetrix U133 + 2.0 microarrays and tested effects of 60-day aspirin supplementation (325 mg/d) on epithelial and stromal gene expression and colon prostaglandin E2 (PGE2) levels. We conducted a comprehensive study of differential gene expression between normal human colonic epithelium and stroma from healthy individuals. Although no statistically significant differences in gene expression were observed in response to aspirin or UGT1A6 genotype, we have identified the genes uniquely and reproducibly expressed in each tissue type and have analyzed the biologic processes they represent. Here we describe in detail how the data, deposited in the Gene Expression Omnibus (GEO) – accession number GSE71571 – was generated including the basic analysis as contained in the manuscript published in BMC Medical Genetics with the PMID 25927723 (Thomas et al., 2015 [9]). PMID:26697360

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

    PubMed

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

    2014-08-01

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

  16. Cytokeratins in normal and malignant transitional epithelium. Maintenance of expression of urothelial differentiation features in transitional cell carcinomas and bladder carcinoma cell culture lines.

    PubMed Central

    Moll, R.; Achtsttter, T.; Becht, E.; Balcarova-Stnder, J.; Ittensohn, M.; Franke, W. W.

    1988-01-01

    The pattern of cytokeratins expressed in normal urothelium has been compared with that of various forms of transitional cell carcinomas (TCCs; 21 cases) and cultured bladder carcinoma cell lines, using immunolocalization and gel electrophoretic techniques. In normal urothelium, all simple-epithelium-type cytokeratins (polypeptides 7, 8, 18, 19) were detected in all cell layers, whereas antibodies to cytokeratins typical for stratified epithelia reacted with certain basal cells only or, in the case of cytokeratin 13, with cells of the basal and intermediate layers. This pattern was essentially maintained in low-grade (G1, G1/2) TCCs but was remarkably modified in G2 TCCs. In G3 TCCs simple-epithelial cytokeratins were predominant whereas the amounts of component 13 were greatly reduced. Squamous metaplasia was accompanied generally by increased or new expression of some stratified-epithelial cytokeratins. The cytokeratin patterns of cell culture lines RT-112 and RT-4 resembled those of G1 and G2 TCCs, whereas cell line T-24 was comparable to G3 carcinomas. The cell line EJ showed a markedly different pattern. The results indicate that, in the cell layers of the urothelium, the synthesis of stratification-related cytokeratins such as component 13 is inversely oriented compared with that in other stratified epithelia where these proteins are suprabasally expressed, that TCCs retain certain intrinsic cytoskeletal features of urothelium, and that different TCCs can be distinguished by their cytokeratin patterns. The potential value of these observations in histopathologic and cytologic diagnoses is discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:2456018

  17. Fascin and CK4 as Biomarkers for Esophageal Squamous Cell Carcinoma

    PubMed Central

    TAKIKITA, MIKIKO; HU, NAN; SHOU, JIAN-ZHONG; GIFFEN, CAROL; WANG, QUAN-HONG; WANG, CHAOYU; HEWITT, STEPHEN; TAYLOR, PHILIP R

    2011-01-01

    Background Several studies have suggested that fascin, cytokeratin 14 and cytokeratin 4 may have significant roles as biomarkers for the progression and survival of esophageal squamous cell carcinoma (ESCC). Methods This study performed immunohistochemistry in tissue microarrays, profiling premalignant lesions and invasive tumors. Results Fascin increased across the following states as follows: normal epithelium (26%) to dysplasia (46%) to ESCC (68%), while CK4 was undetectable in ESCC (0%) compared to normal epithelium (45%) or dysplasia (41%). CK14 was elevated and invariant in expression. In regression analyses, compared to normal epithelium, higher fascin expression was associated with a 36% increased risk of dysplasia (odds ratio=1.36) and a 56% increased risk of invasive ESCC (odds ratio=1.56). Conclusions Expression of fascin is up-regulated in the transformation from normal epithelium, through dysplasia, into invasive carcinoma. Expression of CK4, CK14 and fascin did not correlate with patient survival. Fascin has a potential role as an early detection biomarker and CK4 as a tumor marker in ESCC. PMID:21498718

  18. The pathophysiology of eosinophilic esophagitis.

    PubMed

    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-? 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

  19. Esophageal Cancer

    MedlinePLUS

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

  20. Esophageal culture

    MedlinePLUS

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

  1. Esophageal perforation

    MedlinePLUS

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

  2. Esophagitis dissecans superficialis associated with pemphigus vulgaris.

    PubMed

    Kaplan, R P; Touloukian, J; Ahmed, A R; Newcomer, V D

    1981-06-01

    A number of dermatologic conditions may have associated esophageal manifestations. Teleologically, this may be because both the skin and the esophagus are lined by stratified squamous epithelium. Bullous dermatoses that may produce blisters, erosions, and/or stricture of the esophagus include cicatricial pemphigoid, Hailey-Hailey disease, Darier's disease, various forms of epidermolysis bullosa, bullous pemphigoid, and pemphigus vulgaris. Very rarely, bullous diseases may affect the esophagus in such a manner that there is a sloughing of the entire mucous membrane. The production of such an esophageal cast has been termed esophagitis dissecans superficialis. This is the second case recorded in the medical literature of pemphigus vulgaris associated with esophagitis dissecans superficialis. Additionally, this is the first case of pemphigus vulgaris in which the esophagus is demonstrated to be positive by direct immunofluorescence. PMID:7016940

  3. Long noncoding RNA CCAT2 correlates with smoking in esophageal squamous cell carcinoma.

    PubMed

    Wang, Jie; Qiu, Mantang; Xu, Youtao; Li, Ming; Dong, Gaochao; Mao, Qixing; Yin, Rong; Xu, Lin

    2015-07-01

    Esophageal cancer is one of the leading causes of cancer-related mortality, and most esophageal squamous cell carcinoma (ESCC) cases are located in Asian area. Recent studies about long noncoding RNAs (lncRNA) have offered a new perspective for cancer research and provided new approaches to understand the complex regulation network in cancer. Our group has reported that the novel lncRNA colon cancer-associated transcript 2 (CCAT2) has important biological function and could be a potential biomarkers in lung cancer. Here, we performed in silico analysis and characterized the expression profile of CCAT2 in a cohort of esophageal squamous cell carcinoma (ESCC) patients and cell lines. In silico analysis showed that no CpG island is found in the chromosome region of CCAT2, indicating that the expression of CCAT2 is possibly not regulated by DNA methylation. Compared with paired adjacent normal esophageal tissues, CCAT2 was significantly overexpressed in ESCC tissues with an average fold of 7.18. In ESCC cell lines, CCAT2 was mostly upregulated in KYSE410 cell (24.7-fold upregulation) when normalized to normal esophageal epithelium cell line (HEEC) and most CCAT2 transcripts were located in nucleus (> 95 %). Statistical analysis showed that CCAT2 expression level was significantly associated with smoking status (P = 0.036). Receiver operative curve and the area under curve were calculated to assess the diagnostic potential of CCAT2. Measured by area under curve (AUC), CCAT2 showed higher diagnostic performance than conventional serum biomarkers, like AFP, CA153, and NSE. In this study, we firstly characterized the expression profile of CCAT2 in ESCC and evaluated its potential diagnostic value as a biomarker. PMID:25677908

  4. Nitric oxide synthase distribution in esophageal mucosa and hemodynamic changes in rats with cirrhosis

    PubMed Central

    Huang, Ying-Qiu; Xiao, Shu-Dong; Zhang, De-Zhong; Mo, Jian-Zhong

    1999-01-01

    AIM: To observe the nitric oxide synthase (NOS) distribution in the esophageal mucosa and hemodynamic changes in cirrhotic rats. METHODS: NOS distribution in the lower esophagus of rats with carbon tetrachloride-induced cirrhosis was assessed by using NADPH-diaphorase (NADPH-d) histochemical method. Concentration of NO in serum were measured by fluorometric assay. Mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI), splanchnic vascular resistance (SVR), and splanchnic blood flow (SBF) were also determined using 57Co-labled microsphere technique. RESULTS: Intensity of NOS staining in the esophageal epithelium of cirrhotic rats was significantly stronger than that in controls. There was a NOS-positive staining area in the endothelia of esophageal submucosal vessels of cirrhotic rats, but the NOS staining was negative in normal rats. NO concentration of serum in cirrhotic rats were significantly higher in comparison with that of controls. Cirrhotic rats had significantly lower MAP, SVR and higher SBF than those of the controls. CONCLUSION: Splanchnic hyperdynamic circulatory state was observed in rats with cirrhosis. The endogenous NO may play an important role in development of esophageal varices and in changes of hemodynamics in cirrhosis. PMID:11819432

  5. [Eosinophilic esophagitis].

    PubMed

    Kusunose, Hiroaki; Ohara, Shuichi

    2015-07-01

    Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. Because of elevated total IgE levels and high rates of concurrent allergic diseases compared with the general population, EoE appears to be an antigen-driven immunologic process that caused by allergens like food or aeroallergens. EoE is a disease that features dense intraepithelial infiltration by eosinophils which cause excessive mucosal immunologic reactions which cause several symptoms that mostly involve dysphagia. For establishment of the diagnosis, infiltration of eosinophils (? 20 eosinophils/HPF) should be identified in an esophageal mucosal biopsy specimen. In treatment of patients have a possibility of EoE, proton-pump inhibitors(PPIs) must be tried as first choice. Other proved therapeutic options include topical or systemic corticosteroids, chronic dietary elimination, and esophageal dilation, but local administration of glucocorticoids has recently been reported as useful therapy for EoE. PMID:26165084

  6. [Histopathological diagnosis in reflux esophagitis].

    PubMed

    Fujita, M; Kusaka, T; Hirabayashi, K; Fujimori, T

    2000-09-01

    We reviewed the histopathological features for the diagnosis of reflux esophagitis and gastroesophageal reflux disease(GERD) including carcinogenesis of the esophagus. Histologically, the presence of capillary dilatation, elongation of papillary, hyperplasia of basal layer, inflammatory cells-infiltration, balloon cells in the epithelium, and ulceration were evaluated in GERD cases. Although, histopathological changes were not clear in endoscopic-negative GERD cases, immunohistochemical examination with cell cycle protein(PCNA, p21, and p27) revealed the same abnormalities with GERD cases. In Japan, the majority cases of GERD are evaluated in grade according to Los Angeles system, therefore the prevalence of Barrett's esophagus and cancer is very low. We hypothesize that esophageal squamous cell carcinoma arising from GERD different from Barrett's cancer sequence, and clinicopathological long-term follow up will be required to assess the carcinogenesis including gene analysis. PMID:11004808

  7. Whole Genome Expression Array Profiling Highlights Differences in Mucosal Defense Genes in Barrett's Esophagus and Esophageal Adenocarcinoma

    PubMed Central

    Nancarrow, Derek J.; Clouston, Andrew D.; Smithers, B. Mark; Gotley, David C.; Drew, Paul A.; Watson, David I.; Tyagi, Sonika; Hayward, Nicholas K.; Whiteman, David C.

    2011-01-01

    Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC. PMID:21829465

  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. An experimental model of prolonged esophagitis with sphincter failure in the rat and the therapeutic potential of gastric pentadecapeptide BPC 157.

    PubMed

    Petrovic, Igor; Dobric, Ivan; Drvis, Petar; Shejbal, Drazen; Brcic, Luka; Blagaic, Alenka Boban; Batelja, Lovorka; Kokic, Neven; Tonkic, Ante; Mise, Stjepan; Baotic, Tomislav; Staresinic, Mario; Radic, Bozo; Jakir, Ana; Vuksic, Tihomir; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

    2006-11-01

    We report a simple novel rat model that combines prolonged esophagitis and parallel sphincters failure. The anti-ulcer gastric pentadecapeptide BPC 157, which was found to be stable in gastric juice, and is being evaluated in inflammatory bowel disease trials, is an anti-esophagitis therapy that recovers failed sphincters. Twelve or twenty months after the initial challenge (tubes sutured into sphincters for one week and then spontaneously removed by peristalsis), rats exhibit prolonged esophagitis (confluent hemorrhagic and yellowish lesions, thinner epithelium and superficial corneal layer, with stratification derangement); constantly lowered pressure of both sphincters (assessed by using a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through esophageal or duodenal incision); and both lower esophageal and pyloric sphincter failure. Throughout the esophagitis experiment, BPC 157 was given at either 10 micro g/kg, i.p., once a day (last application 24 h before assessment) or alternatively, it was given continuously in drinking water at 0.16 micro g/ml (12 ml/rat). This treatment recovers i) esophagitis (macroscopically and microscopically, at either region or investigated time period) and ii) pressure in both sphincters (cmH2O). In addition, BPC 157 (10 micro g/kg) or saline (1 ml/rat, 5 ml/kg) was specifically given directly into the stomach; pressure assessment was performed at 5 min thereafter. The effect of BPC 157 is specific because in normal rats, it increases lower esophageal sphincter-pressure, but decreases pyloric sphincter-pressure. Ranitidine, given as the standard drug using the same protocol (50 mg/kg, i.p., once daily; 0.83 mg/ml in drinking water; or 50 mg/kg directly into the stomach) had no effect. PMID:17116974

  10. Precancerous esophageal epithelia are associated with significantly increased scattering coefficients

    PubMed Central

    Su, Jing-Wei; Lin, Yang-Hsien; Chiang, Chun-Ping; Lee, Jang-Ming; Hsieh, Chao-Mao; Hsieh, Min-Shu; Yang, Pei-Wen; Wang, Chen-Ping; Tseng, Ping-Huei; Lee, Yi-Chia; Sung, Kung-Bin

    2015-01-01

    The progression of epithelial precancers into cancer is accompanied by changes of tissue and cellular structures in the epithelium. Correlations between the structural changes and scattering coefficients of esophageal epithelia were investigated using quantitative phase images and the scattering-phase theorem. An ex vivo study of 14 patients demonstrated that the average scattering coefficient of precancerous epithelia was 37.8% higher than that of normal epithelia from the same patient. The scattering coefficients were highly correlated with morphological features including the cell density and the nuclear-to-cytoplasmic ratio. A high interpatient variability in scattering coefficients was observed and suggests identifying precancerous lesions based on the relative change in scattering coefficients. PMID:26504630

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

    PubMed

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

    2012-12-21

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

  12. 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 cellcell junctional proteins in primary cultures of porcine stratified squamous esophageal epithelium. We used immunohistochemistry and Western analysis to monitor expression of CaSR and cellcell 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 ?-catenin from the cell membrane to the cytoplasm. Furthermore, it reduced expression of ?-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 Barretts, esophageal adenocarcinoma, squamous cell carcinoma, and eosinophilic esophagitis. Long-term activation of CaSR with CCT disrupted the cadherincatenin 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

  13. NFkB and Nrf2 in esophageal epithelial barrier function

    PubMed Central

    Chen, Hao; Fang, Yu; Li, Wenbo; Orlando, Roy C; Shaheen, Nicholas; Chen, Xiaoxin Luke

    2013-01-01

    The stratified squamous epithelium of the esophagus forms a tight protective barrier. Defects of the barrier function contribute to gastroesophageal reflux disease (GERD), which is manifested as damage to the esophageal epithelium due to exposure to the gastrointestinal refluxate. In this review, we discuss the involvement of NFkB and Nrf2 in esophageal epithelial barrier function. Understanding these molecular pathways in the esophagus may help us develop therapeutic strategies to improve clinical outcomes in patients with GERD. PMID:24790804

  14. Development, validation and implementation of an in vitro model for the study of metabolic and immune function in normal and inflamed human colonic epithelium.

    PubMed

    Pedersen, Gitte

    2015-01-01

    Ulcerative colitis (UC) and Crohn's disease (CD), collectively referred to as inflammatory bowel disease (IBD), are chronic immune disorders affecting the gastrointestinal tract. The aetiology of IBD remains an enigma, but increasing evidence suggests that the development of IBD may be triggered by a disturbance in the balance between gut commensal bacteria and host response in the intestinal mucosa. It is now known that epithelial cells have the capacity to secrete and respond to a range of immunological mediators and this suggests that these cells play a prominent role in the pathogenesis of IBD. Current knowledge about the intestinal epithelium has mainly been obtained using models based on animal cells, transformed human intestinal cell lines and isolated cells from resected colonic bowel segments. Species difference, malignant origin and confounders related to surgery, obviously make these cell models however less applicable for patophysiological studies. Consequently, there was a clear need for models of representative intestinal epithelial cells that would allow functional and dynamic studies of the differentiated human colonic epithelium in vitro. The primary purpose of this thesis was to explore and validate the optimal conditions for establishing a model based on short-term cultures of human colonic epithelial cells obtained from endoscopical biopsies. The cell cultures were accordingly used to describe the interplay between proinflammatory cytokines and colonic epithelium, with focus on alterations in viability, butyrate metabolism and secretion of a chemokine and metalloproteinases (MMP). Finally, the model was used to characterize expression and activation of receptors like toll like receptor (TLR)9 and peroxisome activated proliferators (PPAR)- known to be important players in regulation of innate and adaptive immune responses in human colonic epithelium. The results showed that it is possible to establish short-term cultures of representative, viable human colonic epithelial cells from endoscopic mucosal biopsies of patients with IBD. Short-time isolation by EGTA/EDTA from colonic biopsies allowed establishment of small scale cultures of epithelial cells which were viable and metabolic active for up to 48 hours in vitro. The cell model preserved important cellular metabolic and immunological functions of the human colonic epithelium, including the ability to oxidate butyrate, detoxificate phenolic compounds and secrete the chemokine interleukin (IL)-8 in vitro. Tumour necrosis factor (TNF)-? and interferon (IFN)-? are pro-inflammatory cytokines, which are present in increased amounts in inflamed colonic mucosa. The precise mechanisms of cytokine-mediated mucosal injury are unknown, but one might be that TNF-? and IFN-? directly impair epithelial cell function similar to effects seen on distinct target cells in other autoimmune diseases. Using the model, both cytokines were found directly to impair the viability of colonic epithelial cells and to induce secretion of IL-8 in vitro. Interestingly, the cells from inflamed IBD mucosa were less sensitive to cytokine-induced damage, which suggests that an intrinsic defense mechanism is triggered in these cells, perhaps as a result of exposure to toxic luminal factors or high local cytokine levels in vivo. TNF-? and IFN-? may also be involved in regulation of intestinal inflammation through stimulation of MMP expression and proteolytic activity. We found that colonic epithelial cells express a range of MMPs and moreover that expression of distinct MMPs is increased in cells from inflamed IBD mucosa. Using a functional peptide cleavage assay it was shown that epithelial cells secreted proteolytic active enzymes and that the functional MMP activity was increased in inflamed IBD mucosa. This suggests that colonic epithelial cells, like myofibroblasts and immune cells, may contribute to local intestinal mucosal damage, through secretion of active MMPs. Disturbance of recognition and discrimination of potentially harmful pathogens from commensals in the intestina

  15. Esophageal human beta-defensin expression in eosinophilic esophagitis

    PubMed Central

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

    2013-01-01

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

  16. Esophageal strictures and diverticula.

    PubMed

    Smith, C Daniel

    2015-06-01

    Esophageal disease and dysfunction of the lower esophageal sphincter (LES) manifesting as gastroesophageal reflux disease (GERD) particularly, is the most common of all gastrointestinal conditions impacting patients on a day-to-day basis. LES dysfunction can lead to anatomic changes to the distal esophagus, with GERD-mediated changes being benign stricture or progression of GERD to Barrett's esophagus and even esophageal cancer, and LES hypertension impairing esophageal emptying with subsequent development of pulsion esophageal diverticulum. This article details the causes, clinical presentation, workup, and treatment of esophageal stricture and epiphrenic esophageal diverticulum. Other types of esophageal diverticula (Zenker's and midesophageal) are also covered. PMID:25965138

  17. DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses

    PubMed Central

    Wong, Chao-Jen; Luo, Yanxin; Virgin, Jeffrey B; Washington, M Kay; Willis, Joseph E; Leidner, Rom S; Chak, Amitabh

    2011-01-01

    Barrett's esophagus (BE) is a metaplastic process whereby the normal stratified, squamous esophageal epithelium is replaced by specialized intestinal epithelium. Barrett's is the only accepted precursor lesion for esophageal adenocarcinoma (EAC), a solid tumor that is rapidly increasing in incidence in western countries. BE evolves into EAC through intermediate steps that involve increasing degrees of dysplasia. Current histologic criteria are quite subjective and the clinical behavior of BE is highly variable and difficult to predict using these standards. It is widely believed that molecular alterations present in BE and EAC will provide more precise prognostic and predictive markers for these conditions than the current clinical and histologic features in use. In order to further define molecular alterations that can classify unique groups of BE and EAC, we utilized methylation microarrays to compare the global gene methylation status of a collection of normal squamous, BE, BE + high-grade dysplasia (HGD), and EAC cases. We found distinct global methylation signatures, as well as differential methylation of specific genes, that discriminated these histological groups. We also noted high and low methylation epigenotypes among the BE and EAC cases. Additional validation of those CpG sites that distinguished BE from BE + HGD and EAC may lead to the discovery of useful biomarkers with potential clinical applications in the diagnosis and prognosis of BE and EAC. PMID:22139570

  18. Eosinophilic esophagitis

    PubMed Central

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

    2015-01-01

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

  19. Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Pawar, Harsh; Srikanth, Srinivas M.; Kashyap, Manoj Kumar; Sathe, Gajanan; Chavan, Sandip; Singal, Mukul; Manju, H. C.; Kumar, Kariyanakatte Veeraiah Veerendra; Vijayakumar, M.; Sirdeshmukh, Ravi; Pandey, Akhilesh; Prasad, T. S. Keshava; Gowda, Harsha; Kumar, Rekha V.

    2015-01-01

    The development of esophageal squamous cell carcinoma (ESCC) is poorly understood and the major regulatory molecules involved in the process of tumorigenesis have not yet been identified. We had previously employed a quantitative proteomic approach to identify differentially expressed proteins in ESCC tumors. A total of 238 differentially expressed proteins were identified in that study including S100 calcium binding protein A9 (S100A9) as one of the major downregulated proteins. In the present study, we carried out immunohistochemical validation of S100A9 in a large cohort of ESCC patients to determine the expression and subcellular localization of S100A9 in tumors and adjacent normal esophageal epithelia. Downregulation of S100A9 was observed in 67% (n = 192) of 288 different ESCC tumors, with the most dramatic downregulation observed in the poorly differentiated tumors (99/111). Expression of S100A9 was restricted to the prickle and functional layers of normal esophageal mucosa and localized predominantly in the cytoplasm and nucleus whereas virtually no expression was observed in the tumor and stromal cells. This suggests the important role that S100A9 plays in maintaining the differentiated state of epithelium and suggests that its downregulation may be associated with increased susceptibility to tumor formation. PMID:26788548

  20. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

    The airway epithelium functions as a barrier and front line of host defense in the lung. Apoptosis or programmed cell death can be elicited in the epithelium as a response to viral infection, exposure to allergen or to environmental toxins, or to drugs. While apoptosis can be induced via activation of death receptors on the cell surface or by disruption of mitochondrial polarity, epithelial cells compared to inflammatory cells are more resistant to apoptotic stimuli. This paper focuses on the response of airway epithelium to apoptosis in the normal state, apoptosis as a potential regulator of the number and types of epithelial cells in the airway, and the contribution of epithelial cell apoptosis in important airways diseases. PMID:22203854

  1. Esophageal cancer.

    PubMed

    Coia, L R; Sauter, E R

    1994-01-01

    Esophageal cancer is an important problem in the United States. It results in more deaths (over 10,000 annually) than rectal cancer. Furthermore, the incidence of esophageal adenocarcinoma is increasing at a rate faster than that of nearly any other cancer and the reasons for the increase are not well understood. A variety of tumor-suppressor genes (including p53, APC, DCC and Rb) and proto-oncogenes (including prad1, EGFR, c-erb-2 and TGF alpha) may be involved in the development and progression of esophageal cancer. Clinical prognostic factors include stage, Karnofsky performance status, sex, age, anatomic location of the tumor, and degree of weight loss. A new staging system based on depth of wall penetration and lymph node involvement correlates well with prognosis for patients undergoing esophagectomy. Newer staging procedures including endoscopic ultrasound as well as the use of minimally invasive surgery, such as thoracoscopy and laparoscopy, may allow accurate staging without esophagectomy. Surgical resection provides excellent palliation; however, the chance for cure with esophagectomy alone is only 10% to 20%. Adjuvant treatment with pre- or postesophagectomy radiation may improve local-regional control but does not improve survival. Nor has preoperative chemotherapy been shown to improve survival; however, it remains an active area of investigation. Multimodality therapy, namely, chemotherapy and radiation (chemoradiation), given concurrently prior to surgical resection shows promise, with one study indicating a 5-year survival of 34%. A complete pathologic response to chemoradiation correlates with improved survival. Chemoradiation has been shown to be superior to radiation as primary management of esophageal cancer. There has been no successfully completed randomized trial of surgery versus definitive radiation or chemoradiation. However, chemoradiation represents a reasonable alternative to esophagectomy in the primary management of squamous cell carcinoma of the esophagus and chemoradiation also appears to be effective in the treatment of patients with adenocarcinoma of the esophagus, offering significant palliation and a chance for long-term survival as well. Randomized studies of preoperative chemoradiation versus surgery or versus chemoradiation alone are needed. The treatment of advanced esophageal cancer must be directed toward palliation of symptoms. Newer endoscopic techniques, including the use of expansile metal stents, laser ablation, intraluminal high-dose rate brachytherapy, BICAP tumor probe, or photodynamic therapy, offer selected patients short-term palliation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7533069

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

    PubMed

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

    2013-09-13

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

  3. Validation study of the Esohisto consensus guidelines for the recognition of microscopic esophagitis (histoGERD Trial).

    PubMed

    Schneider, Nora I; Plieschnegger, Wolfgang; Geppert, Michael; Wigginghaus, Bernd; Hoess, Gabriele M; Eherer, Andreas; Wolf, Eva-Maria; Rehak, Peter; Vieth, Michael; Langner, Cord

    2014-05-01

    In patients with gastroesophageal reflux disease (GERD), histology is generally believed to be a tool of limited diagnostic value. Our study aimed to assess the prevalence of microscopic esophageal lesions as defined by the Esohisto consensus guidelines, which have proven high interobserver agreement in previous studies. In the prospective Central European multicenter histoGERD trial, we recruited 1071 individuals (576 females and 495 males; median age, 53 years; range, 15-93 years) undergoing gastroscopy for nonselected reasons. Biopsy material was systematically sampled from above and below the gastroesophageal junction. Overall, histologic diagnosis of mild and severe esophagitis was made in 423 (39.5%) and 296 (27.6%) individuals, respectively, whereas the squamous mucosa of 352 individuals (32.9%) was normal upon histology or showed only insignificant findings. Proliferative changes of the squamous epithelium, in particular basal cell layer hyperplasia, papillary elongation, and intercellular space dilation, were more common than inflammatory cell infiltration. The presence of microscopic esophagitis was associated with male sex (P = .009), patients' symptoms (P = .003), history of proton pump inhibitor intake (P < .001), and the endoscopic diagnosis of esophagitis (P < .001). Notably, among the 450 patients with no endoscopic signs of esophagitis (Los Angeles Category N), 41.8% and 17.1% were identified with mild and severe (microscopic) esophagitis, respectively, indicating higher sensitivity of histologic diagnosis. In conclusion, our data illustrate the value of histology in the workup of patients with reflux disease. We suggest that biopsies should routinely be obtained when patients undergo upper gastrointestinal endoscopy for evaluation of GERD and may particularly be beneficial in patients with nonerosive reflux disease. PMID:24746203

  4. Normalization.

    ERIC Educational Resources Information Center

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how

  5. True Intramural Esophageal Duplication Cyst.

    PubMed

    Al-Riyami, Salim; Al-Sawafi, Yaqoob

    2015-11-01

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

  6. True Intramural Esophageal Duplication Cyst

    PubMed Central

    Al-Riyami, Salim; Al-Sawafi, Yaqoob

    2015-01-01

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

  7. Engineering Airway Epithelium

    PubMed Central

    Soleas, John P.; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K.

    2012-01-01

    Airway epithelium is constantly presented with injurious signals, yet under healthy circumstances, the epithelium maintains its innate immune barrier and mucociliary elevator function. This suggests that airway epithelium has regenerative potential (I. R. Telford and C. F. Bridgman, 1990). In practice, however, airway regeneration is problematic because of slow turnover and dedifferentiation of epithelium thereby hindering regeneration and increasing time necessary for full maturation and function. Based on the anatomy and biology of the airway epithelium, a variety of tissue engineering tools available could be utilized to overcome the barriers currently seen in airway epithelial generation. This paper describes the structure, function, and repair mechanisms in native epithelium and highlights specific and manipulatable tissue engineering signals that could be of great use in the creation of artificial airway epithelium. PMID:22523471

  8. Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma.

    PubMed

    Kailasam, Aparna; Mittal, Sumeet K; Agrawal, Devendra K

    2015-08-01

    Epigenetic influences, such as DNA methylation, histone acetylation, and up-regulation/down-regulation of genes by microRNAs, change the genetic makeup of an individual without affecting DNA base-pair sequences. Indeed, epigenetic changes play an integral role in the progression from normal esophageal mucosa to Barrett's esophagus to esophageal adenocarcinoma via dysplasia-metaplasia-neoplasia sequence. Many genes involved in esophageal adenocarcinoma display hypermethylation, leading to their down-regulation. The classes of these genes include cell cycle control, DNA and growth factor repair, tumor suppressors, antimetastasis, Wnt-related genes, and proapoptotic genes. Histone acetylation in the pathophysiology of esophageal diseases has not been thoroughly investigated, and its critical role in the development of esophageal adenocarcinoma is less defined. Many microRNAs have been associated with the development of Barrett's esophagus and esophageal adenocarcinoma. Here, we critically addressed the specific steps most closely influenced by microRNAs in the progression from Barrett's esophagus to esophageal adenocarcinoma. However, microRNAs can target up to hundreds of genes, making it difficult to correlate directly with a given phenotype of the disease. Esophageal adenocarcinoma progressing from premalignant condition of Barrett's esophagus carries an extremely poor prognosis. Risk stratification for patients based on their epigenetic profiles may be useful in providing more targeted and directed treatment to patients. PMID:25388215

  9. Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

    PubMed Central

    2012-01-01

    Background Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA) were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and molecular pathways mediating ESCC development and provide information potentially useful in designing novel therapeutic interventions for this tumor type. PMID:22280838

  10. Immunologic function of dendritic cells in esophageal cancer.

    PubMed

    Yang, Wenfeng; Yu, Jinming

    2008-07-01

    Esophageal cancer is one of the frequently occurring malignant cancers. The current therapy, including surgery, chemotherapy, radiotherapy, or a combination, is only to palliate the symptoms; overall the prognosis is poor. The immunotherapy of dendritic cells for esophageal cancer is a valuable method. Dendritic cells existing in the esophageal tissues play an important role in the host's immunosurveillance against cancer as the professional antigen-presenting cells. This review concerns the immunology of dendritic cells in esophageal cancer; it describes the expression of DCs in the normal esophageal tissues and benign disease of esophagus, relations between the DCs and cancer development in esophageal cancer, and the DC-based approach to establish treatment for esophageal cancer. PMID:18080193

  11. Can We Determine Appropriate Foods to Eliminate to Treat Eosinophilic Esophagitis?

    MedlinePLUS

    ... treat Eosinophilic Esophagitis? Share | Can we determine appropriate foods to eliminate to treat Eosinophilic Esophagitis? Published Online: ... not normally present. The disease is due to food allergies in almost all pediatric patients, but standard ...

  12. Influence of Ionizing Radiation on Stromal-Epithelial Communication in Esophageal Carcinogenesis

    NASA Astrophysics Data System (ADS)

    Huff, Janice; Patel, Zarana; Grugan, Katharine; Rustgi, Anil; Cucinotta, Francis A.

    Esophageal cancer is the 6th leading cause of cancer death worldwide and is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. A connection with ionizing radiation exposure is revealed by the high excess relative risk for esophageal squamous cell carcinoma observed in the survivors of the atomic bomb detonations in Japan. Esophageal carcinomas are also seen as secondary malignancies in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely responsive to treatment. In normal epithelium, the stromal microenvironment is essential for the maintenance and modulation of cell growth and differentiation. Cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibrob-lasts (Okawa et al., Genes Dev. 2007. 21: 2788-2803). We examined how irradiation of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. These assays were conducted in modified Boyden chambers using conditioned media from irradiated fibroblasts. Our results using low LET gamma radiation showed a dose-dependent increase in migration of epithelial cells when exposed to conditioned media from irradiated vs. non-irradiated fibroblasts. We also observed enhanced invasion through a basement membrane matrix in similarly treated cells. Candidate factors that me-diate these effects were identified using antibody capture arrays, and their increased secretion in irradiated fibroblasts was confirmed using ELISAs. We are currently analyzing the effect of these individual factors on epithelial migration and invasion, as well as their influence on cell survival and DNA repair. Our current studies using high-LET radiation will elucidate radiation quality effects on these processes. These results should further our understanding of the mechanisms by which radiation impacts the tissue microenvironment and how it influences cancer development processes.

  13. 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 15-18mm. 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. PMID:26552780

  14. Expression of androgen receptor and its association with estrogen receptor and androgen receptor downstream proteins in normal/benign breast luminal epithelium.

    PubMed

    Wang, Xi; Yarid, Nicole; McMahon, Loralee; Yang, Qi; Hicks, David G

    2014-08-01

    The androgen receptor (AR) is strongly expressed in the majority of breast carcinomas, but its role in breast hormonal carcinogenesis is not clear. We believe a better knowledge of the biology of normal/benign breast tissue will be the key to understanding this process. Using standard immunohistochemical staining on consecutive sections and dual immunohistochemical labeling, we studied the expression pattern of AR and estrogen receptor (ER) in normal/benign breast luminal epithelial cells. We found that most of the AR-positive cells are also ER positive, about 10% of the cells are AR-positive only, whereas ER-positive only cells are uncommon, a distribution pattern of hormone receptor expression similar to what was revealed in invasive breast carcinomas. Whereas the expression of AR downstream proteins, such as prostate-specific antigen and gross cystic disease fluid protein, was either negative or unrelated to the AR status. We conclude that AR and ER expression status in invasive breast carcinomas reflects that of their progenitor cells in terminal duct lobular units. Our study did not reveal the expression of AR downstream proteins in normal/benign luminal epithelial cells at the regular immunohistochemistry level. PMID:24897063

  15. Expression of androgen receptor and its association with estrogen receptor and androgen receptor downstream proteins in normal/benign breast luminal epithelium.

    TOXLINE Toxicology Bibliographic Information

    Wang X; Yarid N; McMahon L; Yang Q; Hicks DG

    2014-08-01

    The androgen receptor (AR) is strongly expressed in the majority of breast carcinomas, but its role in breast hormonal carcinogenesis is not clear. We believe a better knowledge of the biology of normal/benign breast tissue will be the key to understanding this process. Using standard immunohistochemical staining on consecutive sections and dual immunohistochemical labeling, we studied the expression pattern of AR and estrogen receptor (ER) in normal/benign breast luminal epithelial cells. We found that most of the AR-positive cells are also ER positive, about 10% of the cells are AR-positive only, whereas ER-positive only cells are uncommon, a distribution pattern of hormone receptor expression similar to what was revealed in invasive breast carcinomas. Whereas the expression of AR downstream proteins, such as prostate-specific antigen and gross cystic disease fluid protein, was either negative or unrelated to the AR status. We conclude that AR and ER expression status in invasive breast carcinomas reflects that of their progenitor cells in terminal duct lobular units. Our study did not reveal the expression of AR downstream proteins in normal/benign luminal epithelial cells at the regular immunohistochemistry level.

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

    PubMed Central

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

    2012-01-01

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

  17. BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis.

    PubMed

    Jiang, Ming; Ku, Wei-Yao; Zhou, Zhongren; Dellon, Evan S; Falk, Gary W; Nakagawa, Hiroshi; Wang, Mei-Lun; Liu, Kuancan; Wang, Jun; Katzka, David A; Peters, Jeffrey H; Lan, Xiaopeng; Que, Jianwen

    2015-04-01

    Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett's intestinal differentiation; however, in mice, basal progenitor cell-specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE. PMID:25774506

  18. 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

  19. Specificity of tumor necrosis factor toxicity for human mammary carcinomas relative to normal mammary epithelium and correlation with response to doxorubicin

    SciTech Connect

    Dollbaum, C.; Creasey, A.A.; Dairkee, S.H.; Hiller, A.J.; Rudolph, A.R.; Lin, L.; Vitt, C.; Smith, H.S. )

    1988-07-01

    By using a unique short-term culture system capable of growing both normal and malignant breast epithelial tissue, human recombinant tumor necrosis factor (TNF) showed preferential cytotoxicity to malignant cells as compared to the corresponding nonmalignant cells. Most of the malignant specimens were sensitive to TNF with 13 of 18 specimens showing 90% inhibition of clonal growth (ID{sub 90}). In contrast, all 13 nonmalignant specimens tested clustered at the resistant end of the TNF response spectrum. This differential sensitivity to TNF was seen in three cases in which malignant and nonmalignant breast epithelial tissues from the same patient were studied. To investigate the mechanism of resistance to TNF by normal cells, the presence of receptors for TNF was determined. Five of six cultures showed specific binding of {sup 125}I-labeled TNF and there was no relationship between the degree of resistance and the degree of specific binding. Simultaneous comparison of tumor responsiveness to doxorubicin and TNF revealed a positive correlation in ID{sub 90} values; these results may have important implications for the clinical use of TNF in cancer patients heavily pretreated with doxorubicin.

  20. Specificity of Tumor Necrosis Factor Toxicity for Human Mammary Carcinomas Relative to Normal Mammary Epithelium and Correlation with Response to Doxorubicin

    NASA Astrophysics Data System (ADS)

    Dollbaum, Charles; Creasey, Abla A.; Dairkee, Shahnaz H.; Hiller, Alan J.; Rudolph, Alfred R.; Lin, Leo; Vitt, Charles; Smith, Helene S.

    1988-07-01

    By using a unique short-term culture system capable of growing both normal and malignant breast epithelial tissue, human recombinant tumor necrosis factor (TNF) showed preferential cytotoxicity to malignant cells as compared to the corresponding nonmalignant cells. Most of the malignant specimens were sensitive to TNF with 13 of 18 specimens showing 90% inhibition of clonal growth (ID90) by <500 units of TNF per ml of culture fluid. In contrast, all 13 nonmalignant specimens tested clustered at the resistant end of the TNF response spectrum, with ID90 values being >5000 units of TNF per ml of culture fluid. This differential sensitivity to TNF was seen in three cases in which malignant and nonmalignant breast epithelial tissues from the same patient were studied. To investigate the mechanism of resistance to TNF by normal cells, the presence of receptors for TNF was determined. Five of six cultures showed specific binding of 125I-labeled TNF and there was no relationship between the degree of resistance and the degree of specific binding. Simultaneous comparison of tumor responsiveness to doxorubicin and TNF revealed a positive correlation in ID90 values; these results may have important implications for the clinical use of TNF in cancer patients heavily pretreated with doxorubicin.

  1. Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche.

    PubMed

    Hayakawa, Yoku; Ariyama, Hiroshi; Stancikova, Jitka; Sakitani, Kosuke; Asfaha, Samuel; Renz, Bernhard W; Dubeykovskaya, Zinaida A; Shibata, Wataru; Wang, Hongshan; Westphalen, Christoph B; Chen, Xiaowei; Takemoto, Yoshihiro; Kim, Woosook; Khurana, Shradha S; Tailor, Yagnesh; Nagar, Karan; Tomita, Hiroyuki; Hara, Akira; Sepulveda, Antonia R; Setlik, Wanda; Gershon, Michael D; Saha, Subhrajit; Ding, Lei; Shen, Zeli; Fox, James G; Friedman, Richard A; Konieczny, Stephen F; Worthley, Daniel L; Korinek, Vladimir; Wang, Timothy C

    2015-12-14

    The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12(+) endothelial cells and Cxcr4(+) gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche. PMID:26585400

  2. Detection of blood group A and H-related antigens in normal and neoplastic bladder epithelium: a comparative study using monoclonal antibodies with defined fine specificities.

    PubMed Central

    Thorpe, S. J.; Abel, P.

    1991-01-01

    Three monoclonal anti-blood group H and four monoclonal anti-blood group A antibodies directed at the blood group antigens on Type 1 or Type 2 backbone structures were evaluated as immunohistochemical reagents by indirect immunofluorescence of normal and neoplastic bladder epithelia. The results were compared with fluorescence using polyclonal rabbit anti-A or H sera or Ulex europaeus lectin. The monoclonal antibodies gave less intense or more restricted immunofluorescence than the conventional reagents but showed considerable variation in the extent of their reactivities with urothelial samples from different individuals. In some cases they failed to give immunofluorescence with tissue samples known to contain the immunodominant blood group structures they recognize. In addition, hitherto unsuspected heterogeneity was revealed in the expression of the Type 2-based blood group H and A-structures in the endothelia of neighbouring small blood vessels. Images Fig. 3 Fig. 4 PMID:1707648

  3. Robotic benign esophageal procedures.

    PubMed

    Hanna, Jennifer M; Onaitis, Mark W

    2014-05-01

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

  4. [Esophageal stenting complications].

    PubMed

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

    2014-01-01

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

  5. Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis

    PubMed Central

    Cho, Jae Youn; Rosenthal, Peter; Miller, Marina; Pham, Alexa; Aceves, Seema; Sakuda, Shohei; Broide, David H

    2014-01-01

    Studies of AMCase inhibition in mouse models of lung eosinophilic inflammation have produced conflicting results with some studies demonstrating inhibition of eosinophilic inflammation and others not. No studies have investigated the role of AMCase inhibition in eosinophilic esophagitis (EoE). We have used a mouse model of egg (OVA) induced EoE to determine whether pharmacologic inhibition of AMCase with allosamidin reduced eosinophilic inflammation and remodeling in the esophagus in EoE. Administration of intra-esophageal OVA for 6 weeks to BALB/c mice induced increased levels of esophageal eosinophils, mast cells, and features of esophageal remodeling (fibrosis, basal zone hyperplasia, deposition of the extracellular matrix protein fibronectin). Administration of intraperitoneal (ip) allosamidin to BALB/c mice significantly inhibited AMCase enzymatic activity in the esophagus. Pharmacologic inhibition of AMCase with ip allosamidin inhibited both OVA induced increases in esophageal eosinophilic inflammation and OVA induced esophageal remodeling (fibrosis, epithelial basal zone hyperplasia, extracellular matrix deposition of fibronectin). This inhibition of eosinophilic inflammation in the esophagus by ip allosamidin was associated with reduced eotaxin-1 expression in the esophagus. Oral allosamidin inhibited eosinophilic inflammation in the epithelium but did not inhibit esophageal remodeling. These studies suggest that pharmacologic inhibition of AMCase results in inhibition of eosinophilic inflammation and remodeling in the esophagus in a mouse model of egg induced EoE partially through effects in the esophagus on reducing chemokines (i.e. eotaxin-1) implicated in the pathogenesis of EoE. PMID:24239745

  6. 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

  7. Current Management of Eosinophilic Esophagitis 2015.

    PubMed

    Richter, Joel E

    2016-02-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by esophageal dysfunction and eosinophilic infiltrate (?15/hpf) in the esophageal epithelium and the absence of other potential causes of eosinophilia. The prevalence is increasing and is the most common cause of solid food dysphagia in children and young adults. This article will review the diagnosis and management of EoE based on consensus conferences, systematic reviews, and meta-analysis and highlights seminal studies in our evolving treatment of this disease. However, all answers are not available and I will remark about the lessons learned in my clinical practice seeing EoE patients over the last 25 years. The complicated etiology of the complaint of dysphagia in EoE patients will be reviewed. The importance of utilizing endoscopy, biopsies, and barium esophagram to help define the 2 phenotypes (inflammatory, fibrostenosis) of EoE will be highlighted. The controversy about PPI-responsive esophageal eosinophilia will be discussed and contrasted with idiopathic EoE. Finally, the 3 treatment options for EoE (drugs, diet, dilation) will be reviewed in detail and a useful clinical management algorithm presented. PMID:26485101

  8. Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE)

    PubMed Central

    Chandramouleeswaran, Prasanna M.; Shen, Dawen; Lee, Anna J.; Benitez, Alain; Dods, Kara; Gambanga, Fiona; Wilkins, Benjamin J.; Merves, Jamie; Noah, Yuliana; Toltzis, Sarit; Yearley, Jennifer H.; Spergel, Jonathan M.; Nakagawa, Hiroshi; Malefyt, Rene deWaal; Muir, Amanda B.; Wang, Mei-Lun

    2016-01-01

    Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2-type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (≥15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control subjects, and found that TSLP expression was restricted to the differentiated suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent with these results in vivo, inducible TSLP protein secretion was higher in CaCl2 differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT) compared to undifferentiated cells of the basal phenotype, following stimulation with the TLR3 ligand poly(I:C). To determine whether food antigens could directly induce epithelial TSLP secretion, differentiated and undifferentiated primary esophageal epithelial cells from EoE and non-EoE subjects were challenged with food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced TSLP secretion in differentiated epithelial cells from both EoE and control cell lines, an effect abolished by budesonide and NF-κb inhibition. Together, our study shows that specific food antigens can trigger innate immune mediated esophageal TSLP secretion, suggesting that esophageal epithelial cells at the barrier surface may play a significant role in the pathogenesis of EoE by regulating TSLP expression. PMID:26992000

  9. Endocytoscopic observation of various esophageal lesions at 600: can nuclear abnormality be recognized?

    PubMed

    Kumagai, Y; Kawada, K; Higashi, M; Ishiguro, T; Sobajima, J; Fukuchi, M; Ishibashi, K; Baba, H; Mochiki, E; Aida, J; Kawano, T; Ishida, H; Takubo, K

    2015-04-01

    Endocytoscopy (ECS) is a novel endoscopic technique that allows detailed diagnostic examination of the gastrointestinal tract at the cellular level. We previously reported that use of ECS at 380 magnification (GIF-Y0002) allowed a pathologist to diagnose esophageal squamous cell carcinoma (ESCC) with high sensitivity (94.9%) but considerably low specificity (46.7%) because this low magnification did not reveal information about nuclear abnormality. In the present study, we used the same magnifying endoscope to observe various esophageal lesions, but employed digital 1.6-fold magnification to achieve an effective magnification of 600, and evaluated whether this improved the diagnostic accuracy in distinguishing neoplastic from non-neoplastic lesions.We examined the morphology of surface cells using vital staining with toluidine blue and compared the histological features of 40 cases, including 19 case of ESCC and 21 non-neoplastic esophageal lesions (18 cases of esophagitis, 1 case of glycogenic acanthosis, 1 case of leiomyoma, and 1 case of normal squamous epithelium). One endoscopist classified the lesions using the type classification, and we consulted one pathologist for judgment of the ECS images as 'neoplastic', 'borderline', or 'non-neoplastic'. At 600 magnification, the pathologist confirmed that nuclear abnormality became evident, in addition to the information about nuclear density provided by observation at 380. The overall sensitivity and specificity with which the endoscopist was able to predict neoplastic lesions using the type classification was 100% (19/19) and 90.5% (19/21), respectively, in comparison with values of 94.7% (18/19 cases) and 76.2% (16/21), respectively, for the pathologist using a magnification of 600. The pathologist diagnosed two non-neoplastic lesions and one case of ESCC showing an apparent increase of nuclear density with weak nuclear abnormality as 'borderline'. Among the 21 non-cancerous lesions, two cases of esophagitis that were misdiagnosed by the endoscopist were also misinterpreted as 'neoplastic' by the pathologist. We have shown, by consultation with a pathologist, that an ECS magnification of 600 (on a 19-inch monitor) is adequate for recognition of nuclear abnormality. We consider that it is feasible to diagnose esophageal neoplasms on the basis of ECS images, and that biopsy histology can be omitted if a combination of increased nuclear density and nuclear abnormality is observed. PMID:24467464

  10. Long-term outcome of esophageal myotomy for achalasia

    PubMed Central

    Liu, Jun-Feng; Zhang, Jun; Tian, Zi-Qiang; Wang, Qi-Zhang; Li, Bao-Qing; Wang, Fu-Shun; Cao, Fu-Min; Zhang, Yue-Feng; Li, Yong; Fan, Zhao; Han, Jian-Jing; Liu, Hui

    2004-01-01

    AIM: Modified Hellers myotomy is still the first choice for achalasia and the assessment of surgical outcomes is usually made based on the subjective sensation of patients. This study was to objectively assess the long-term outcomes of esophageal myotomy for achalasia using esophageal manometry, 24-hourour pH monitoring, esophageal scintigraphy and fiberoptic esophagoscopy. METHODS: From February 1979 to October 2000, 176 patients with achalasia underwent modified Hellers myotomy, including esophageal myotomy alone in 146 patients, myotomy in combination with Gallone or Dor antireflux procedure in 22 and 8 patients, respectively. Clinical score, pressure of the lower esophageal sphincter (LES), esophageal clearance rate and gastroesophageal reflux were determined before and 1 to 22 years after surgery. RESULTS: After a median follow-up of 14 years, 84.5% of patients had a good or excellent relief of symptoms, and clinical scores as well as resting pressures of the esophageal body and LES were reduced compared with preoperative values (P < 0.001). However, there was no significant difference in DeMeester score between pre- and postoperative patients (P = 0.51). Esophageal transit was improved in postoperative patients, but still slower than that in normal controls. The incidence of gastroesophageal reflux in patients who underwent esophageal myotomy alone was 63.6% compared to 27.3% in those who underwent myotomy and antireflux procedure (P = 0.087). Three (1.7%) patients were complicated with esophageal cancer after surgery. CONCLUSION: Esophageal myotomy for achalasia can reduce the resting pressures of the esophageal body and LES and improve esophageal transit and dysphagia. Myotomy in combination with antireflux procedure can prevent gastroesophageal reflux to a certain extent, but further randomized studies should be carried out to demonstrate its efficacy. PMID:14716841

  11. Distribution and ultrastructural characteristics of dark cells in squamous metaplasias of the respiratory tract epithelium. [Rats

    SciTech Connect

    Klein-Szanto, A.J.P.; Nettesheim, P.; Pine, A.; Martin, D.

    1981-05-01

    Dark epithelial basal cells were found in both carcinogen-induced and non-carcinogen-induced squamous metaplasias of the tracheal epithelium. Formaldehyde-induced squamous metaplasias exhibited 4% dark cells in the basal layer. Metaplasias induced by vitamin A deficiency and those induced by dimethylbenz(a)anthracene (DMBA) without atypia showed 18-20% basal dark cells. DMBA-induced metaplasias with moderate to severe atypia exhibited 50% basal dark cells. The labeling index of basal cells in metaplastic epithelia, regardless of the inducing agent, was 16-18%, ie, the same as that of the normal esophageal stratified squamous epithelium. The percentage of labeled dark basal cells per total dark cell population was approximately 19% in the non-carcinogen-induced metaplasias and in the DMBA-induced metaplasias without atypia. In the atypical metaplasias induced by DMA this percentage increased to 26. On the basis of ultrastructural observations, five types of dark epithelial cells could be distinguished in the metaplastic epithelia. Each type of squamous metaplasia could thus be recognized by a determined numerical distribution of dark cells in the basal layer and a specific pattern of distribution of the ultrastructurally defined dark cell categories.

  12. Recent advances in the treatment of eosinophilic esophagitis

    PubMed Central

    Schroeder, Shauna; Atkins, Dan; Furuta, Glenn T

    2013-01-01

    First described nearly 20 years ago, eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus characterized by eosinophilic infiltration of the esophageal epithelium. Over 50% of the current literature on EoE has been published in the last 3 years, signaling both a rising incidence and increased recognition of this disorder. Treatment options available for patients with EoE include dietary management and/or pharmacologic therapy. An individualized approach to treatment is preferred, with an emphasis on patientparental preference. The objective of this article is to discuss the current and future treatment options for EoE. PMID:20979557

  13. Diet and esophageal disease

    PubMed Central

    Dawsey, Sanford M.; Fagundes, Renato B.; Jacobson, Brian C.; Kresty, Laura A.; Mallery, Susan R.; Paski, Shirley; van den Brandt, Piet A.

    2014-01-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on macronutrients, dietary patterns, and risk of adenocarcinoma in Barretts esophagus; micronutrients, trace elements, and risk of Barretts esophagus and esophageal adenocarcinoma; the role of mate consumption in the development of squamous cell carcinoma; the relationship between energy excess and development of esophageal adenocarcinoma; and the nutritional management of the esophageal cancer patient. PMID:25266021

  14. Integrin Expression in Esophageal Squamous Cell Carcinoma: Loss of the Physiological Integrin Expression Pattern Correlates with Disease Progression

    PubMed Central

    Vay, Christian; Hosch, Stefan B.; Stoecklein, Nikolas H.; Klein, Christoph A.; Vallbhmer, Daniel; Link, Bjrn-Christian; Yekebas, Emre F.; Izbicki, Jakob R.; Knoefel, Wolfram T.; Scheunemann, Peter

    2014-01-01

    The integrins are a family of heterodimeric transmembrane signaling receptors that mediate the adhesive properties of epithelial cells affecting cell growth and differentiation. In many epithelial malignancies, altered integrin expression is associated with tumor progression and often correlates with unfavorable prognosis. However, only few studies have investigated the role of integrin expression in esophageal squamous cell carcinoma (ESCC). Using a novel quantifying immunofluorescence-staining assay, we investigated the expression of the integrins ?2?1, ?3?1, ?6?1, and ?6?4 in primary ESCC of 36 patients who underwent surgical resection. Magnitude and distribution of expression were analyzed in primary tumor samples and autologous esophageal squamous epithelium. The persistence of the physiologically polarized expression of the subunits ?6, ?1, and ?4 in the tumor tissue was significantly associated with prolonged relapse-free survival (p?=?0.028, p?=?0.034, p?=?0.006). In contrast, patients with reduced focal ?6 expression at the tumor invasion front shared a significantly shortened relapse-free survival compared to patients with strong ?6 expression at their stromal surfaces, as it was regularly observed in normal esophageal epithelium (p?=?0.001). Multivariate regression analysis identified the maintenance of strong ?6 immunoreactivity at the invasion front as an independent prognostic factor for increased relapse-free and disease-specific survival (p?=?0.003; p?=?0.003). Our findings suggest that alterations in both pattern and magnitude of integrin expression may play a major role in the disease progression of ESCC patients. Particularly, the distinct expression of the integrins ?6?4 and ?6?1 at the invasion front as well as the maintenance of a polarized integrin expression pattern in the tumor tissue may serve as valuable new markers to assess the aggressiveness of ESCC. PMID:25398092

  15. Esophageal lichen planus*

    PubMed Central

    de Oliveira, Janine Pichler; Uribe, Natalia Caballero; Abulafia, Luna Azulay; Quintella, Leonardo Pereira

    2015-01-01

    Lichen planus is a chronic inflammatory disease that affects the skin, mucous membranes, nails and scalp. Esophageal lichen planus is a rarely reported manifestation of lichen planus, presenting itself commonly in middle-aged women, with symptoms such as dysphagia. We report a case of esophageal lichen planus in a 54-year-old woman associated with oral, cutaneous and ungual lichen planus. Although lichen planus is a disorder well known by dermatologists, reports of esophageal lichen planus are rare in dermatologic literature. The esophageal lichen planus is little known and underdiagnosed, with a significant delay between the onset of symptoms and diagnosis. PMID:26131872

  16. Ductal barriers in mammary epithelium

    PubMed Central

    Owens, Mark B; Hill, Arnold DK; Hopkins, Ann M

    2013-01-01

    Tissue barriers play an integral role in the biology and pathobiology of mammary ductal epithelium. In normal breast physiology, tight and adherens junctions undergo dynamic changes in permeability in response to hormonal and other stimuli, while several of their proteins are directly involved in mammary tumorigenesis. This review describes first the structure of mammary ductal epithelial barriers and their role in normal mammary development, examining the cyclical changes in response to puberty, pregnancy, lactation and involution. It then examines the role of adherens and tight junctions and the participation of their constituent proteins in mammary tumorigenic functions such as migration, invasion and metastasis. Finally, it discusses the potential of these adhesion proteins as both prognostic biomarkers and potential therapeutic targets in breast cancer. PMID:24665412

  17. Bleeding esophageal varices

    MedlinePLUS

    ... if the veins break open. Any type of chronic liver disease can cause esophageal varices. Varices can also occur ... People with chronic liver disease and esophageal varices may have no symptoms. If there is only a small amount of bleeding, the only ...

  18. Esophageal cyst in the duodenum of a foal.

    PubMed

    Loynachan, Alan T

    2014-03-01

    A 21-day-old Thoroughbred colt was euthanized following a history of recurrent colic. A 4.5 cm in diameter, occlusive, submucosal cyst was identified in the duodenum at necropsy. Histologically, the cyst was surrounded by a smooth muscle wall and was lined by both squamous and attenuated cuboidal to columnar epithelium. A diagnosis of an esophageal cyst was made based on the gross and histologic findings. PMID:24595302

  19. The expression of ?-catenin in esophageal squamous cell carcinoma and its correlations with prognosis of patients.

    PubMed

    Zhang, Jun-Yi; Bai, Chun-Ying; Bai, Yu-Qin; Zhang, Jing-Yi; Wu, Zhi-Yong; Wang, Shao-Hong; Xu, Xiu-E; Wu, Jian-Yi; Zhu, Ying; Rui, Yun; Li, En-Min; Xu, Li-Yan

    2014-10-01

    As a member of the catenin family, expression of ?-catenin and its clinical implication in numerous tumors remain unclear. In the present study, expression of ?-catenin in esophageal squamous cell carcinoma (ESCC) and its correlations with patient prognosis were explored. We detected the expression of ?-catenin, by immunohistochemistry, in ESCC tissues from 299 cases and analyzed the correlation between ?-catenin expression and patient clinicopathological features. Compared with a lack of expression in adjacent normal esophageal epithelium (0%, 0/47), the frequency of ?-catenin protein was increased in ESCC tissues to 41.5% (124/299, P < .001) and expression correlated with TNM stage and lymph node metastasis (P = .025 and .019, respectively). Furthermore, Kaplan-Meier survival analysis revealed that patients with high ?-catenin expression had shorter survival than patients with low expression (P = .010), and multivariate Cox analysis revealed that high ?-catenin expression was also an independent prognostic factor (P = .001). In transwell assays, migration of ESCC cells was enhanced by ?-catenin overexpression, whereas proliferation of ESCC cells was unchanged. Together, our results suggest that ?-catenin acts as an oncoprotein when overexpressed in ESCC, and its expression is associated with poor prognosis and malignant cell behavior. PMID:25090917

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

    PubMed

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

    2012-01-01

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

  1. LINE-1 expression and retrotransposition in Barrett's esophagus and esophageal carcinoma.

    PubMed

    Doucet-O'Hare, Tara T; Rodi?, Nemanja; Sharma, Reema; Darbari, Isha; Abril, Gabriela; Choi, Jungbin A; Young Ahn, Ji; Cheng, Yulan; Anders, Robert A; Burns, Kathleen H; Meltzer, Stephen J; Kazazian, Haig H

    2015-09-01

    Barrett's esophagus (BE) is a common disease in which the lining of the esophagus transitions from stratified squamous epithelium to metaplastic columnar epithelium that predisposes individuals to developing esophageal adenocarcinoma (EAC). We hypothesized that BE provides a unique environment for increased long-interspersed element 1 (LINE-1 or L1) retrotransposition. To this end, we evaluated 5 patients with benign BE, 5 patients with BE and concomitant EAC, and 10 additional patients with EAC to determine L1 activity in this progressive disease. After L1-seq, we confirmed 118 somatic insertions by PCR in 10 of 20 individuals. We observed clonal amplification of several insertions which appeared to originate in normal esophagus (NE) or BE and were later clonally expanded in BE or in EAC. Additionally, we observed evidence of clonality within the EAC cases; specifically, 22 of 25 EAC-only insertions were present identically in distinct regions available from the same tumor, suggesting that these insertions occurred in the founding tumor cell of these lesions. L1 proteins must be expressed for retrotransposition to occur; therefore, we evaluated the expression of open reading frame 1 protein (ORF1p), a protein encoded by L1, in eight of the EAC cases for which formalin-fixed paraffin embedded tissue was available. With immunohistochemistry, we detected ORF1p in all tumors evaluated. Interestingly, we also observed dim ORF1p immunoreactivity in histologically NE of all patients. In summary, our data show that somatic retrotransposition occurs early in many patients with BE and EAC and indicate that early events occurring even in histologically NE cells may be clonally expanded in esophageal adenocarcinogenesis. PMID:26283398

  2. LINE-1 expression and retrotransposition in Barretts esophagus and esophageal carcinoma

    PubMed Central

    Doucet-O'Hare, Tara T.; Rodi?, Nemanja; Sharma, Reema; Darbari, Isha; Abril, Gabriela; Choi, Jungbin A.; Young Ahn, Ji; Cheng, Yulan; Anders, Robert A.; Burns, Kathleen H.; Meltzer, Stephen J.; Kazazian, Haig H.

    2015-01-01

    Barretts esophagus (BE) is a common disease in which the lining of the esophagus transitions from stratified squamous epithelium to metaplastic columnar epithelium that predisposes individuals to developing esophageal adenocarcinoma (EAC). We hypothesized that BE provides a unique environment for increased long-interspersed element 1 (LINE-1 or L1) retrotransposition. To this end, we evaluated 5 patients with benign BE, 5 patients with BE and concomitant EAC, and 10 additional patients with EAC to determine L1 activity in this progressive disease. After L1-seq, we confirmed 118 somatic insertions by PCR in 10 of 20 individuals. We observed clonal amplification of several insertions which appeared to originate in normal esophagus (NE) or BE and were later clonally expanded in BE or in EAC. Additionally, we observed evidence of clonality within the EAC cases; specifically, 22 of 25 EAC-only insertions were present identically in distinct regions available from the same tumor, suggesting that these insertions occurred in the founding tumor cell of these lesions. L1 proteins must be expressed for retrotransposition to occur; therefore, we evaluated the expression of open reading frame 1 protein (ORF1p), a protein encoded by L1, in eight of the EAC cases for which formalin-fixed paraffin embedded tissue was available. With immunohistochemistry, we detected ORF1p in all tumors evaluated. Interestingly, we also observed dim ORF1p immunoreactivity in histologically NE of all patients. In summary, our data show that somatic retrotransposition occurs early in many patients with BE and EAC and indicate that early events occurring even in histologically NE cells may be clonally expanded in esophageal adenocarcinogenesis. PMID:26283398

  3. High prevalence of esophageal dysmotility in asymptomatic obese patients

    PubMed Central

    Ct-Daigneault, Justin; Leclerc, Pierre; Joubert, Josette; Bouin, Mickael

    2014-01-01

    BACKGROUND: Obesity is an important health problem affecting >500 million people worldwide. Esophageal dysmotility is a gastrointestinal pathology associated with obesity; however, its prevalence and characteristics remain unclear. Esophageal dysmotilities have a high prevalence among obese patients regardless of gastrointestinal symptoms. OBJECTIVE: To identify the prevalence of esophageal dysmotility among obese patients. The secondary goals were to characterize these pathologies in obese patients and identify risk factors. METHOD: A prospective study from January 2009 to March 2010 at the University of Montreal Hospital Centre (Montreal, Quebec) was performed. Every patient scheduled for bariatric surgery underwent preoperatory esophageal manometry and was included in the study. Manometry was performed according to a standardized protocol with the following measures: superior esophageal sphincter coordination and release during deglutition; esophageal body presence, propagation, length, amplitude and type of esophageal waves of contraction; lower esophageal sphincter localization, tone, release, intragastic pressure and intraesophageal pressure. All reference values were those used in the digestive motility laboratory. A gastrointestinal symptoms questionnaire was completed on the day manometry was performed. Chart reviews were performed to identify comorbidities and treatments that could influence the results. RESULTS: A total of 53 patients were included (mean [ SD] age 4310 years; mean body mass index 467 kg/m2; 70% female). Esophageal manometry revealed dysmotility in 51% (n=27) of the patients. This dysmotility involved the esophageal body in 74% (n=20) of the patients and the inferior sphincter in 11% (n=3). Mixed dysmotility (body and inferior sphincter) was found in 15% (n=4) of cases. The esophageal body dysmotilities were hypomotility in 85% (n=23) of the patients, either from insignificant waves (74% [n=20]), nonpropagated waves (11% [n=3]) or low-amplitude waves (33% [n=9]). Gastroesophageal symptoms were found in 66% (n=35) of obese patients, including heartburn (66% [n=23]), regurgitation (26% [n=9]), dysphagia (43% [n=15]), chest pain (6% [n=2]) and dyspepsia (26% [n=9]). Among symptomatic patients, 51% (n=18) had normal manometry and 49% (n=17) had abnormal manometry (statistically nonsignificant). Among asymptomatic patients (n=18), 44% (n=8) had normal manometry and 56% (n=10) had abnormal manometry (statistically nonsignificant). Furthermore, no statistical differences were found between the normal manometry group and the abnormal manometry group with regard to medication intake or comorbidities. CONCLUSION: Esophageal dysmotilities had a high prevalence in obese patients. Gastrointestinal symptoms cannot predict the presence of esophageal dysmotility. Hypomotility of the esophageal body is the most common dysmotility, especially from the absence of significant waves. PMID:24945185

  4. Quantitative analysis of disturbed cell maturation in dysplastic lesions of the respiratory tract epithelium

    SciTech Connect

    Klein-Szanto, A.J.P.; Nettesheim, P.; Topping, D.C.; Olson, A.C.

    1980-01-01

    Autoradiographic patterns of (/sup 3/H)thymidine incorporation, nuclear/cytoplasmic ratios (N/C), and the percentage of dark epithelial cells were analyzed in a group of epithelial lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in rat tracheal transplants. It was found that similar lesions of different age exhibit the same labeling indices (LIs), therefore the lesions of different age were subsequently pooled in the following groups and studied by high resolution light microscopic autoradiography: squamous metaplasia without or with only mild atypia, squamous metaplasia with moderate atypia, squamous metaplasia with severe atypia, carcinoma in situ, and microinvasive carcinoma. Normal tracheal and esophageal epithelia were also analyzed. Gradients of increasing N/C (nucleus-cytoplasm ratios) values could be observed as the lesions increased in severity, especially in the middle and surface layers (e.g., in the surface layer regular metaplasia N/C = 0.08, squamous metaplasia with moderate atypia N/C = 0.26, and carcinoma in situ N/C = 0.50). Dark cells were absent in the normal esophageal epithelium, were present in moderate numbers in the basal layer of regular squamous metaplasia (18%), and increased markedly in the atypical epithelial lesions (approximately 50% in the atypical squamous metaplasias and 70% in carcinoma in situ). In the suprabasal layer dark cells increased from 3% in squamous metaplasia with moderate atypia to 28% in metaplasia with severe atypia and 56% in carcinoma in situ. The results confirm in a quantitative fashion that disturbances of cell maturation and cell proliferation are key features of dysplastic lesions induced by chemical carcinogens, and suggest the use of objective parameters for evaluation and classification of preneoplastic alterations.

  5. Gastroesophageal reflux activates the NF-?B pathway and impairs esophageal barrier function in mice

    PubMed Central

    Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

    2013-01-01

    The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-?B pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-?B target genes. Overexpression of NF-?B subunits (p50 and p65) and NF-?B target genes (matrix metalloproteinases-3 and -9, IL-1?, IL-6, and IL-8) confirmed activation of the NF-?B pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-?B inhibitor, BAY 11-7085 (20 mgkg?1day?1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-?B-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-?B pathway and impairs esophageal barrier function in mice and that targeting the NF-?B pathway may strengthen esophageal barrier function against reflux. PMID:23639809

  6. Esophageal cancer in Iran.

    PubMed

    Ghavamzadeh, A; Moussavi, A; Jahani, M; Rastegarpanah, M; Iravani, M

    2001-04-01

    Esophageal cancer is among the 10 most frequent cancers in the world. Iran is one of the known areas with a high incidence of esophageal cancer. Most of the patients in Iran have been reported from the north and northeast regions of the country. In one survey by the Iran Cancer Institute, 9% of all cancers and 27% of gastrointestinal cancers were esophageal carcinoma. The male to female ratio was 1.7/1. The distal portion of the esophagus is involved more often than other parts. Consumption of wheat flour, exposure to residues from opium pipes, drinking hot tea, and chewing nass (a mixture of tobacco, lime, ash, and other ingredients) are the suspect etiologic agents for esophageal cancer in Iran. Dysphagia, weight loss, anorexia, abdominal pain, and odynophagia are the common symptoms and signs of Iranian patients with esophageal cancer. For clinical staging, chest computed tomographic scanning is performed. Adenocarcinoma of the esophagus is not as common in Iran as in western countries. Public education, nutritional support, and eradication of opium addiction may decrease the morbidity and mortality that result from esophageal cancer. Surgery has traditionally been the mainstay of esophageal cancer treatment in Iran. Radiotherapy is mainly used postoperatively. The usual combination chemotherapy regimen is cisplatin plus flurouracil (5-Fu). Semin Oncol 28:153-157. PMID:11301377

  7. [Is an esophageal transit scintigram necessary in patients with gastroesophageal reflux?].

    PubMed

    T?ranu, D; Oproiu, C; Aposteanu, G; Jovin, G; Murgoci, P; Timi?, E; Oproiu, A

    1989-01-01

    Efficient esophageal clearance has an important defence role in the pathogenesis of the gastroesophageal reflux disease (GERD). Many GERD patients have esophageal disturbances associated with or secondary to reflux, producing delayed clearance. This delay exposes the esophageal mucosa to the reflux acid content. To determine esophageal transit we scanned the esophageal transit of a 15 ml bolus containing colloidal 300/cCi 99m Tc. The esophageal transit was calculated in seconds according to formula E.T. = T 1/2 x 5. The study included 74 GERD patients. The following investigations were carried out in all the cases: esophageal X-ray, GER scintigram, endoscopy, esophageal biopsy, Bernstein test and esophageal transit scintigram. Endoscopy revealed lesions of the esophagus (of 1st, 2nd and 3rd degree) in 39 patients, Barrett syndrome in 8 cases and normal in 27. Esophageal transit scanning was normal in 18 cases (24%), and prolonged in 56 cases (76%). Only 7 (39%) of the 18 patients with a normal transit presented lesions of the mucosa, the latter being more frequent in patients with a prolonged transit, i.e. 40 of 56 patients (71.5%). The mean value of the transit in different degrees of esophagitis (I, II, III) and Barrett syndrome were: 12.73 +/- 5.36; 13.30 +/- 7.90; 10.35 +/- 5.78; 17.25 +/- 11.17. In conclusion esophageal transit scanning is a useful test in GERD patients as it has a prognostic value. A prolonged esophageal transit is frequently associated with lesions, the more severe the slower is the transit. Moreover the test may indicate certain drugs acting upon the esophageal motor disturbances. PMID:2573947

  8. Relationships between Micro-Vascular and Iodine-Staining Patterns in the Vicinity of the Tumor Front of Superficial Esophageal Squamous Carcinoma

    PubMed Central

    Ohta, Shunsuke; Kawada, Kenro; Swangsri, Jirawat; Fujiwara, Naoto; Saito, Katsumasa; Fujiwara, Hisashi; Ryotokuji, Tairo; Okada, Takuya; Miyawaki, Yutaka; Tohkairin, Yutaka; Nakajima, Yasuaki; Kumagai, Youichi; Nagai, Kagami; Ito, Takashi; Eishi, Yoshinobu; Kawano, Tatsuyuki

    2015-01-01

    Objective The aim of the present study was to clarify differences between micro-vascular and iodine-staining patterns in the vicinity of the tumor fronts of superficial esophageal squamous cell carcinomas (ESCCs). Methods Ten consecutive patients with ESCCs who were treated by endoscopic submucosal dissection (ESD) were enrolled. At the edge of the iodine-unstained area, we observed 183 sites in total using image-enhanced magnifying endoscopy. We classified the micro-vascular and iodine-staining patterns into three types: Type A, in which the line of vascular change matched the border of the iodine-unstained area; Type B, in which the border of the iodine-unstained area extended beyond the line of vascular change; Type C, in which the line of vascular change extended beyond the border of the iodine-unstained area. Then, by examining histopathological sections, we compared the diameter of intra-papillary capillary loops (IPCLs) in cancerous areas and normal squamous epithelium. Results We investigated 160 sites that the adequate quality of pictures were obtained. There was no case in which the line of vascular change completely matched the whole circumference of the border of an iodine-unstained area. Among the 160 sites, type A was recognized at 76 sites (47.5%), type B at 79 sites (49.4%), and type C at 5 sites (3.1%). Histological examination showed that the mean diameter of the IPCLs in normal squamous epithelium was 16.23.7?m, whereas that of IPCLs in cancerous lesions was 21.04.4?m. Conclusions The development of iodine-unstained areas tends to precede any changes in the vascularity of the esophageal surface epithelium. PMID:26301414

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

    ClinicalTrials.gov

    2016-03-31

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

  10. Esophageal Cancer Prevention

    MedlinePLUS

    ... the type of cells that become malignant (cancerous): Squamous cell carcinoma : Cancer that begins in squamous cells , the thin, ... chance of developing esophageal cancer increases with age. Squamous cell carcinoma of the esophagus is more common in blacks ...

  11. Esophageal stricture - benign

    MedlinePLUS

    ... the esophagus. These may include household cleaners, lye, disc batteries, or battery acid. Treatment of esophageal varices ... to prevent the stricture from narrowing again. Proton pump inhibitors (acid-blocking medicines) can keep a peptic ...

  12. 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

  13. Methylation in esophageal carcinogenesis

    PubMed Central

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

    2006-01-01

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

  14. [Congenital Esophageal Atresia].

    PubMed

    Suzuki, Makoto; Kuwano, Hiroyuki

    2015-07-01

    In this report, we describe the esophageal atresia in terms of current surgical management on the basis of our experience and literatures. Traditionally, infants with esophageal atresia have presented shortly after birth because of an inability to pass an orogastric tube, respiratory distress, or an inability to tolerate feeding. And also, an isolated trachea-esophageal fistula (TEF) usually cases coughing, recurrent pneumonia, or choking during feedings. To ignore these symptoms is to risk a delayed diagnosis. The condition may be associated with other major congenital anomalies such as those seen in the vertebral, anal, cardiac, tracheo-esophageal, renal/radial (VACTER) association, or it may be an isolated defect. Therapeutic strategies for esophageal atresia are a prevention of pulmonary complication by TEF closing and an early establishment of enteral alimentation. We promptly repair healthy infants without performing a gastrostomy and delay repair in infants with high-risk factors such as associated severe cardiac anomaly and respiratory insufficiency. Esophageal atresia has been classically approached through a thoracotomy. The disadvantages of such a thoracotomy have been recognized for a long time, for example winged scapula, elevation of fixation of shoulder, asymmetry of the chest wall, rib fusion, scoliosis, and breast and pectoral muscle maldevelopment. To avoid such disadvantages, thoracoscopic repair was recently reported. PMID:26197921

  15. Persistent disruption of ciliated epithelium following paediatric lung transplantation.

    PubMed

    Thomas, Biju; Aurora, Paul; Spencer, Helen; Elliott, Martin; Rutman, Andrew; Hirst, Robert A; O'Callaghan, Christopher

    2012-11-01

    It is unclear whether ciliary function following lung transplantation is normal or not. Our aim was to study the ciliary function and ultrastructure of epithelium above and below the airway anastomosis and the peripheral airway of children following lung transplantation. We studied the ciliary beat frequency (CBF) and beat pattern, using high speed digital video imaging and ultrastructure by transmission electron microscopy, of bronchial epithelium from above and below the airway anastomosis and the peripheral airway of 10 cystic fibrosis (CF) and 10 non-suppurative lung disease (NSLD) paediatric lung transplant recipients. Compared to epithelium below the anastomosis, the epithelium above the anastomosis in the CF group showed reduced CBF (median (interquartile range): 10.5 (9.0-11.4) Hz versus 7.4 (6.4-9.2) Hz; p<0.01) and increased dyskinesia (median (IQR): 16.5 (12.9-28.2)% versus 42.2 (32.6-56.4)%; p<0.01). In both CF and NSLD groups, compared with epithelium above the anastomosis, the epithelium below the anastomosis showed marked ultrastructural abnormalities (median duration post-transplant 7-12 months). Ciliary dysfunction is a feature of native airway epithelium in paediatric CF lung transplant recipients. The epithelium below the airway anastomosis shows profound ultrastructural abnormalities in both CF and NSLD lung transplant recipients, many months after transplantation. PMID:22523358

  16. Altered esophageal histamine receptor expression in Eosinophilic Esophagitis (EoE): implications on disease pathogenesis.

    PubMed

    Merves, Jamie; Chandramouleeswaran, Prasanna Modayur; Benitez, Alain J; Muir, Amanda B; Lee, Anna J; Lim, Diana M; Dods, Kara; Mehta, Isha; Ruchelli, Eduardo D; Nakagawa, Hiroshi; Spergel, Jonathan M; Wang, Mei-Lun

    2015-01-01

    Eosinophilic Esophagitis (EoE) is a chronic allergic disorder, whose pathobiology is incompletely understood. Histamine-producing cells including mast cells and basophils have been implicated in EoE. However, very little is currently known about the role of histamine and histamine receptor (HR) expression and signaling in the esophageal epithelium. Herein, we characterized HR (H1R, H2R, H3R, and H4R) expression in human esophageal biopsies and investigate the role of histamine signaling in inducible cytokine expression in human esophageal epithelial cells in vitro. HR expression was quantified in esophageal biopsies from non-EoE control (N = 23), inactive EoE (<15 eos/hpf, N = 26) and active EoE (>15 eos/hpf, N = 22) subjects using qRT-PCR and immunofluorescent localization. HR expression and histamine-mediated cytokine secretion were evaluated in human primary and telomerase-immortalized esophageal epithelial cells. H1R, H2R, and H4R expression were increased in active EoE biopsies compared to inactive EoE and controls. H2R was the most abundantly expressed receptor, and H3R expression was negligible in all 3 cohorts. Infiltrating eosinophils expressed H1R, H2R, and H4R, which contributed to the observed increase in HR in active subjects. H1R and H2R, but not H3R or H4R, were constitutively expressed by primary and immortalized cells, and epithelial histamine stimulation induced GM-CSF, TNFα, and IL-8, but not TSLP or eotaxin-3 secretion. Epithelial priming with the TLR3 ligand poly (I:C) induced H1R and H2R expression, and enhanced histamine-induced GM-CSF, TNFα, and IL-8 secretion. These effects were primarily suppressed by H1R antagonists, but unaffected by H2R antagonism. Histamine directly activates esophageal epithelial cytokine secretion in vitro in an H1R dependent fashion. However, H1R, H2R and H4R are induced in active inflammation in EoE in vivo. While systemic antihistamine (anti-H1R) therapy may not induce clinical remission in EoE, our study suggests that further study of histamine receptor signaling in EoE is warranted and that targeting of additional histamine receptors may lead to novel treatment strategies for this important disease. PMID:25723478

  17. Esophageal Atresia and Tracheoesophageal Fistula

    MedlinePLUS

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

  18. Achalasia and Esophageal Motility Disorders

    MedlinePLUS

    ... and Esophageal Surgery A Website Presented by Cardiothoracic Surgeons Committed to Improving Patient Care Menu Main menu ... and Esophageal Surgery A website presented by cardiothoracic surgeons committed to improving patient care Footer menu English | ...

  19. Gastroesophageal scintigraphy and endoscopy in the diagnosis of esophageal reflux and esophagitis

    SciTech Connect

    Fung, W.P.; Van der Schaaf, A.; Grieve, J.C.

    1985-04-01

    The value of gastroesophageal (G/E) scintigraphy in the diagnosis of gastroesophageal reflux was assessed in 51 subjects, who presented with heartburn and had endoscopic evidence of reflux esophagitis. G/E scintigraphy was done using /sup 99m/Tc sulfur-colloid in acidified orange juice. The G/E reflux index was calculated according to previous reports. The mean (+/- SD) G/E reflux index in 18 patients with severe esophagitis and 30 patients with moderate esophagitis were 1.6% (+/- 1.5) and 3.2% (+/- 5.0), respectively. The mean G/E reflux index in 14 control subjects was 2.4% (+/- 1.1). There was no significant difference between the esophagitis and control groups. Furthermore, if 4% was taken as upper limit of normal, this will include almost all the esophagitis patients and controls. It is concluded that the G/E reflux index based on G/E scintigraphy is of little value in the diagnosis of G/E reflux.

  20. 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

  1. Tenascin-C, a Prognostic Determinant of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Lin, Zhen-Hua; Lee, Hak-Min; Xuan, Yan-Hua; Cui, Yan; Kim, Seok-Hyung

    2016-01-01

    Background Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC). Methods In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs) were also determined. Results Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001). Tenascin-C expression in ESCC stromal fibroblasts was associated with patient’s age, tumor (pT) stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM) population, cancer recurrence, and hypoxia inducible factor1α (HIF1α) expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS). In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor α (PDGFRα), PDGFRβ, and smooth muscle actin (SMA) expression. The 5-year OS and DFS rates were remarkably lower in patients with positive expressions of both Tenascin-C and PDGFRα (p < 0.001), Tenascin-C and PDGFRβ (p < 0.001), Tenascin-C and SMA (p < 0.001), Tenascin-C and fibroblast activation protein (FAP) (p < 0.001), and Tenascin-C and fibroblast-stimulating protein-1 (FSP1) (p < 0.001) in ESCC stromal fibroblasts than in patients with negative expressions of both Tenascin-C and one of the abovementioned CAF markers. Conclusion Our results show that Tenascin-C is a reliable and significant prognostic factor in ESCC. Tenascin-C may thus be a potent ESCC therapeutic target. PMID:26731558

  2. Esophagitis of likely traumatic origin in newborns.

    PubMed

    Deneyer, M; Goossens, A; Pipeleers-Marichal, M; Hauser, B; Blecker, U; Sacre, L; Vandenplas, Y

    1992-07-01

    We describe 17 full-term newborns presenting with vague symptoms related to the upper gastrointestinal tract (anorexia, poor feeding, retching, regurgitation, and incessant crying) during their stay in the maternity unit. After an esophagogastroduodenoscopy performed between days 2 and 5 of life, the babies could clearly be divided into two groups. Twelve babies (group 1) had an extremely severe esophagitis (circular ulcerations), without gastroduodenitis. In the remaining five babies (group 2), the upper gastrointestinal tract was unaffected. Allergic, infectious, metabolic, and toxic etiologies were excluded. Esophageal pH monitoring data were within normal ranges in all. All babies of group 1 were treated as follows: prone anti-Trendelenburg position, cisapride, and cimetidine syrup. Symptoms and lesions disappeared within 48-72 h. Reendoscopy after 72 h showed an almost normal esophagus with greatly improved histology. These observations highlight four points of interest: (a) the existence of an extremely severe ulcerative esophagitis in apparently healthy newborns, (b) the very rapid clinical and histological recovery, (c) the difficulties in predicting esophagitis on clinical grounds, and (d) the mysterious origin despite thorough assessment. The distribution of the lesions (more severe in the upper esophagus), the early onset (almost at birth), the very rapid healing, and the absence of gastric and duodenal lesions are in favor of a possible "traumatic" origin (pharyngeal, esophageal, and gastric suction at birth). Finally, because the condition described is transient, questions arise regarding the necessity of treatment, and we currently do not recommend overtreating newborns presenting with similar symptoms and/or endoscopic findings. PMID:1403453

  3. ZNF282 (Zinc finger protein 282), a novel E2F1 co-activator, promotes esophageal squamous cell carcinoma.

    PubMed

    Yeo, So-Young; Ha, Sang Yun; Yu, Eun Ji; Lee, Keun-Woo; Kim, Jeong Hoon; Kim, Seok-Hyung

    2014-12-15

    Zinc finger protein 282 (ZNF282) is a newly identified transcription factor and little is known about its expression and function. Originally, ZNF282 is known to bind U5RE (U5 repressive element) of HLTV-1 (human T cell leukemia virus type 1) with a repressive effect. Recently we reported that ZNF282 functions as an estrogen receptor co-activator and plays an essential role in breast tumorigenesis. Although these results suggest the possible role of ZNF282 in cancers, clinical significance and function of ZNF282 are completely unknown in most of cancers. Here we found that ZNF282 was frequently overexpressed in esophageal squamous cell carcinoma (ESCC) (n=165) compared with normal esophageal epithelium and its overexpression was correlated with adverse clinical outcome. Multivariate survival analysis indicated that ZNF282 expression was an independent prognostic predictor for poor survival in ESCC (HR: 2.56 (95% CI 1.54-4.26), p<0.001). In addition, depletion of ZNF282 inhibited the cell cycle progression, migration, and invasion of ESCC cells and reduced the tumorigenicity of ESCC xenograft in nude mouse. We further showed that ZNF282 is required for E2F1-mediated gene expression in ESCC cells. Thus, ZNF282 is E2F1 co-activator involved in ESCC and elevated expression of ZNF282 is an independent adverse prognostic factor in ESCC. PMID:25373738

  4. Expression and clinical significance of Tiam1 gene in esophageal carcinoma

    PubMed Central

    Wu, Qi-Yong; Wang, Yong; Tong, Ji-Chun; Zhang, Ming; Zhang, Ke

    2015-01-01

    Objective: To investigate the relationship between Tiam1 gene expression and the invasion and metastasis of esophageal cancer. Methods: By RT-PCR technique, Tiam1 mRNA expression levels in 49 cases of esophageal cancer tissues and normal esophageal tissues were detected. Results: Average Tiam1 mRNA expression level in 49 cases of esophageal cancer tissues (1.83 0.73) was significantly higher than that in normal esophageal tissues (0.87 0.45) (P < 0.01); High Tiam1 mRNA expression rate in esophageal cancer tissues was positively correlated with clinical stage and T stage; Tiam1 mRNA expression rate was 59.38% (19/32) in patients with lymph node metastasis, and in patients without lymph node metastasis it was 23.53% (4/17), with statistically significant differences (P < 0.05). Conclusion: Tiam1 gene expression in esophageal cancer tissues was significantly higher than that in normal esophageal tissues, and its overexpression was positively correlated with invasion and metastasis of esophageal cancer.

  5. Expression of epidermal growth factor receptor and CD44 splicing variants sharing exons 6 and 9 on gastric and esophageal carcinomas: a two-color flow-cytometric analysis.

    PubMed

    Koyama, S; Maruyama, T; Adachi, S

    1999-01-01

    Quantitative analysis based on the percentage of positive cells by two-color flow cytometry was used to quantify the surface expression of epidermal growth factor receptor (EGFR), and exons v6 and v9 of CD44 splice variants on tumor. Almost all patients with primary gastric and esophageal carcinomas, and benign mucosa of the stomach and esophagus showed usually high levels of EGFR expression, a mean of approximately 60% of cells being positive. Metastatic gastric carcinoma showed significantly higher levels of EGFR expression, a mean of 80% of cells being positive. Reduced expression of EGFR was observed in irradiated esophageal carcinoma. Adenocarcinomas, including primary and metastatic lesions, or cancer cell lines of the stomach revealed consistently very low or undetectable levels of expression of exon v6 of the CD44 variant (CD44v) protein. However, CD44v containing exon v9 could be detected in normal gastric epithelium and primary gastric carcinoma as well as in six adenocarcinoma cell lines. Exon v9 is significantly overexpressed on metastatic adenocarcinoma cells obtained from malignant ascites. On the other hand, normal squamous epithelium and primary squamous cell carcinoma (SCC) of the esophagus, and two SCC cell lines showed coexpression of exons v6 and v9 of CD44v. The expression of the CD44v6 molecule was significantly reduced in the irradiated primary SCC, although CD44v9 expression on the primary SCC remained unchanged after the radiation therapy. These results suggest that up-regulation of EGFR and CD44v9 molecules on gastric carcinomas, especially metastatic adenocarcinomas, shows tumor growth and tumor progression. In addition, down-regulation of EGFR and CD44v6 molecules on irradiated esophageal carcinoma may be involved in the mechanisms suppressing tumor growth and metastatic potential. PMID:10037277

  6. Upregulation of miRNA-143, -145, -192, and -194 in esophageal epithelial cells upon acidic bile salt stimulation.

    PubMed

    Bus, P; Siersema, P D; Verbeek, R E; van Baal, J W P M

    2014-08-01

    Barrett's esophagus (BE) is a metaplastic condition of the distal esophagus that occurs because of chronic gastroesophageal reflux. Previous studies have identified BE-specific microRNAs (miRNAs) in comparison with normal squamous epithelium (SQ). We hypothesized that BE-specific miRNAs could be induced in esophageal SQ cells by exposure to acid and/or bile salts. We aimed to determine whether BE-specific miRNAs are upregulated in an esophageal SQ cell line (Het-1A) in an environment with acid and/or bile salts and whether this is nuclear factor-?B (NF-?B) dependent. Acid and/or bile salt incubations were performed in Het-1A cells. Experiments were performed with or without inhibiting the NF-?B pathway. Quantitative reverse transcriptase polymerase chain reaction was performed to determine expression of miRNA-143, -145, -192, -194, cyclo-oxygenase-2 (COX2), mucin 2 (MUC2), and sex determining region Y-box 9. For validation, we determined levels of these miRNAs in biopsies from patients with reflux esophagitis and normal SQ. Significantly increased expression levels of miRNA-143 (2.7-fold), -145 (2.6-fold), -192 (2.0-fold), -194 (2.2-fold), COX2, MUC2, and sex determining region Y-box 9 were found upon acidic bile salt incubation, but not upon acid or bile salt alone. NF-?B pathway inhibition significantly decreased miRNA-143, -192, -194, COX2, and MUC2 expression. Additionally, miRNA-143, -145 and -194 expression was increased in reflux esophagitis biopsies compared with normal SQ, but no changes were found in miRNA-192 expression. Our findings suggest that upregulation of BE-specific miRNAs by acidic bile may be an early event in the transition of SQ to BE and that their expression is partly regulated by the NF-?B pathway. PMID:24006894

  7. Familial grouped pigmentation of the retinal pigment epithelium.

    PubMed Central

    de Jong, P T; Delleman, J W

    1988-01-01

    Grouped pigmentation of the retinal pigment epithelium was found in a father and his son. They had a normal resting potential on the electro-oculogram, but the son had a lower normal light rise. We believe this is the first description of familial grouped pigmentation. Images PMID:3390419

  8. Two cases of esophageal eosinophilia: eosinophilic esophagitis or gastro-esophageal reflux disease?

    PubMed

    Yilmaz, Ozlem; Karagol, Hacer Ilbilge Ertoy; Topal, Erdem; Unlusoy, Aysel Aksu; Egritas, Odul; Gonul, Ipek Isik; Bakirtas, Arzu

    2014-05-01

    Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease are among the major causes of isolated esophageal eosinophilia. Isolated esophageal eosinophilia meeting criteria for EoE may respond to proton pump inhibitor (PPI) treatment. This entity is termed proton pumps inhibitor responsive esophageal eosinophilia (PPI-REE). Gastro-esophageal reflux is thought to comprise a subgroup of patients with PPI-REE. According to the latest guidelines, PPI responsiveness distinguishes people with PPI-REE from patients having EoE (non-responders). In this report, two unusual cases with findings belonging to both EoE and PPI-REE are discussed with known and unknown facts. PMID:24987510

  9. Two Cases of Esophageal Eosinophilia: Eosinophilic Esophagitis or Gastro-Esophageal Reflux Disease?

    PubMed Central

    Yilmaz, Ozlem; Karagol, Hacer Ilbilge Ertoy; Topal, Erdem; Unlusoy, Aysel Aksu; Egritas, Odul; Gonul, Ipek Isik; Bakirtas, Arzu

    2014-01-01

    Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease are among the major causes of isolated esophageal eosinophilia. Isolated esophageal eosinophilia meeting criteria for EoE may respond to proton pump inhibitor (PPI) treatment. This entity is termed proton pumps inhibitor responsive esophageal eosinophilia (PPI-REE). Gastro-esophageal reflux is thought to comprise a subgroup of patients with PPI-REE. According to the latest guidelines, PPI responsiveness distinguishes people with PPI-REE from patients having EoE (non-responders). In this report, two unusual cases with findings belonging to both EoE and PPI-REE are discussed with known and unknown facts. PMID:24987510

  10. Reliability of balloon-mesh cytology in detecting esophageal carcinoma in a population of US veterans.

    PubMed

    Tsang, T K; Hidvegi, D; Horth, K; Ostrow, J D

    1987-02-01

    A catheter, equipped with a terminal balloon covered with nylon mesh, was developed to study the reliability of abrasive cytology for the diagnosis of esophageal carcinoma. Eighty-seven balloon cytology analyses were attempted in 82 subjects. Four patients were unable to swallow the balloon. In the 78 successful attempts, the initial diagnoses were: esophagitis (34) and esophageal carcinoma (13), established by endoscopic examination and histologic sampling; and normal esophagus (31) confirmed histologically in 25. The remaining 6 controls were younger than 40 years old, without any significant history of smoking, drinking and esophageal symptoms. For esophageal carcinoma, the sensitivity of balloon cytology was 91% and the specificity was 94% with four false-positives. Balloon cytology was generally well-tolerated and easily performed. This method is now being tested for screening high-risk patients for esophageal carcinoma. PMID:3791164

  11. Clinical experience of esophageal ulcers and esophagitis in AIDS patients.

    PubMed

    Yang, M T; Ko, F T; Cheng, N Y; Lin, K Y; Wang, C S; Siauw, C P; Shih, L S; Liao, S T

    1996-11-01

    In Taiwan, numbers of patients with the acquired immunodeficiency syndrome (AIDS) have been increasing in recent years. We present esophageal disease of different causes in 5(16%) heterosexual men among 31 AIDS patients over a 5-year period. Major symptoms included mild dysphagia in 4 (80%) patients and odynophagia in 3 (60%) patients. The duration of symptoms varied from 3 days to 6 months. The symptoms occurred before the diagnosis of AIDS in 3 patients. At esophagogastroduodenoscopy (endoscopy), all 5 patients had esophagitis and/or esophageal ulcers proved by histopathologic evaluation. Four had Candida esophagitis, 3 had cytomegalovirus esophagitis/ulcers and 2 had idiopathic esophageal ulcerations (IEU). Three patients had different esophagitis/ulcers at the same time or during follow-up. The median CD4 lymphocyte count at the time of diagnosis of esophageal disease was 12.2 cells/mm3 (range, 3 to 35 cells/mm3). The endoscopic pictures of the different causes of esophagitis/ ulcers lack uniformity in number, size and appearance. These observations make a conclusion that all AIDS patients with an esophageal disease should undergo endoscopy with biopsy to obtain a definitive diagnosis. PMID:8953856

  12. Virological diagnosis of herpes simplex virus 1 esophagitis by quantitative real-time PCR assay.

    PubMed

    Jazeron, Jean-François; Barbe, Coralie; Frobert, Emilie; Renois, Fanny; Talmud, Déborah; Brixi-Benmansour, Hedia; Brodard, Véronique; Andréoletti, Laurent; Diebold, Marie-Danièle; Lévêque, Nicolas

    2012-03-01

    Herpes simplex virus 1 (HSV-1) esophagitis diagnosis is routinely based on the endoscopic findings confirmed by histopathological examination of the esophagitis lesions. Virological diagnosis is not systematically performed and restricted to viral culture or to qualitative PCR assay from esophagitis biopsy specimens. The aim of this study was to assess the interest of quantitative real-time PCR assay in HSV-1 esophagitis diagnosis by comparing the results obtained to those of histological examination associated with immunohistochemical staining, which is considered the "gold standard." From 53 esophagitis biopsy specimens, the PCR assay detected HSV-1 in 18 of 19 histologically proven to have herpetic esophagitis and in 9 of 34 that had esophagitis related to other causes, demonstrating sensitivity, specificity, positive predictive value, and negative predictive value of 94.7%, 73%, 66.7%, and 96%, respectively. Interestingly, HSV-1 was not detected in 16 specimens without the histological aspect of esophagitis. The viral loads normalized per μg of total extracted DNA in each biopsy specimen detected positive by HSV PCR were then compared and appeared to be significantly higher in histopathologically positive herpetic esophagitis (median = 2.9 × 10(6) ± 1.1 × 10(8)) than in histopathologically negative herpetic esophagitis (median = 3.1 × 10(3) ± 6.2 × 10(3)) (P = 0.0009). Moreover, a receiver operating characteristics analysis revealed that a viral load threshold greater than 2.5 × 10(4) copies would allow an HSV-1 esophagitis diagnosis with a sensitivity and specificity of 83.3% and 100%, respectively. In conclusion, this work demonstrated that HSV quantitative PCR results for paraffin-embedded esophageal tissue was well correlated to histopathological findings for an HSV-1 esophagitis diagnosis and could be diagnostic through viral load assessment when histopathological results are missing or uncertain. PMID:22170921

  13. Esophageal diverticulum exposed during endoscopic submucosal dissection of superficial cancer

    PubMed Central

    Tanaka, Shinwa; Toyonaga, Takashi; Ohara, Yoshiko; Yoshizaki, Tetsuya; Kawara, Fumiaki; Ishida, Tsukasa; Hoshi, Namiko; Morita, Yoshinori; Azuma, Takeshi

    2015-01-01

    Endoscopic submucosal dissection (ESD) is now widely accepted as a strategy to treat superficial esophageal neoplasms. The rate of adverse events, such as perforation, has been decreasing with the improvement of devices and techniques. In this paper, we report a case of esophageal cancer that had a diverticulum under cancerous epithelium. The diverticulum was not detected during preoperative examination, and led to perforation during the ESD procedure. Our case shows that, although rare, some diverticula can exist underneath the mucosal surface without obvious depression. If there is any sign of hidden diverticula during ESD, surgeons should proceed with caution or, depending on the case, the procedure should be discontinued to avoid adverse events. PMID:25780314

  14. Viruses, Other Pathogenic Microorganisms and Esophageal Cancer

    PubMed Central

    Xu, Wenjia; Liu, Zhongshun; Bao, Qunchao; Qian, Zhikang

    2015-01-01

    Background Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. Summary Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. Key Message Among the above-mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. Practical Implications Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti-infection measures to prevent EC. PMID:26674173

  15. Epidemiology of esophageal cancer

    PubMed Central

    Zhang, Yuwei

    2013-01-01

    Esophageal cancer (EsC) is one of the least studied and deadliest cancers worldwide because of its extremely aggressive nature and poor survival rate. It ranks sixth among all cancers in mortality. In retrospective studies of EsC, smoking, hot tea drinking, red meat consumption, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barretts esophagus is clearly recognized as a risk factor for EsC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we investigated the epidemiologic patterns and causes of EsC. Using population based cancer data from the Surveillance, Epidemiology and End Results Program of the United States; we generated the most up-to-date stage distribution and 5-year relative survival by stage at diagnosis for 1998-2009. Special note should be given to the fact that esophageal cancer, mainly adenocarcinoma, is one of the very few cancers that is contributing to increasing death rates (20%) among males in the United States. To further explore the mechanism of development of EsC will hopefully decrease the incidence of EsC and improve outcomes. PMID:24039351

  16. Esophageal Preservation in Five Male Patients After Endoscopic Inner-Layer Circumferential Resection in the Setting of Superficial Cancer: A Regenerative Medicine Approach with a Biologic Scaffold

    PubMed Central

    Hoppo, Toshitaka; Nieponice, Alejandro; Gilbert, Thomas W.; Davison, Jon M.; Jobe, Blair A.

    2011-01-01

    As a result of injury caused by chronic gastroesophageal reflux, Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma are rapidly increasing problems in the United States. The current standard of care involves esophagectomy, a procedure associated with a high morbidity, a negative impact on long term quality of life, and a mortality rate of 16 percent. An entirely endoscopic technique for circumferential, long segment en bloc removal of the mucosa and submucosa with subsequent placement of a biologic scaffold material that promotes a constructive remodeling response and minimizes stricture is described herein. The results of this approach are reported for five patients with 424-month follow-up. Restoration of normal mature, K4+/K14+, squamous epithelium, and return to a normal diet without significant dysphagia is reported for all patients. Two of five patients show a small focus of recurrent Barrett's esophagus at the gastroesophageal junction, but the entire length and circumference of the reconstituted esophageal mucosa remains free of disease. This experience provides evidence that a regenerative medicine approach may, for the first time, enable aggressive endoscopic resection of early stage neoplasia without the need for esophagectomy and its associated complications. PMID:21306292

  17. 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

  18. Bacterial esophagitis associated with CD4+ T-lymphocytopenia without HIV infection. Possible role of corticosteroid treatment.

    PubMed

    Richert, S M; Orchard, J L

    1995-01-01

    Although infectious esophagitis is usually due to infection with Candida, herpes virus, or cytomegalovirus, bacterial esophagitis is occasionally observed. Recently, patients have been reported with CD4+ T-lymphocytopenia without HIV infection. Bacterial esophagitis per se has not been reported in these patients. We report the case of an 80-year-old patient admitted with a COPD exacerbation after being on chronic steroids. The patient developed esophageal symptoms and was found to have bacterial esophagitis by biopsy. Her CD4+ counts were found to be low, but she denied HIV risk factors and HIV testing was negative. Her CD4+ counts rose into the normal range as her steroids were tapered, and her esophagitis improved on antibiotics. This case is reported to alert physicians to the possible association of bacterial esophagitis with CD4+ T-lymphocytopenia without HIV infection and to discuss the possible etiological role of corticosteroid treatment. PMID:7821107

  19. Confocal fluorescence microendoscopy of bronchial epithelium.

    PubMed

    Lane, Pierre M; Lam, Stephen; McWilliams, Annette; Leriche, Jean C; Anderson, Marshall W; Macaulay, Calum E

    2009-01-01

    Confocal microendoscopy permits the acquisition of high-resolution real-time confocal images of bronchial mucosa via the instrument channel of an endoscope. We report here on the construction and validation of a confocal fluorescence microendoscope and its use to acquire images of bronchial epithelium in vivo. Our objective is to develop an imaging method that can distinguish preneoplastic lesions from normal epithelium to enable us to study the natural history of these lesions and the efficacy of chemopreventive agents without biopsy removal of the lesion that can introduce a spontaneous regression bias. The instrument employs a laser-scanning engine and bronchoscope-compatible confocal probe consisting of a fiber-optic image guide and a graded-index objective lens. We assessed the potential of topical application of physiological pH cresyl violet (CV) as a fluorescence contrast-enhancing agent for the visualization of tissue morphology. Images acquired ex vivo with the confocal microendoscope were first compared with a bench-top confocal fluorescence microscope and conventional histology. Confocal images from five sites topically stained with CV were then acquired in vivo from high-risk smokers and compared to hematoxylin and eosin stained sections of biopsies taken from the same site. Sufficient contrast in the confocal imagery was obtained to identify cells in the bronchial epithelium. However, further improvements in the miniature objective lens are required to provide sufficient axial resolution for accurate classification of preneoplastic lesions. PMID:19405738

  20. Confocal fluorescence microendoscopy of bronchial epithelium

    NASA Astrophysics Data System (ADS)

    Lane, Pierre M.; Lam, Stephen; McWilliams, Annette; Leriche, Jean C.; Anderson, Marshall W.; Macaulay, Calum E.

    2009-03-01

    Confocal microendoscopy permits the acquisition of high-resolution real-time confocal images of bronchial mucosa via the instrument channel of an endoscope. We report here on the construction and validation of a confocal fluorescence microendoscope and its use to acquire images of bronchial epithelium in vivo. Our objective is to develop an imaging method that can distinguish preneoplastic lesions from normal epithelium to enable us to study the natural history of these lesions and the efficacy of chemopreventive agents without biopsy removal of the lesion that can introduce a spontaneous regression bias. The instrument employs a laser-scanning engine and bronchoscope-compatible confocal probe consisting of a fiber-optic image guide and a graded-index objective lens. We assessed the potential of topical application of physiological pH cresyl violet (CV) as a fluorescence contrast-enhancing agent for the visualization of tissue morphology. Images acquired ex vivo with the confocal microendoscope were first compared with a bench-top confocal fluorescence microscope and conventional histology. Confocal images from five sites topically stained with CV were then acquired in vivo from high-risk smokers and compared to hematoxylin and eosin stained sections of biopsies taken from the same site. Sufficient contrast in the confocal imagery was obtained to identify cells in the bronchial epithelium. However, further improvements in the miniature objective lens are required to provide sufficient axial resolution for accurate classification of preneoplastic lesions.

  1. The pathogenesis of chronic eosinophilic esophagitis in SHARPIN-deficient mice.

    PubMed

    Chien, Syu-Jhe; Silva, Kathleen A; Kennedy, Victoria E; HogenEsch, Harm; Sundberg, John P

    2015-12-01

    Increased numbers of eosinophils in the esophagus are common in several esophageal and systemic diseases, and a prominent feature of eosinophilic esophagitis. Mouse models can provide insight into the mechanisms of eosinophil infiltration and their pathogenic role. SHARPIN-deficient cpdm mice develop a chronic proliferative dermatitis and an esophagitis characterized by epithelial hyperplasia and the accumulation of eosinophils in the serosa, submucosa, lamina propria and epithelium of the esophagus. We conducted a detailed investigation of the pathogenesis of the esophagitis by light microscopy, immunohistochemistry, and gene expression as the mice aged from 4 to 10weeks. The thickness of the esophageal epithelium and the number of eosinophils in the esophagus both increased with age. There were scattered apoptotic epithelial cells in mice at 6-10weeks of age that reacted with antibodies to activated caspase 3 and caspase 9. The expression of CCL11 (eotaxin-1), IL4, IL13 and TSLP was increased in cpdm mice compared with wild type (WT) mice, and there was no change in the expression of CCL24 (eotaxin-2), IL5 and IL33. The expression of chitinase-like 3 and 4 (YM1 and YM2) proteins, markers of type 2 inflammation, was greatly increased in cpdm mice, and this was replicated in vitro by incubation of WT esophagus in the presence of IL4 and IL13. Immunohistochemistry showed that these proteins were localized in esophageal epithelial cells. The severity of the esophagitis was not affected by crossing SHARPIN-deficient mice with lymphocyte-deficient Rag1 null mice indicating that the inflammation is independent of B and T lymphocytes. PMID:26321245

  2. Protective Effect of ECQ on Rat Reflux Esophagitis Model

    PubMed Central

    Jang, Hyeon-Soon; Han, Jeong Hoon; Jeong, Jun Yeong

    2012-01-01

    This study was designed to determine the protective effect of Rumex Aquaticus Herba extracts containing quercetin-3-?-D-glucuronopyranoside (ECQ) on experimental reflux esophagitis. Reflux esophagitis was induced by surgical procedure. The rats were divided into seven groups, namely normal group, control group, ECQ (1, 3, 10, 30 mg/kg) group and omeprazole (30 mg/kg) group. ECQ and omeprazole groups received intraduodenal administration. The Rats were starved for 24 hours before the experiments, but were freely allowed to drink water. ECQ group attenuated the gross esophagitis significantly compared to that treated with omeprazole in a dose-dependent manner. ECQ decreased the volume of gastric juice and increased the gastric pH, which are similar to those of omeprazole group. In addition, ECQ inhibited the acid output effectively in reflux esophagitis. Significantly increased amounts of malondialdehyde (MDA), myeloperoxidase (MPO) activity and the mucosal depletion of reduced glutathione (GSH) were observed in the reflux esophagitis. ECQ administration attenuated the decrement of the GSH levels and affected the MDA levels and MPO activity. These results suggest that the ECQ has a protective effect which may be attributed to its multiple effects including anti-secretory, anti-oxidative and anti-inflammatory actions on reflux esophagitis in rats. PMID:23269908

  3. 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

  4. Relationship between esophageal clinical symptoms and manometry findings in patients with esophageal motility disorders: a cross-sectional study

    PubMed Central

    FakhreYaseri, Hashem; FakhreYaseri, Ali Mohammad; Baradaran Moghaddam, Ali; Soltani Arabshhi, Seyed Kamran

    2015-01-01

    Background: Manometry is the gold-standard diagnostic test for motility disorders in the esophagus. The development of high-resolution manometry catheters and software displays of manometry recordings in color-coded pressure plots have changed the diagnostic assessment of esophageal disease. The diagnostic value of particular esophageal clinical symptoms among patients suspected of esophageal motor disorders (EMDs) is still unknown. The aim of this study was to explore the sensitivity, specificity, and predictive accuracy of presenting esophageal symptoms between abnormal and normal esophageal manometry findings. Methods: We conducted a cross-sectional study of 623 patients aged 11-80 years. Data were collected from clinical examinations as well as patient questionnaires. The sensitivity, specificity, and accuracy were calculated after high-resolution manometry plots were reviewed according to the most recent Chicago Criteria. Results: The clinical symptoms were not sensitive enough to discriminate between EMDs. Nevertheless, dysphagia, noncardiac chest pain, hoarseness, vomiting, and weight loss had high specificity and high accuracy to distinguish EMDs from normal findings. Regurgitation and heartburn did not have good accuracy for the diagnosis of EMDs. Conclusion: Clinical symptoms are not reliable enough to discriminate between EMDs. Clinical symptoms can, however, discriminate between normal findings and EMDs, especially achalasia. PMID:26793662

  5. UPPER ESOPHAGEAL SPHINCTER RESTING PRESSURE VARIES DURING ESOPHAGEAL MANOMETRY

    PubMed Central

    REZENDE, Daniel Tavares; HERBELLA, Fernando A. M.; SILVA, Luciana C.; PANOCCHIA-NETO, Sebastio; PATTI, Marco G.

    2014-01-01

    Background The upper esophageal sphincter is composed of striated muscle. The stress of intubation and the need to inhibit dry swallows during an esophageal manometry test may lead to variations in basal pressure of this sphincter. Upper esophageal sphincter is usually only studied at the final part of the test. Was observed during the performance of high resolution manometry that sphincter pressure may vary significantly over the course of the test. Aim To evaluate the variation of the resting pressure of the upper esophageal sphincter during high resolution manometry. Methods Was evaluated the variation of the basal pressure of the upper esophageal sphincter during high resolution manometry. Were reviewed the high resolution manometry tests of 36 healthy volunteers (mean age 31 years, 55% females). The basal pressure of the upper esophageal sphincter was measured at the beginning and at the end of a standard test. Results The mean time of the test was eight minutes. The basal pressure of the upper esophageal sphincter was 100 mmHg at the beginning of the test and 70 mmHg at the end (p<0.001). At the beginning, one patient had hypotonic upper esophageal sphincter and 14 hypertonic. At the end of the test, one patient had hypotonic upper esophageal sphincter (same patient as the beginning) and seven hypertonic upper esophageal sphincter. Conclusion A significant variation of the basal pressure of the upper esophageal sphincter was observed in the course of high resolution manometry. Probably, the value obtained at the end of the test may be more clinically relevant. PMID:25184767

  6. Loss of secondary esophageal peristalsis is not a contributory pathogenetic factor in posterior laryngitis.

    PubMed

    Ulualp, S O; Gu, C; Toohill, R J; Shaker, R

    2001-02-01

    Secondary esophageal peristalsis helps prevent the entry of gastric acid into the pharynx by clearing the refluxed gastric contents back into the stomach. Because the loss of this mechanism may contribute to the pathogenesis of reflux-induced laryngeal disorders, our aim was to study the frequency of stimulation and parameters of secondary esophageal peristalsis in patients with posterior laryngitis (PL). We studied 14 patients (45 +/- 5 years) with PL documented by videolaryngoscopy and 11 healthy controls (46 +/- 6 years). The upper esophageal sphincter (UES) pressure was monitored by a sleeve assembly incorporating an injection port 5 cm distal to the sleeve. The esophageal body and lower esophageal sphincter (LES) pressures were measured by an LES sleeve assembly. Primary esophageal peristalsis was induced by 5-mL water swallows. Secondary esophageal peristalsis was induced by abrupt injection of volumes of air, incrementally increased by 5 mL, into the esophagus. Secondary esophageal peristalsis could not be elicited by injection of any volume (up to 60 mL) in 3 PL patients and 2 controls. These 5 subjects had normal primary peristalsis. The threshold volume of air required to stimulate secondary esophageal peristalsis in PL patients (median, 15 mL) was similar to that of controls (median, 10 mL). The parameters of the secondary esophageal peristaltic pressure wave were similar in both groups, and in both groups, they were similar to those of primary peristalsis. The UES response to the injection of the threshold volume that induced secondary esophageal peristalsis in PL patients was contraction in 58% of the trials, partial relaxation in 3%, and no response in 39%. The findings were similar to those in the controls. The LES response to injection of the threshold volume was complete relaxation in both the PL patients and the controls. We conclude that the integrity of secondary esophageal peristalsis is preserved in PL patients. PMID:11219523

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

    PubMed

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

    2015-11-01

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

  8. Benign esophageal tumors.

    PubMed

    Ha, Cindy; Regan, James; Cetindag, Ibrahim Bulent; Ali, Aman; Mellinger, John D

    2015-06-01

    Benign esophageal and paraesophageal masses and cysts are a rare but important group of pathologies. Although often asymptomatic, these lesions can cause a variety of symptoms and, in some cases, demonstrate variable biological behavior. Contemporary categorization relies heavily on endoscopic ultrasound and other imaging modalities and immunohistochemical analysis when appropriate. Minimally invasive options including endoscopic, laparoscopic, and thoracoscopic methods are increasingly used for symptomatic or indeterminate lesions. PMID:25965126

  9. Activin A expression in esophageal carcinoma and its association with tumor aggressiveness and differentiation

    PubMed Central

    WANG, ZHENHUA; ZHANG, NING; SONG, RUIFENG; FAN, RUITAI; YANG, LIUQIN; WU, LIPING

    2015-01-01

    The aim of the present study was to investigate the expression of activin A in esophageal carcinoma and its association with tumor differentiation and metastasis. A total of 57 esophageal carcinoma patients and 36 controls were included in the current study. The mRNA and protein expression levels of activin A in esophageal tumors or normal esophageal tissues were determined by reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis. In addition, the association of activin A expression with esophageal carcinoma differentiation, metastasis and recurrence postoperatively was analyzed. The mRNA and protein expression levels of activin A in esophageal carcinoma were significantly higher compared with those in normal esophageal tissues (P<0.05). The expression of activin A was higher in poorly-/moderately-differentiated esophageal tumor tissues compared with that of well-differentiated or control tissues (P<0.05). Furthermore, the expression of activin A in poorly-differentiated esophageal tumor tissues was higher compared with that of moderately-differentiated tissues (P<0.05). A positive correlation was also observed between differentiation degree and activin A expression. The expression of activin A was higher in patients with lymph node metastasis compared with those without metastasis (P<0.05). The cumulative survival rate of patients with a high expression of activin A at 1, 2 and 3 years postoperatively was significantly decreased compared with that of patients with a lower expression of activin A (P<0.05); by contrast, the cumulative recurrence rate was significantly higher in patients with a lower activin A expression (P<0.05). In conclusion, abnormal expression of activin A was detected in esophageal tumor tissues, which was correlated with the tumor differentiation, metastasis, survival and recurrence. In conclusion, activin A may be used as an auxiliary index in the diagnosis and prognosis of clinical esophageal carcinoma. PMID:26170990

  10. Hypnotherapy for Esophageal Disorders

    PubMed Central

    Riehl, Megan E.; Keefer, Laurie

    2015-01-01

    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 symptomsvisceral 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

  11. Expression microarray analysis identifies novel epithelial-derived protein markers in eosinophilic esophagitis.

    PubMed

    Matoso, Andres; Mukkada, Vincent A; Lu, Shaolei; Monahan, Renee; Cleveland, Kelly; Noble, Lelia; Mangray, Shamlal; Resnick, Murray B

    2013-05-01

    Gene expression studies in eosinophilic esophagitis support an immune-mediated etiology associated with differential regulation of inflammatory and epithelial-derived genes. We aimed to further characterize epithelial gene expression alterations in eosinophilic esophagitis and to explore the use of immunohistochemistry to identify these alterations. Esophageal biopsies from pediatric patients with eosinophilic esophagitis before and after therapy with topical steroids (N=7) were screened by gene expression microarray and results were validated by RT-PCR. A larger group of eosinophilic esophagitis patients (N=42) was then used to evaluate protein expression by immunohistochemistry compared with reflux patients (N=15) and normal controls (N=17). Microarray and RT-PCR studies identified overexpression of ALOX15 and tumor necrosis factor alpha-induced factor 6 (TNFAIP6) and underexpression of filaggrin (FLG), SLURP1 and cysteine-rich secretory protein 3 (CRISP3) in eosinophilic esophagitis. Immunohistochemistry for ALOX15 was positive in 95% of eosinophilic esophagitis and negative in all controls, all eosinophilic esophagitis after therapy and all reflux biopsies (P<0.001). TNFAIP6 was positive in 88% of eosinophilic esophagitis samples versus 47% of controls, 29% of eosinophilic esophagitis after therapy and 40% of reflux samples (P=0.002). Overexpression of both ALOX15 and TNFAIP6 directly correlated with the degree of eosinophilic infiltration. FLG was positive in 88% of controls and 100% of reflux biopsies, but negative in all eosinophilic esophagitis samples, and its expression was regained in 86% of eosinophilic esophagitis after therapy patients (P<0.001). SLURP1 expression was positive in all controls and reflux samples, but only positive in 5% of eosinophilic esophagitis and was re-expressed to 100% positivity in eosinophilic esophagitis after therapy patients (P<0.001). The majority of controls (89%) and reflux biopsies (100%) were positive for CRISP3 while eosinophilic esophagitis before therapy were positive in 14% of samples (P<0.001) with partial recovery after treatment (43%, P=0.105). This study identified five epithelial-derived markers differentially expressed in eosinophilic esophagitis easily detectable by immunohistochemistry with potential diagnostic utility. PMID:23503644

  12. Widespread Hypomethylation Occurs Early and Synergizes with Gene Amplification during Esophageal Carcinogenesis

    PubMed Central

    Alvarez, Hector; Sohal, Davendra; Fazzari, Melissa J.; Yu, Yiting; Montagna, Christina; Montgomery, Elizabeth A.; Canto, Marcia; Dunbar, Kerry B.; Wang, Jean; Roa, Juan Carlos; Mo, Yongkai; Bhagat, Tushar; Ramesh, K. H.; Cannizzaro, Linda; Mollenhauer, J.; Thompson, Reid F.; Suzuki, Masako; Meltzer, Stephen; Melnick, Ari; Greally, John M.; Maitra, Anirban; Verma, Amit

    2011-01-01

    Although a combination of genomic and epigenetic alterations are implicated in the multistep transformation of normal squamous esophageal epithelium to Barrett esophagus, dysplasia, and adenocarcinoma, the combinatorial effect of these changes is unknown. By integrating genome-wide DNA methylation, copy number, and transcriptomic datasets obtained from endoscopic biopsies of neoplastic progression within the same individual, we are uniquely able to define the molecular events associated progression of Barrett esophagus. We find that the previously reported global hypomethylation phenomenon in cancer has its origins at the earliest stages of epithelial carcinogenesis. Promoter hypomethylation synergizes with gene amplification and leads to significant upregulation of a chr4q21 chemokine cluster and other transcripts during Barrett neoplasia. In contrast, gene-specific hypermethylation is observed at a restricted number of loci and, in combination with hemi-allelic deletions, leads to downregulatation of selected transcripts during multistep progression. We also observe that epigenetic regulation during epithelial carcinogenesis is not restricted to traditionally defined “CpG islands,” but may also occur through a mechanism of differential methylation outside of these regions. Finally, validation of novel upregulated targets (CXCL1 and 3, GATA6, and DMBT1) in a larger independent panel of samples confirms the utility of integrative analysis in cancer biomarker discovery. PMID:21483804

  13. Adenocarcinoma of retinal pigment epithelium.

    PubMed Central

    Ramahefasolo, S; Soubrane, G; Dhermy, P; Godel, V; Regenbogen, L; Coscas, G

    1987-01-01

    This report describes a 41-year-old man with an intraocular tumour misinterpreted clinically as choroidal melanoma. The fluorescein angiographic features were not fully characteristic of uveal malignancy, and indeed histopathology revealed the diagnosis of adenocarcinoma of the retinal pigment epithelium. It is suggested that, in cases with the fundus and angiographic findings described here, the rare possibility of adenocarcinoma of retinal pigment epithelium should be kept in mind. Of particular interest were the changing pathological findings in the various parts of the tumour, which paralleled the fluorescein angiographic pattern. Images PMID:3651364

  14. Cytoprotective effects of hydrogen sulfide in novel rat models of non-erosive esophagitis.

    PubMed

    Zayachkivska, Oksana; Havryluk, Olena; Hrycevych, Nazar; Bula, Nazar; Grushka, Oksana; Wallace, John L

    2014-01-01

    Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barrett's esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively). Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury. PMID:25333941

  15. Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis

    PubMed Central

    Zayachkivska, Oksana; Havryluk, Olena; Hrycevych, Nazar; Bula, Nazar; Grushka, Oksana; Wallace, John L.

    2014-01-01

    Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barretts esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively). Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury. PMID:25333941

  16. 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.

  17. Manometric features of Eosinophilic Esophagitis in Esophageal Pressure Topography

    PubMed Central

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

    2010-01-01

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

  18. Free radicals and antioxidant systems in reflux esophagitis and Barretts esophagus

    PubMed Central

    Jimnez, Pilar; Piazuelo, Elena; Snchez, M. Teresa; Ortego, Javier; Soteras, Fernando; Lanas, Angel

    2005-01-01

    AIM: Experimental studies suggest that free radicals are involved in acid and pepsin-induced damage of esophageal mucosa. The profile and balance between free radicals and antioxidant systems in human esophagitis are unknown. METHODS: Superoxide anion and its powerful oxidant reaction with nitric oxide (peroxynitrite) generation were determined in esophageal mucosal biopsies from 101 patients with different gastro-esophageal reflux diseases and 28 controls. Activity of both superoxide dismutase (SOD) and catalase, and reduced glutathione (GSH) levels, were also assessed. Expression of Cu,ZnSOD, MnSOD and tyrosine-nitrated MnSOD were analyzed by Western blot and/or immunohistochemistry. RESULTS: The highest levels of superoxide anion generation were found in patients with severe lesions of esophagitis. Peroxynitrite generation was intense in Barretts biopsies, weaker in esophagitis and absent/weak in normal mucosa. Expression of Cu,ZnSOD and MnSOD isoforms were present in normal mucosa and increased according to the severity of the lesion, reaching the highest level in Barretts esophagus. However, SOD mucosal activity significantly decreased in patients with esophagitis and Barretts esophagus, which was, at least in part, due to nitration of its tyrosine residues. Catalase activity and GSH levels were significantly increased in mucosal specimens from patients with esophagitis and/or Barretts esophagus. CONCLUSION: A decrease in SOD antioxidant activity leading to increased mucosal levels of superoxide anion and peroxynitrite radicals may contribute to the development of esophageal damage and Barretts esophagus in patients with gastroesophageal reflux. Administration of SOD may be a therapeutic target in the treatment of patients with esophagitis and Barretts esophagus. PMID:15884106

  19. Feasibility of Imaging Esophageal Cancer with Labeled Somatostatin Analogue

    PubMed Central

    Herlin, Gunnar; Idestrm, Lars; Lundell, Lars; Aspelin, Peter; Axelsson, Rimma

    2011-01-01

    Background. While the surface of a cell normally has some amount of somatostatin receptors, these receptors are overexpressed to a very high degree in multiple neoplastic diseases. No data exist for esophageal carcinoma. Purpose. To find out whether esophageal carcinoma could be imaged using somatostatin receptor scintigraphy. Material and Methods. 34 patients with esophageal lesions were prospectively examined by 99mTc-depreotide scintigraphy 2 and 4 hours after injection. Quantitative evaluation of 99mTc-depreotide uptake was performed around the lesion (T) and in healthy lung parenchyma (B). The relative uptake was calculated as T?B/B. Scintigraphy results were compared with histopathology from surgery or biopsy specimens from endoscopic ultrasonography. Results. 21 patients had esophageal cancer, and 13 lesions were benign. Visual assessment revealed positive 99mTc-depreotide uptake in 16 of the 21 cancers. The 13 patients without cancer had no depreotide uptake. The Mann-Whitney U test showed a statistically significant difference (P < .005) between 99mTc-depreotide uptake in malignant and benign lesions, for both the 2-hour and the 4-hour measurements. Conclusion. Scintigraphic examination with 99mTc-depreotide is feasible for imaging esophageal cancer, but the method is not suitable neither for screening or primary diagnosis, because of methods modest sensitivity. Our first results showed high specificity which should be used with caution, as the number of patients was relatively low. Further studies are needed to determine the role of the method. PMID:21716646

  20. Esophageal impacted dentures.

    PubMed Central

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

    2004-01-01

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

  1. 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.

  2. Epigenetic regulation of the intestinal epithelium.

    PubMed

    Elliott, Ellen N; Kaestner, Klaus H

    2015-11-01

    The intestinal epithelium is an ideal model system for the study of normal and pathological differentiation processes. The mammalian intestinal epithelium is a single cell layer comprising proliferative crypts and differentiated villi. The crypts contain both proliferating and quiescent stem cell populations that self-renew and produce all the differentiated cell types, which are replaced every 3-5days. The genetics of intestinal development, homeostasis, and disease are well defined, but less is known about the contribution of epigenetics in modulating these processes. Epigenetics refers to heritable phenotypic traits, including gene expression, which are independent of mutations in the DNA sequence. We have known for several decades that human colorectal cancers contain hypomethylated DNA, but the causes and consequences of this phenomenon are not fully understood. In contrast, tumor suppressor gene promoters are often hypermethylated in colorectal cancer, resulting in decreased expression of the associated gene. In this review, we describe the role that epigenetics plays in intestinal homeostasis and disease, with an emphasis on results from mouse models. We highlight the importance of producing and analyzing next-generation sequencing data detailing the epigenome from intestinal stem cell to differentiated intestinal villus cell. PMID:26220502

  3. Experimental reconstruction of cervical esophageal defect with artificial esophagus made of polyurethane in a dog model.

    PubMed

    Jiang, H; Cui, Y; Ma, K; Gong, M; Chang, D; Wang, T

    2016-01-01

    The defect of esophagus after surgical excision in patients is usually replaced by autologous stomach, jejunum, or colon. The operation brings severe trauma and complications. Using artificial esophagus to replace the defect in situ can reduce the operative trauma, simplify the operative procedures, and decrease the influence to digestive function. A variety of experiments have been designed for developing a practical artificial esophagus. Nevertheless, a safe and reliable artificial esophagus is not yet available. The objective is to evaluate the possibility of the artificial esophagus made of non-degradable polyurethane materials being used in reconstruction of the segmental defect of cervical esophagus in beagles, observe the regeneration of esophageal tissue, and gather experience for future study. The cervical esophageal defects in 13 beagles were designed to 2-cm long and were constructed by the artificial esophagus made of non-degradable polyurethane materials. Nutrition supports were given after the operation. The operative mortality, anastomotic leakage, migration of artificial esophagus, and dysphagia were followed up. The regeneration of the esophageal tissues was evaluated by histopathology and immunohistochemical labeled streptavidin-biotin method. The surgical procedures were successfully completed in all beagles, and 12-month follow-ups were done. Only one beagle died of severe infection, and all others survived until being killed. The anastomotic leakage occurred in nine beagles, most of them (8/9) were cured after supportive therapy. The migration of artificial esophagus occurred in all 12 surviving beagles, and one artificial esophagus stayed in situ after migration. All 12 surviving beagles showed dysphagia with taking only fluid or soft food. No beagle died of malnutrition. The neo-esophagus was composed of granulation tissue, and the inner surface was covered by epithelium in 2-3 months completely. But the inner surface of neo-esophagus with artificial esophagus staying in situ after migration was not covered by epithelium, and the granulation tissue was infiltrated by a great deal of inflammatory cells. Antibodies against cytokeratin were positively expressed in epithelium of neo-esophagus. Up to 12 months after operation, antibodies against smooth muscle actin and desmin were both negatively expressed in neo-esophagus. The artificial esophagus made of non-degradable polyurethane reconstructing cervical esophageal defect is practicable. Although there are some problems, including anastomotic leakage, migration, and dysphagia, they are not lethal following good supportive therapy. The esophageal epithelium can regenerate with the supporting role of artificial esophagus. In the future, deformable artificial esophagus should be improved, and a much longer follow-up will be performed to evaluate whether the esophageal gland and skeletal muscle can regenerate. PMID:25074403

  4. Gene expression profiles at different stages of human esophageal squamous cell carcinoma

    PubMed Central

    Zhou, Jin; Zhao, Li-Qun; Xiong, Mo-Miao; Wang, Xiu-Qin; Yang, Guan-Rui; Qiu, Zong-Liang; Wu, Min; Liu, Zhi-Hua

    2003-01-01

    AIM: To characterize the gene expression profiles in different stages of carcinogenesis of esophageal epithelium. METHODS: A microarray containing 588 cancer related genes was employed to study the gene expression profile at different stages of esophageal squamous cell carcinoma including basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer. Principle component analysis was performed to search the genes which were important in carcinogenesis. RESULTS: More than 100 genes were up or down regulated in esophageal epithelial cells during the stages of basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer. Principle component analysis identified a set of genes which may play important roles in the tumor development. Comparison of expression profiles between these stages showed that some genes, such as P160ROCK, JNK2, were activated and may play an important role in early stages of carcinogenesis. CONCLUSION: These findings provided an esophageal cancer-specific and stage-specific expression profiles, showing that complex alterations of gene expression underlie the development of malignant phenotype of esophageal cancer cells. PMID:12508342

  5. 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.

  6. [Esophageal involvement in Behet's disease].

    PubMed

    Martnez Salmern, J F; Gutirrez-Rave Pecero, V; Uariachi, M; Ogea Garca, J L; Franco Cebrin, J; Castillo Higueras, P

    1992-09-01

    We report the case of a female patient that fulfills major criteria of Behcet's disease. Multiple esophageal aphthous ulcers seen by endoscopy responded to therapy with steroids and colchicine. PMID:1419316

  7. 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 mat, 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

  8. Eosinophilic Esophagitis and Gastroenteritis.

    PubMed

    Cianferoni, Antonella; Spergel, Jonathan M

    2015-09-01

    Eosinophilic gastrointestinal disease (EGID) can be classified as eosinophilic esophagitis (EoE) when the eosinophilia is limited to the esophagus or as eosinophilic gastritis (EG) if it is limited to the gastric tract, eosinophilic colitis (EC) if it is limited to the colon, and eosinophilic gastroenteritis (EGE) if the eosinophilia involves one or more parts of the gastrointestinal tract. EoE is by far the most common EGID. It is a well-defined chronic atopic disease due to a T helper type 2 (Th2) inflammation triggered often by food allergens. EoE diagnosis is done if an esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf). Globally accepted long-term therapies for EoE are the use of swallowed inhaled steroids or food antigen avoidance. The treatment of EoE is done not only to control symptoms but also to prevent complications such as esophageal stricture and food impaction. EGE cause non-specific gastrointestinal (GI) symptoms and are diagnosed if esophagogastroduodenoscopy (EGD)/colonoscopy show eosinophilia in one or more parts of the GI tract. They are rare diseases with an unclear pathogenesis, and they are poorly defined in terms of diagnostic criteria and treatment. Before initiating treatment of any EGE, it is imperative to conduct a differential diagnosis to exclude other causes of hypereosinophilia with GI localization. EGE are often poorly responsive to therapy and there is no commonly accepted long-term treatment. EG has many characteristics similar to EoE, including the fact that it is often due to a food allergen-driven Th2 inflammation; transcriptome analysis however shows that it is more a systemic disease and has a different gene signature than EoE. EC is a benign form of delayed food allergy in infant and is instead a difficult-to-treat severe inflammatory condition in older children and adults. EC in the latter groups can be a manifestation of drug allergy or autoimmune disease. Overall EGE, EC, and EG are rare and are a diagnosis of exclusion until more common causes of eosinophilia have been excluded. PMID:26233430

  9. Upper esophageal and pharyngeal cancers

    PubMed Central

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

    2014-01-01

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

  10. Human Retinal Pigment Epithelium Stem Cell (RPESC).

    PubMed

    Saini, Janmeet S; Temple, Sally; Stern, Jeffrey H

    2016-01-01

    The retinal pigment epithelium (RPE) is a pigmented cellular monolayer that supports photoreceptor cells located in the overlying neural retina. The RPE is critical for vision and its dysfunction results in numerous pathologies, several with limited available disease-altering strategies. Regeneration of the retina from RPE is robust in lower vertebrates, but is not normally exhibited in mammals. We recently found that a subpopulation of human RPE cells can be stimulated in culture to generate multipotent self-renewing cells-the RPE stem cell (RPESC). RPESC can be expanded to generate RPE progeny that are a potential source for cell replacement therapy. Alternatively, RPESC can produce mesenchymal progeny which serve as a disease model of epiretinal membrane formation. Yet another potential application of RPESCs is activation within the eye to awaken dormant endogenous repair. PMID:26427459

  11. 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

  12. Cutaneous metastases from esophageal adenocarcinoma.

    PubMed

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

    2015-03-01

    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

  13. Esophageal space-occupying lesion caused by Ascaris lumbricoides

    PubMed Central

    Zheng, Ping-Ping; Wang, Bing-Yuan; Wang, Fei; Ao, Ran; Wang, Ying

    2012-01-01

    Ascaris lumbricoides is the largest intestinal nematode parasite of man, which can lead to various complications because of its mobility. As the esophagus is not normal habitat of Ascaris, the report of esophageal ascariasis is rare. An old female presented with dysphagia after an intake of several red bean buns and haw jellies. The barium meal examination revealed a spherical defect in the lower esophagus. Esophageal bezoar or esophageal carcinoma was considered at the beginning. The patient fasted, and received fluid replacement treatment as well as some oral drugs such as proton pump inhibitor and sodium bicarbonate. Then upper gastrointestinal endoscopy was done to further confirm the diagnosis and found a live Ascaris lumbricoides in the gastric antrum and two in the duodenal bulb. The conclusive diagnosis was ascariasis. The esophageal space-occupying lesion might be the entangled worm bolus. Anthelmitnic treatment with mebendazole improved patients clinical manifestations along with normalization of the radiological findings during a 2-wk follow-up. Authors report herein this rare case of Ascaris lumbricoides in the esophagus, emphasizing the importance of awareness of this parasitic infection as it often presents with different and unspecific symptoms. PMID:22509089

  14. Prospective assessment of the diagnostic utility of esophageal brushings in adults with eosinophilic esophagitis.

    PubMed

    Kern, E; Lin, D; Larson, A; Yang, G-Y; Taft, T; Zalewski, A; Gonsalves, N; Hirano, I

    2016-01-01

    Patients with eosinophilic esophagitis (EoE) undergo multiple endoscopies with biopsy for both diagnosis and assessment of treatment response, which is inconvenient and costly. Brush cytology has been examined in Barrett's esophagus to reduce the need for repeated endoscopic biopsies. The aim of this pilot study was to evaluate the ability of brush cytology to detect mucosal eosinophilia in patients with EoE. This prospective study included adults with untreated and treated esophageal eosinophilia undergoing endoscopy at a tertiary care center. Patients received paired brushings and biopsies at the proximal and distal esophagus. A blinded pathologist quantified the number of eosinophils and epithelial cells per high-power field (hpf) on the cytology slides. The ratio of eosinophils/epithelial cells was used to normalize the cytology specimens for density of cells collected. The main outcome measures were sensitivity and specificity of brush cytology, and correlation between cytology and histology. Twenty-eight patients enrolled. The average age of the cohort was 37.7 ± 10.4 years; 75% of subjects were male. The sensitivity of cytology was 67-69% at the proximal esophagus and 70-72% at the distal esophagus. The specificity was 61-67% proximally and 70-75% distally. Histology was not significantly correlated with the max ratio of eosinophils/epithelial cells per hpf or the absolute number of eosinophils on cytology slides. Cytology using esophageal brushing has limited sensitivity and specificity for the detection of esophageal mucosal eosinophilia. The presence of exudates on endoscopy increased the detection of eosinophilia, which could make cytology useful in pediatric EoE, which often has a more exudative presentation. Diagnostic yield may improve with alternative acquisition techniques or the incorporation of eosinophil degranulation proteins. PMID:25515533

  15. Reduced 15S-Lipoxygenase-2 Expression in Esophageal Cancer Specimens and Cells and Upregulation In Vitro by the Cyclooxygenase-2 Inhibitor, NS3981

    PubMed Central

    Xu, Xiao-Chun; Shappell, Scott B; Liang, Zhengdong; Song, Shumei; Menter, David; Subbarayan, Vemparala; Iyengar, Sunita; Tang, Dean G; Lippman, Scott M

    2003-01-01

    Abstract Alterations in arachidonic acid metabolism are involved in human carcinogenesis. Cyclooxygenase (COX) and lipoxygenase (LOX) are key enzymes in this metabolism. We analyzed the expression of 15S-lipoxygenase-2 (15-LOX-2) mRNA and protein in surgical specimens from normal (N=37) and malignant (63) esophageal tissues using in situ hybridization and immunohistochemistry (IHC), and in normal (1), premalignant (1), and malignant (5) esophageal cell lines using Northern and Western blotting. 15-LOX-2 was expressed in normal esophageal epithelial cells (EECs) at the highest levels, whereas an SV40-immortalized HET-1A line and three of five esophageal cancer cell lines failed to express it at detectable levels. 15-LOX-2 was detected in 76% (28/37) of the normal esophageal mucosae, but only in 46% (29/63) of the cancer specimens using IHC (P<.01). Transient transfection of 15-LOX-2 expression vectors into esophageal cancer cells significantly inhibited the proliferation of 15-LOX-2-negative cancer cells. The COX-2 inhibitor, NS398, induced 15-LOX-2 expression in esophageal cancer cells, which is associated with reduced cell viability. This study demonstrated that 15-LOX-2 expression is lost in esophageal cancers and that the induction of 15-LOX-2 can inhibit cancer cell proliferation. Further investigation of the effects of nonsteroidal anti-inflammatory drugs on 15-LOX-2 expression and apoptosis in esophageal cancer cells may be warranted. PMID:12659684

  16. 1H-NMR based metabonomic profiling of human esophageal cancer tissue

    PubMed Central

    2013-01-01

    Background The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research. Methods In the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n = 89) and normal esophageal mucosae (n = 26) using a 1H nuclear magnetic resonance (1H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant anlaysis (OPLS-DA) were applied to analyse 1H-NMR profiling data to identify potential biomarkers. Results The constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of esophageal cancer tissues, indicating the attribution of metabolites disturbance to the progression of esophageal cancer. The potential biomarkers provide a promising molecular diagnostic approach for clinical diagnosis of human esophageal cancer and a new direction for the mechanism study. PMID:23556477

  17. Radionuclide esophageal transit of a liquid bolus: A reappraisal

    SciTech Connect

    Holloway, R.H.; Lange, R.C.; Magyar, L.; Greene, R.; McCallum, R.W.

    1984-01-01

    Measurement of radionuclide esophageal transit (RT) using a liquid bolus has been suggested as a screening test for esophageal motor disorders (EMD). The authors prospectively evaluated RT in 49 patients referred for esophageal manometry. Ten subjects with normal manometry served as controls. RT was performed using two 10 ml boluses of water labeled with 250 ..mu..Ci /sup 99m/Tc-sulfur colloid. Patients were studied supine and the swallow sequences framed in 1 second intervals. Transit time was measured from the time of entry to the time of exit from the esophagus. Mean transit time in normal subjects was 9.1 +- 2.1 (SD) sec. The test was abnormal if the transit time was prolonged (> 15 sec) in at least 1 of 2 swallows. RT agreed with manometry in 36/49 patients (75%), including 9/9 achalasics, 3/3 diffuse esophageal spasm, 3/7 'nutcracker esophagus' and 7/8 non-specific motor disorders (NSMD). 4/18 patients with normal manometry had abnormal RT. 9/31 patients with abnormal manometry had normal RT, including 4/7 nutcracker esophagus, 3/3 hypertrensive LES, 1/1 scleroderma and 1/8 NSMD. Sensitivity of RT was 70% and specificity 77%. The false positive rate was 15% and the false negative rate 39%. The authors conclude the following: 1) RT identifies patients with absent or impaired peristalsis; 2) There is substantial incidence of false negatives among patients with manometric disorders but normal peristalsis; and 3) Abnormal RT did occur in some patients with normal menometry. RT using a liquid bolus may not be sensitive enough as a screening test for EMD, but it may be an important adjunct to manometry.

  18. Epithelium

    MedlinePLUS

    ... secretions. Certain types of epithelial cells have tiny hairs called cilia, which help remove foreign substances. Epithelial cells are arranged in single, or multiple layers, depending on the organ and location.

  19. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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, Barretts 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 significantly in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only. The mRNA levels of cyclin D1 (5.8 1.9 vs 3.4 1.3, P < 0.01), c-Myc (6.4 1.7 vs 3.7 1.2, P < 0.01), and Bax (8.6 1.6 vs 5.1 1.3, P < 0.01) were significantly increased, whereas the mRNA level of Bcl-2 (0.6 0.3 vs 0.8 0.3, P < 0.01) was significantly reduced in rats with EGDA and concomitant esophageal H. pylori colonization compared with rats with EGDA only. CONCLUSION: Esophageal H. pylori colonization increases esophagitis severity, and facilitates the development of BE and EAC with the augmentation of cell proliferation and apoptosis in esophageal mucosa. PMID:25400455

  5. Glucose metabolism in rat retinal pigment epithelium.

    PubMed

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress. PMID:16475003

  6. Esophageal perforation during or after conformal radiotherapy for esophageal carcinoma

    PubMed Central

    Chen, Hai-yan; Ma, Xiu-mei; Ye, Ming; Hou, Yan-li; Xie, Hua-Ying; Bai, Yong-rui

    2014-01-01

    The aim of this study was to analyze the risk factors and prognosis for patients with esophageal perforation occurring during or after radiotherapy for esophageal carcinoma. We retrospectively analyzed 322 patients with esophageal carcinoma. These patients received radiotherapy for unresectable esophageal tumors, residual tumors after operation, or local recurrence. Of these, 12 had radiotherapy to the esophagus before being admitted, 68 patients had concurrent chemoradiotherapy (CRT), and 18 patients had esophageal perforation after RT (5.8%). Covered self-expandable metallic stents were placed in 11 patients. Two patients continued RT after stenting and control of infection; one of these suffered a new perforation, and the other had a massive hemorrhage. The median overall survival was 2 months (03 months) compared with 17 months in the non-perforation group. In univariate analysis, the Karnofsky performance status (KPS) being ?70, age younger than 60, T4 stage, a second course of radiotherapy to the esophagus, extracapsular lymph nodes (LN) involving the esophagus, a total dose >100 Gy (biologically effective dose?10), and CRT were risk factors for perforation. In multivariate analysis, age younger than 60, extracapsular LN involving the esophagus, T4 stage, and a second course of radiotherapy to the esophagus were risk factors. In conclusion, patients with T4 stage, extracapsular LN involving the esophagus, and those receiving a second course of RT should be given particular care to avoid perforation. The prognosis after perforation was poor. PMID:24914102

  7. Prevention and treatment of esophageal stenosis after endoscopic submucosal dissection for early esophageal cancer.

    PubMed

    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

  8. 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

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

    PubMed Central

    Liu, Dabiao

    2015-01-01

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

  10. 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. (a) Identification. An esophageal stethoscope is...

  11. Microperoxisomes in retinal pigment epithelium.

    PubMed

    Robison, W G; Kuwabara, T

    1975-11-01

    Microperoxisomes were found to be abundant in the retinal pigment epithelium of the human, rhesus monkey, mice, rats, domestic fowl, and frog by ultrastructural histochemistry. They were rare in other cells of the retina and choroid. These organelles had a granular matrix, ranged in diameter from 0.15 mum to 0.30 mum, and were bound by a single tripartite membrane which often maintained slender connections with the smooth endoplasmic reticulum and other microperoxisomes. They exhibited a positive reaction (electron opaque product) following incubation in diaminobenzidine and H2O2 for the demonstration of the peroxidatic activity of catalase (Novikoff et al., J. Histochem. Cytochem. 20: 1006, 1972). The reaction was inhibited by: (1) aminotriazole; (2) dichlorophenol-indophenol; (3) preheating at 95 degrees C.; or (4) elimination of H2O2. Microperoxisomes, like the well-known peroxisomes (microbodies) of liver cells have been inplicated in various aspects of lipid metabolism and the detoxification of H2O2. We demonstrated for the first time that microperoxisomes respond to drug-induced changes in lipid metabolism, as previously shown for peroxisomes. Nafenopin is a recently utilized drug which greatly decreases serum lipids, increases hepatic catalase activity, and induces an increased size and number of hepatic peroxisomes. Black, beige, albino, and obese mutant mice of the C57BL/6J strain treated with nafenopin for several weeks showed a two- to threefold increase in the number of microperoxisomes in the retinal pigment epithelium. Microperoxisomes of the retinal pigment epithelium may be involved in the transport, storage, and rapid turnover of lipids associated with the maintenance of photoreceptor outer segment disc membranes. PMID:810456

  12. Esophageal fistula associated with intracavitary irradiation for esophageal carcinoma

    SciTech Connect

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

    1986-05-01

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

  13. Interactions of oxygen radicals with airway epithelium.

    PubMed Central

    Wright, D T; Cohn, L A; Li, H; Fischer, B; Li, C M; Adler, K B

    1994-01-01

    Reactive oxygen species (ROS) have been implicated in the pathogenesis of numerous disease processes. Epithelial cells lining the respiratory airways are uniquely vulnerable regarding potential for oxidative damage due to their potential for exposure to both endogenous (e.g., mitochondrial respiration, phagocytic respiratory burst, cellular oxidases) and exogenous (e.g., air pollutants, xenobiotics, catalase negative organisms) oxidants. Airway epithelial cells use several nonenzymatic and enzymatic antioxidant mechanisms to protect against oxidative insult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, catalase, and glutatione peroxidase are major sources of antioxidant protection. Other materials associated with airway epithelium such as mucus, epithelial lining fluid, and even the basement membrane/extracellular matrix may have protective actions as well. When the normal balance between oxidants and antioxidants is upset, oxidant stress ensues and subsequent epithelial cell alterations or damage may be a critical component in the pathogenesis of several respiratory diseases. Oxidant stress may profoundly alter lung physiology including pulmonary function (e.g., forced expiratory volumes, flow rates, and maximal inspiratory capacity), mucociliary activity, and airway reactivity. ROS may induce airway inflammation; the inflammatory process may serve as an additional source of ROS in airways and provoke the pathophysiologic responses described. On a more fundamental level, cellular mechanisms in the pathogenesis of ROS may involve activation of intracellular signaling enzymes including phospholipases and protein kinases stimulating the release of inflammatory lipids and cytokines. Respiratory epithelium may be intimately involved in defense against, and pathophysiologic changes invoked by, ROS. PMID:7705313

  14. Squamous Tissue Lymphocytes in the Esophagus of Controls and Patients with Reflux Esophagitis and Barrett’s Esophagus Are Characterized by a Non-Inflammatory Phenotype

    PubMed Central

    Lind, Alexandra; Koenderman, Leo; Kusters, Johannes G.; Siersema, Peter D.

    2014-01-01

    Background and Objective Reflux esophagitis (RE) is characterized by inflammation of the squamous epithelium (SQ) of the esophagus and may progress to Barrett’s esophagus (BE) characterized by intestinal metaplasia. The role of inflammation in this transition has been postulated but lacks experimental evidence. Here, the inflammatory responses in the esophagus of these patients were investigated. Patients and Methods Fifty-one esophageal biopsies from with patients BE (n = 19), RE (n = 8) and controls (n = 23) were analyzed. T-cells were analyzed before and after ex vivo expansion (14 days) by multicolor flow cytometric analysis. The following markers were studied: CD3, CD4, CD8 (T-cell markers), Granzyme B (marker of cytotoxicity), CD103 (αE/epithelial integrin) and NKg2a (inhibitory receptor on T-cells and NK-cells). Results Analysis of ex vivo cultures from normal looking SQ from controls, RE patients, and BE patients revealed no significant differences in the number and phenotypes of T-cells. In contrast, tissue from RE was different to normal SQ in four aspects: 1) higher percentages of CD3+CD4+-cells (72±7% vs 48±6%, p = 0.01) and 2) CD8+GranzymeB+ -cells (53±11% vs 26±4%, p<0.05), while 3) lower percentages of CD4+CD103+-cells (45±19% vs 80±3%, p = 0.02) and 4) CD8+NKg2a+- cells (31±12% vs 44±5%). Conclusion Despite the fact that both tissues are exposed to the same reflux associated inflammatory triggers, the immune response observed in RE is clearly distinct from that in SQ of BE. The differences in immune responses in BE tissue might contribute to its susceptibility for transformation into intestinal metaplasia. PMID:25170842

  15. Tight Junctions in Salivary Epithelium

    PubMed Central

    Baker, Olga J.

    2010-01-01

    Epithelial cell tight junctions (TJs) consist of a narrow belt-like structure in the apical region of the lateral plasma membrane that circumferentially binds each cell to its neighbor. TJs are found in tissues that are involved in polarized secretions, absorption functions, and maintaining barriers between blood and interstitial fluids. The morphology, permeability, and ion selectivity of TJ vary among different types of tissues and species. TJs are very dynamic structures that assemble, grow, reorganize, and disassemble during physiological or pathological events. Several studies have indicated the active role of TJ in intestinal, renal, and airway epithelial function; however, the functional significance of TJ in salivary gland epithelium is poorly understood. Interactions between different combinations of the TJ family (each with their own unique regulatory proteins) define tissue specificity and functions during physiopathological processes; however, these interaction patterns have not been studied in salivary glands. The purpose of this review is to analyze some of the current data regarding the regulatory components of the TJ that could potentially affect cellular functions of the salivary epithelium. PMID:20182541

  16. miR-101 suppresses tumor proliferation and migration, and induces apoptosis by targeting EZH2 in esophageal cancer cells

    PubMed Central

    Lin, Chen; Huang, Fei; Li, Qiao-Zhi; Zhang, Ya-Jing

    2014-01-01

    Aim: To investigate the role of miR-101 in the regulation of tumor proliferation, invasion, apoptosis and to its target gene in human ESCC. Methods: The expression level of miR-101 in Eca109 cell line was determined by real-time polymerase chain reaction (PCR). After transfected with miR-101 mimics and inhibitor, proliferation, migration and apoptosis in ESCC cell line (Eca109) were detected by MTT, cell wound healing assay and flow cytometry, respectively. The expression of EZH2 in Eca109 cell was examined by immunohistochemical staining. Results: We found that miR-101 was significantly down-regulated in ESCC cell than in matched normal esophageal epithelium cell. The expression level of miR-101 was inversely correlated to EZH2 protein expression in ESCC cell. In Eca109 cells, over-expression of miR-101 significantly inhibited the migration and invasion of ESCC cells, and promotes cell apoptosis. Conclusions: These findings suggest that decreased expression of miR-101 might promote metastasis of human ESCC by inducing accumulation of EZH2 protein. PMID:25400732

  17. Photodynamic therapy for esophageal cancer

    PubMed Central

    Hatogai, Ken; Morimoto, Hiroyuki; Yoda, Yusuke; Kaneko, Kazuhiro

    2014-01-01

    Photodynamic therapy (PDT) is a treatment that uses a photosensitizing drug that is administered to the patient, localized to a tumor, and then activated with a laser to induce a photochemical reaction to destroy the cell. PDT using porfimer sodium followed by excimer dye laser irradiation is approved as a curative treatment for superficial esophageal cancer in Japan. While endoscopic submucosal dissection (ESD) is currently more popular for esophageal cancer, there is evidence to support PDT as an alternative treatment and as a salvage treatment for local failure after chemoradiotherapy (CRT). A photosensitizing agent has also been developed that requires a shorter sun shade period after administration, and studies are currently underway to establish an esophageal cancer indication for this next-generation PDT in Japan. PMID:25333005

  18. Environmental causes of esophageal cancer.

    PubMed

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

    2009-03-01

    This article reviews the environmental risk factors and predisposing conditions for the two main histologic types of esophageal cancer. Tobacco smoking, excessive alcohol consumption, drinking mat, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of esophageal squamous cell carcinoma. Results of investigations on 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 discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and, probably, absence of H pylori in the stomach increase the risk of esophageal adenocarcinoma. Results of studies investigating other factors are also discussed. PMID:19327566

  19. 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, Ren; 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

  20. Blunt Trauma Patient with Esophageal Perforation

    PubMed Central

    Oray, Nese C.; Sivrikaya, Semra; Bayram, Basak; Egeli, Tufan; Dicle, Oguz

    2014-01-01

    Traumatic perforation of the esophagus due to blunt trauma is a rare thoracic emergency. The most common causes of esophageal perforation are iatrogenic, and the upper cervical esophageal region is the most often injured. Diagnosis is frequently determined late, and mortality is therefore high. This case report presents a young woman who was admitted to the emergency department (ED) with esophageal perforation after having fallen from a high elevation. Esophageal perforation was diagnosed via thoracoabdominal tomography with ingestion of oral contrast. The present report discusses alternative techniques for diagnosing esophageal perforation in a multitrauma patient. PMID:25247037

  1. 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

  2. Dietary treatment of eosinophilic esophagitis.

    PubMed

    Gonsalves, Nirmala; Kagalwalla, Amir F

    2014-06-01

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

  3. Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin

    SciTech Connect

    Cenedella, R.J.; Fleschner, C.R. )

    1990-10-01

    The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea.

  4. Alterations of p53 and PCNA in cancer and adjacent tissues from concurrent carcinomas of the esophagus and gastric cardia in the same patient in Linzhou, a high incidence area for esophageal cancer in northern China

    PubMed Central

    Chen, Hong; Wang, Li-Dong; Guo, Mei; Gao, She-Gan; Guo, Hua-Qin; Fan, Zong-Min; Li, Ji-Lin

    2003-01-01

    AIM: To characterize the alteration and significance of p53 and PCNA in cancer and adjacent tissues of concurrent cancers from the esophagus and gastric cardia in the same patient. METHODS: P53 and PCNA protein accumulation in 25 patients with concurrent cancers from the esophagus and gastric cardia (CC, concurrent carcinomas of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma) were detected by immunohistochemical method (ABC). RESULTS: In CC patients, both esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA) tissues showed different positive immunostaining extent of p53 and PCNA protein (P > 0.05). The positive immunostaining rates for p53 and PCNA were 60% (15/25) and 92% (23/25), respectively in SCC; and 40% (10/25) and 88% (22/25), respectively in GCA. Diffuse immunostaining pattern was frequently observed in both p53 and PCNA. High coincidence rates for p53 and PCNA positive staining were observed in SCC and GCA from the same patients, and accounted for 56% and 96%. In SCC patients, with the lesions progressed from normal esophageal epithelium (NOR) to basal cell hyperplasia (BCH) to dysplasia (DYS) to carcinoma in situ (CIS) to SCC, the positive rates for p53 were 27%, 50%, 50%, 29% and 72%, and 55%, 70%, 75%, 71% and 93% for PCNA, respectively. In GCA, with the lesions progressed from normal gastric cardia epithelium to DYS to CIS to GCA, the positive rates of p53 expression were 44%, 27%, 22% and 36% respectively, the difference was not significant; the positive rates of PCNA protein expression were 67%, 64%, 67% and 86%, respectively. The ?2 test, Fishers Exact Test, Mantel-Haenszel ?2 Test and Kappa Test were used for the statistics. CONCLUSION: The high coincident alterations for P53 and PCNA in SCC and GCA from the same patient indicate the possibility of similar molecular basis, which provides important molecular basis and etiological clue for similar geographic distribution and risk factors in SCC and GCA. PMID:12508343

  5. Quantification of esophageal wall thickness in CT using atlas-based segmentation technique

    NASA Astrophysics Data System (ADS)

    Wang, Jiahui; Kang, Min Kyu; Kligerman, Seth; Lu, Wei

    2015-03-01

    Esophageal wall thickness is an important predictor of esophageal cancer response to therapy. In this study, we developed a computerized pipeline for quantification of esophageal wall thickness using computerized tomography (CT). We first segmented the esophagus using a multi-atlas-based segmentation scheme. The esophagus in each atlas CT was manually segmented to create a label map. Using image registration, all of the atlases were aligned to the imaging space of the target CT. The deformation field from the registration was applied to the label maps to warp them to the target space. A weighted majority-voting label fusion was employed to create the segmentation of esophagus. Finally, we excluded the lumen from the esophagus using a threshold of -600 HU and measured the esophageal wall thickness. The developed method was tested on a dataset of 30 CT scans, including 15 esophageal cancer patients and 15 normal controls. The mean Dice similarity coefficient (DSC) and mean absolute distance (MAD) between the segmented esophagus and the reference standard were employed to evaluate the segmentation results. Our method achieved a mean Dice coefficient of 65.55 10.48% and mean MAD of 1.40 1.31 mm for all the cases. The mean esophageal wall thickness of cancer patients and normal controls was 6.35 1.19 mm and 6.03 0.51 mm, respectively. We conclude that the proposed method can perform quantitative analysis of esophageal wall thickness and would be useful for tumor detection and tumor response evaluation of esophageal cancer.

  6. Expression of Cofilin-1 and Transgelin in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Zhang, Yan; Liao, Ruyi; Li, Hui; Liu, Ling; Chen, Xiao; Chen, Hongming

    2015-01-01

    Background Esophageal squamous cell carcinoma (ESCC) has attracted much research attention around the world, and the number of ESCC cases has increased gradually in recent years. Identifying the specific biomarkers of ESCC is an effective approach for the early diagnosis of tumors. Material/Methods Immunohistochemical streptavidin-peroxidase method was used to determine the expressions of Cofilin-1 and transgelin in 68 patients with esophageal squamous cell carcinoma (ESCC) and 48 individuals with normal esophageal tissues. In addition to the relationships between the expression of Cofilin-1 and transgelin, the clinicopathologic features of ESCC were also discussed. The correlation between Cofilin-1 and transgelin protein expression in ESCC was analyzed. Results (1) The positive expression rates of Cofilin-1 and transgelin were 60.3% (41/68) and 54.4% (37/68) in esophageal carcinoma tissue, respectively. The positive expression rates of Cofilin-1 and transgelin in normal esophageal tissue were 27.1% (13/48) and 29.1% (14/48), respectively. The differences were statistically significant (P<0.05). (2) The positive expression rate of Cofilin-1 did not differ significantly (P>0.05) with sex, age, ethnicity, tumor size, or infiltration depth; but did have a statistically significant (P<0.05) difference with various degrees of tumor differentiation, lymph node metastasis, and clinical stages. (3) The positive expression rate of transgelin did not differ significantly (P>0.05) with sex, age, ethnicity, tumor size, infiltration depth, and clinical stage, but did significantly (P<0.05) differ with degree of tumor differentiation and lymph node metastasis. Conclusions Cofilin-1 and transgelin may play roles in the carcinogenesis and development of esophageal squamous cell carcinoma. Cofilin-1 may be useful as an important biomarker for indicating the degree of malignancy of esophageal squamous cell carcinoma, and the detection of transgelin is valuable in early diagnosis of esophageal squamous cell carcinoma. PMID:26344167

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Expression of cytokeratins in the epithelium of canine odontogenic tumours.

    PubMed

    Arzi, B; Murphy, B; Nemec, A; Vapniarsky, N; Naydan, D K; Verstraete, F J M

    2011-11-01

    Odontogenic tumours are considered to be relatively rare; however, several histologically distinct types have been identified in dogs. The more common canine odontogenic tumours are peripheral odontogenic fibroma and canine acanthomatous ameloblastoma. The expression of cytokeratins (CKs) has been established for the human dental germ and odontogenic tumours. The aim of the present study was to describe the immunohistochemical expression of a panel of CKs in the epithelium of the canine dental germ, normal gingiva and odontogenic tumours arising in this species. Samples from 20 odontogenic tumours, 12 tooth germs and three normal gingival tissues were obtained. Each sample was stained with haematoxylin and eosin and subjected to immunohistochemistry for CK expression. The typical expression pattern of CKs in the odontogenic epithelium and gingiva of dogs was CK14 and CK5/6. CKs 7, 8, 18 and 20 were generally absent from the canine dental germ, gingiva and odontogenic tumours. Dogs and man therefore exhibit similar CK expression in the odontogenic epithelium. PMID:21511272

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

    ClinicalTrials.gov

    2015-12-09

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

  11. [Acute necrotizing esophagitis. Case report].

    PubMed

    Pierini, Angel; Imhof, Hugo; Burlando, Eduardo; Gianinetti, Leonardo; Pierini, Leandro

    2013-06-01

    Acute necrotizing esophagitis, also known as black esophagus, represents an extremely rare clinical entity, defined by the black pigmentation of the esophagus, secondary to necrosis of the mucosa and detected at endoscopy. We present a clinical case of this rare disease, with its manifestation, diagnosis, treatment, and we perform a review of the literature. PMID:23940914

  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. 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. PMID:21438963

  14. The clonal organization of the squamous epithelium of the tongue.

    PubMed

    Seddon, S V; Walker, D M; Williams, D; Williams, E D

    1992-03-01

    Knowledge of the kinetics and stem cell localization of the mouse lingual epithelium is largely based on studies using DNA labelling techniques. We have adopted a different approach, using histochemistry for the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD). We have deduced clone size and morphology from studies of patch size and distribution in mice heterozygous for G6PD deficiency and from the identification of clonal enzyme loss induced in normal mice by application of a mutagen. Lingual epithelium of female mice (CBA X GPDX) heterozygous for G6PD deficiency showed multiple clearly defined patches of strong or weak enzyme activity, corresponding in intensity to the strong staining uniformly present in the normal parental strain (CBA) or to the weak staining uniformly present in the G6PD deficient parental strain (GPDX). This pattern results from the random suppression of either the paternal or the maternal X chromosome in each cell early in embryonic development, and the subsequent inheritance of X inactivation in daughter cells, giving rise to phenotypic patches each composed of one or more clones. The patch borders intersected the base of the lingual epithelium at small indentations or at the apices of connective tissue papillae; the surface intersection in some cases bisected filiform papillae. Patch width measured in tissue sections at the mid rete ridge level, showed a clear mode close to 40 microns, corresponding very closely to the mode for rete ridge width (i.e. distance between connective tissue papillae). Further evidence for clonal organization was obtained by inducing mutations in the lingual epithelium of CBA mice by topical mutagen application. A few clearly defined patches of enzyme loss were found with a mean diameter of 36 microns. Their morphology was very similar to that of patches in the heterozygous animals. We interpret these patches as clones derived from stem cells with induced somatic G6PD mutations. We conclude that the mouse lingual epithelium is a stem cell epithelium composed of clonal units of about 40 microns diameter, based on the rete ridge structure and that both connective tissue papillae and filiform papillae occur at the junction of two or more epithelial clones. PMID:1554817

  15. TKTL1 promotes cell proliferation and metastasis in esophageal squamous cell carcinoma.

    PubMed

    Li, Juan; Zhu, Shu-Chai; Li, Shu-Guang; Zhao, Yan; Xu, Jin-Rui; Song, Chun-Yang

    2015-08-01

    Transketolase-like-1 (TKTL1), which is a rate-limiting enzyme in the non-oxidative part of the pentose-phosphate pathway, has been demonstrated to promote carcinogenesis through enhanced aerobic glycolysis. Dysregulation of TKTL1 expression also leads to poor prognosis in patients with urothelial and colorectal cancer. However, the expression pattern and underlying cellular functions in human esophageal squamous cell carcinoma (ESCC) remain largely unexplored. In this study, we measured TKTL1 expression in ESCC cell lines and paraffin-embedded ESCC tumor tissues. Our results revealed that TKTL1 expression was upregulated in all of the four ESCC cell lines and in 61.25% (98/160) of ESCC specimens detected, while only 27.5% (11/40) in normal epithelium. Silencing of TKTL1 expression decreased cell proliferation through inhibiting the expression of MKI67 and cyclins including Ccna2, Ccnb1, Ccnd1 and Ccne1. Meanwhile, down-regulation of TKTL1 also associated with increased apoptotic ratio and altered protein expression of Bcl-2 family in ESCC cells. Furthermore, knockdown of TKTL1 significantly reduced the invasive potential of ESCC cells through up-regulation of anti-metastasis genes (MTSS1, TIMP2 and CTSK) and down-regulation of pr-metastasis genes (MMP2, MMP9, MMP10 and MMP13). Taken together, our results indicate that TKTL1 is associated with a more aggressive behavior in ESCC cells and suppresses its expression or enzyme activity might represents a potential target for developing novel therapies in human ESCCs. PMID:26349965

  16. 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

  17. Biochemical studies of the tracheobronchial epithelium

    SciTech Connect

    Mass, M.J.; Kaufman, D.G.

    1984-06-01

    Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins. Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. 94 references, 9 figures, 2 tables.

  18. Neuropilins: expression and roles in the epithelium

    PubMed Central

    Wild, Jonathan R L; Staton, Carolyn A; Chapple, Keith; Corfe, Bernard M

    2012-01-01

    Summary Initially found expressed in neuronal and then later in endothelial cells, it is well established that the transmembrane glycoproteins neuropilin-1 (NRP1) and neuropilin-2 (NRP2) play essential roles in axonal growth and guidance and in physiological and pathological angiogenesis. Neuropilin expression and function in epithelial cells has received little attention when compared with neuronal and endothelial cells. Overexpression of NRPs is shown to enhance growth, correlate with invasion and is associated with poor prognosis in various tumour types, especially those of epithelial origin. The contribution of NRP and its ligands to tumour growth and metastasis has spurred a strong interest in NRPs as novel chemotherapy drug targets. Given NRPs role as a multifunctional co-receptor with an ability to bind with disparate ligand families, this has sparked new areas of research implicating NRPs in diverse biological functions. Here, we review the growing body of research demonstrating NRP expression and role in the normal and neoplastic epithelium. PMID:22414290

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

    PubMed

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

    2016-04-01

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

  20. Voice evaluation of myomucosal shunt after total laryngectomy: comparison with esophageal speech.

    PubMed

    Brasnu, D; Strome, M; Buchman, L C; Pfauwadel, M C; Menard, M; Martinez, P; Laccourreye, H

    1989-01-01

    The vocal quality attained with a tracheoesophageal myomucosal shunt (MMS) as described by Strome was evaluated in four patients and compared with three esophageal speakers and two normal subjects. The patients with MMSs acquired speech sooner. Fundamental frequency, pitch, timbre, and melody were analyzed with computerized electroglottography and sonography. Intelligibility was deemed better after the MMS primarily because phonation time approximated that of normal speech, and this study suggests that, following total laryngectomy, the vocal quality achieved using the MMS is preferrable to that of esophageal speech. PMID:2764239

  1. Near-infrared confocal micro-Raman spectroscopy combined with PCA-LDA multivariate analysis for detection of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Chen, Long; Wang, Yue; Liu, Nenrong; Lin, Duo; Weng, Cuncheng; Zhang, Jixue; Zhu, Lihuan; Chen, Weisheng; Chen, Rong; Feng, Shangyuan

    2013-06-01

    The diagnostic capability of using tissue intrinsic micro-Raman signals to obtain biochemical information from human esophageal tissue is presented in this paper. Near-infrared micro-Raman spectroscopy combined with multivariate analysis was applied for discrimination of esophageal cancer tissue from normal tissue samples. Micro-Raman spectroscopy measurements were performed on 54 esophageal cancer tissues and 55 normal tissues in the 400-1750 cm-1 range. The mean Raman spectra showed significant differences between the two groups. Tentative assignments of the Raman bands in the measured tissue spectra suggested some changes in protein structure, a decrease in the relative amount of lactose, and increases in the percentages of tryptophan, collagen and phenylalanine content in esophageal cancer tissue as compared to those of a normal subject. The diagnostic algorithms based on principal component analysis (PCA) and linear discriminate analysis (LDA) achieved a diagnostic sensitivity of 87.0% and specificity of 70.9% for separating cancer from normal esophageal tissue samples. The result demonstrated that near-infrared micro-Raman spectroscopy combined with PCA-LDA analysis could be an effective and sensitive tool for identification of esophageal cancer.

  2. Electrical properties of an excitable epithelium

    PubMed Central

    1979-01-01

    The exumbrellar epithelium of the hydromedusa, Euphysa japonica, is composed of a single layer of broad (70 micrometers), thin (1--2 micrometers) cells which are joined by gap junctions and simple appositions. Although the epithelium lacks nerves, it is excitable; electrically stimulating the epithelium initiates a propagated action potential. The average resting potential of the epithelial cells is -46 mV. The action potential, recorded with an intracellular electrode, is an all-or-nothing, positive, overshooting spike. The epithelial cells are electrically coupled. The passive electrical properties of the epithelium were determined from the decrement in membrane hyperpolarization with distance from an intracellular, positive current source. The two-dimensional space constant of the epithelium is 1.3 mm, the internal longitudinal resistivity of the cytoplasm and intercellular junctions is 196 omega cm, and the resistivity of both apical and basal cell membranes is greater than 23 k omega cm2. Although the membrane resistivity is high, the transverse resistivity of the epithelium is quite low (7.5 omega cm2), indicating that the epithelium is leaky with a large, transverse, paracellular shunt. PMID:39970

  3. A rare cause of dysphagia: herpes simplex esophagitis.

    PubMed

    Lee, Bee; Caddy, Grant

    2007-05-21

    Herpes simplex esophagitis (HSE) is well documented in immunosuppressed patients. However, it is rare in the immunocompetent host. We present a case of HSE in a 21 year-old healthy lady who was admitted to our unit with dysphagia, odynophagia and chest pain. Clinical examination revealed mild epigastric tenderness and admission bloods including full blood picture, electrolytes and inflammatory markers were normal. She underwent an esophagogastroduodenoscopy (EGD) which revealed severe exudative, well-circumscribed ulcerations in her distal esophagus. Biopsies confirmed severe esophagitis with acute ulceration and subsequent polymerase chain reaction (PCR) confirmed herpes simplex virus (HSV) type 1. Subsequent assessment failed to identify an immune disorder. HSE should be suspected when faced with characteristic endoscopic findings, even if the patient is immunocompetent. When the diagnosis of HSE is confirmed, an immune deficiency should be sought. PMID:17569149

  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. The Kagoshima consensus on esophageal achalasia.

    PubMed

    Triadafilopoulos, G; Boeckxstaens, G E; Gullo, R; Patti, M G; Pandolfino, J E; Kahrilas, P J; Duranceau, A; Jamieson, G; Zaninotto, G

    2012-05-01

    Esophageal achalasia is a primary esophageal motility disorder characterized by lack of peristalsis and a lower esophageal sphincter that fails to relax appropriately in response to swallowing. This article summarizes the most salient issues in the diagnosis and management of achalasia as discussed in a symposium that took place in Kagoshima, Japan, in September 2010 under the auspices of the International Society for Diseases of the Esophagus. PMID:21595779

  6. Corrosive Esophagitis Caused by Ingestion of Picosulfate

    PubMed Central

    Seo, Jae Yong; Kang, Ho Suk; Kim, Seong Eun; Park, Ji Won; Moon, Sung Hoon; Kim, Jong Hyeok; Park, Choong Kee

    2015-01-01

    Corrosive esophagitis is characterized by caustic injury due to the ingestion of chemical agents, mainly alkaline substances such as detergents. Esophageal bleeding, perforation, or stricture can be worsened by high-degree corrosive esophagitis. Picosulfate is a commonly used laxative frequently administered for bowel preparation before colonoscopy or colon surgery. Picosulfate powder should be completely dissolved in water before ingestion because the powder itself may cause chemical burning of the esophagus and stomach. Here, we report a case of corrosive esophagitis due to the ingestion of picosulfate powder that was not completely dissolved in water. PMID:25674529

  7. Pathohistological changes of tracheal epithelium in laryngectomized patients.

    PubMed

    Rosso, Marinela; Prgomet, Drago; Marjanovi?, Ksenija; Puelji?, Silvija; Kraljik, Nikola

    2015-11-01

    Total laryngectomy results in a permanent disconnection of the upper and lower airways. Thus, the upper airways are bypassed and can no longer condition, humidify, and filter the inhaled air, leading to damage of the tracheobronchial epithelium. There is little scientific information available about the effects of tracheostoma breathing and the degree of mucosal damage in laryngectomized patients. The aims of this study were to determine the histopathologic findings and investigate the potential impact of using a heat and moisture exchanger (HME) on the tracheal epithelium in long-term tracheostomy patients. Tracheal mucosal biopsies were taken from a total of 70 patients. Specimens were stained with hematoxylin and eosin and examined by a light microscope. Normal pseudostratified ciliated columnar epithelium was found in only 9 (12.9%) cases; while, 17 (24.3%) cases had some degree of basal cell hyperplasia. Squamous metaplasia was the most common finding (50%). Pre-invasive lesions (mild and moderate squamous dysplasia) were found in only one patient who used an HME, and in eight (11.4%) non-users. Although the HME cannot completely restore the physiological functions of the upper respiratory track, it delivers a better quality of air to the lower airways and has a positive effect on tracheal mucosa. PMID:25399353

  8. Effect of carbonated drinks on wound healing of oral epithelium

    PubMed Central

    Fahim, Ayesha; Ilyas, Muhammad Sharjeel; Jafari, Fahim Haider; Farzana, Fauzia

    2015-01-01

    Background Carbonated drinks are the second most consumed non-alcoholic beverages in the world after tea. The effects of these drinks on hard tissues and vital organs of the body have been proved beyond doubt. This study, however, explains the effect of these drinks on wound healing of oral epithelium. Methods Thirty-six male Wistar rats were considered for the study. A circular wound of 3.0mm was created on the buccal mucosa of all animals and they were divided into two groups. Animals in group 1 were fed with chow pellet and water, while those in group 2 were fed with a commercially available carbonated drink instead of water. Six animals from each group were euthanized at 0, 7, and 21 days. Wound site was histologically assessed for differences in thickness and characteristics of the regenerating epithelium between two groups. Results There was a marked difference in the healing pattern between the two groups. Animals in group 1 showed a normal healing pattern at the end of day 21. In the group 2, the regenerated epithelium showed hyperplasia and hyperkeratosis along with acanthosis at the end of the experiment with a subsequent delayed inflammatory reaction at day 21. Conclusion Consumption of carbonated drinks can disrupt oral wound healing. The contents in carbonated drinks have a proinflammatory action on the soft tissue. Results suggest that epithelial changes seen in experimental group 2 could be a result of constant irritation by the acidic and fizzy nature of carbonated drinks. PMID:26937370

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

    SciTech Connect

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

    2012-04-01

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

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

    PubMed Central

    Antunes, Lus Carlos Moreira; Prolla, Joo Carlos; de Barros Lopes, Antonio; da Rocha, Marta Pires; Fagundes, Renato Borges

    2013-01-01

    AIM: To investigate the association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in southern Brazil. METHODS: We studied 189 esophageal samples from 125 patients from three different groups: (1) 102 biopsies from 51 patients with ESCC, with one sample from the tumor and another from normal esophageal mucosa distant from the tumor; (2) 50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma (HNSCC); and (3) 37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients, not exposed to smoking or alcohol consumption. Nested-polymerase chain reaction (PCR) with the MY09/11 and GP5/6 L1 primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks. All PCR reactions were performed with a positive control (cervicovaginal samples), with a negative control (Human Genomic DNA) and with a blank reaction containing all reagents except DNA. We took extreme care to prevent DNA contamination in sample collection, processing, and testing. RESULTS: The histological biopsies confirmed the diagnosis of ESCC in 52 samples (51 from ESCC group and 1 from the HNSCC group) and classified as well differentiated (12/52, 23.1%), moderately differentiated (27/52, 51.9%) or poorly differentiated (7/52, 13.5%). One hundred twenty-eight esophageal biopsies were considered normal (51 from the ESCC group, 42 from the HNSCC group and 35 from dyspeptic patients). Nine had esophagitis (7 from the HNSCC and 2 from dyspeptic patients). Of a total of 189 samples, only 6 samples had insufficient material for PCR analysis: 1 from mucosa distant from the tumor in a patient with ESCC, 3 from patients with HNSCC and 2 from patients without cancer. In 183 samples (96.8%) GAPDH, G3PDH and/or ?-globin were amplified, thus indicating the adequacy of the DNA in those samples. HPV DNA was negative in all the 183 samples tested: 52 with ESCC, 9 with esophagitis and 122 with normal esophageal mucosa. CONCLUSION: There was no evidence of HPV infection in different ESCC from southern Brazil. PMID:24151387

  11. 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

  12. Pradaxa-induced esophageal ulcer.

    PubMed

    Wood, Michele; Shaw, Paul

    2015-01-01

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

  13. Gene expression profile of human esophageal squamous carcinoma cell line TE-1

    PubMed Central

    Cai, Hong-Xing; Zhu, Zheng-Qiu; Sun, Xiao-Ming; Li, Zhou-Ru; Chen, Yan-Bo; Dong, Guo-Kai

    2015-01-01

    Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly causes of cancer worldwide. However, to date, the mechanisms underlying its pathogenesis remain unclear. The present study investigated the gene expression profile of human esophageal cancer cell line TE-1, a cell model for ESCC, to gain insight to the genetic regulation of this disease. Human esophageal cancer TE-1 cells and normal esophageal HET-1A cells were cultured for isolation of total RNA. Differential expression of RNA transcripts was assessed using the Agilent 444 K microarray, combined with real-time PCR (qRT-PCR) for validation. Classification and function of the differential genes were illustrated by bioinformatics processing including hierarchical clustering and gene ontology (GO) analysis. We identified 4,986 transcripts with differential expression (fold-change ?1.5, P<0.05), including 2,368 up-regulated and 2,618 down-regulated transcripts. GO analysis showed that the dysregulated transcripts were associated with biological process, cellular component, and molecular function. After bioinformatic analysis of significantly regulated signaling pathways, we found these transcripts may target 35 gene pathways, including p53 signaling, glioma, ubiquitin-mediated proteolysis, insulin signaling, cell cycle, inositol phosphate metabolism, mTOR signaling, and MAPK signaling. The differentially expressed transcripts were screened between the esophageal cancer cell line TE-1 and normal esophageal cell line HET-1A, as well as their target gene pathways. Further data mining is related to prevention and treatment of esophageal cancer. PMID:26550410

  14. 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.

  15. 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

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

    PubMed

    van Hoeij, Froukje B; Bredenoord, Albert J

    2016-01-31

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

  17. Prolonged esophagitis after primary dysfunction of the pyloric sphincter in the rat and therapeutic potential of the gastric pentadecapeptide BPC 157.

    PubMed

    Dobric, Ivan; Drvis, Petar; Petrovic, Igor; Shejbal, Drazen; Brcic, Luka; Blagaic, Alenka Boban; Batelja, Lovorka; Sever, Marko; Kokic, Neven; Tonkic, Ante; Zoricic, Ivan; Mise, Sandro; Staresinic, Mario; Radic, Bozo; Jakir, Ana; Babel, Jaksa; Ilic, Spomenko; Vuksic, Tihomir; Jelic, Ivan; Anic, Tomislav; Seiwerth, Sven; Sikiric, Predrag

    2007-05-01

    Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 microg/kg, 10 ng/kg, last application 24 h before assessment), or continuously in drinking water at 0.16 microg/ml, 0.16 ng/ml (12 ml/rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH2O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg/kg, intraperitoneally, once daily; 0.83 mg/ml in drinking water; 50 mg/kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats. PMID:17452811

  18. 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

  19. Light dosimetry calculations for esophageal photodynamic therapy using porfimer sodium

    NASA Astrophysics Data System (ADS)

    Jones, Linda R.; Preyer, Norris W., Jr.; Davis, Monica A.; Grimes, Carson; Edling, Kristie; Holdgate, Nicholas; Wallace, Michael B.; Wolfsen, Herbert C.

    2006-02-01

    Background: Photodynamic therapy using porfimer sodium (Ps-PDT) is approved for use in patients with Barrett's highgrade dysplasia and esophageal carcinoma. Ps-PDT light dosimetry, however, is critically important to treatment outcomes since insufficient ablation results in residual dysplasia and carcinoma while excessive treatment results in stricture formation. Aim: The aim of this study was to model esophageal PDT with optical absorption and scattering coefficients derived from an ex-vivo porcine multilayer esophagus model. Methods: Optical coefficients were derived for the mucosal and muscle layers of normal pig esophagus. The mucosal layer (mucosa, muscularis mucosa and submucosa) was separated from the muscle layer. Diffuse reflectance and transmittance were measured with an integrating sphere spectrophotometer. Absorption and reduced scattering coefficients were determined with the inverse adding doubling method. (Table not available in abstract, see pdf of paper) Multilayer Monte Carlo simulation and single-layer mathematical dosimetry equations were employed to model esophageal PDT with the derived coefficients. Porfimer sodium addition was modeled with an increase in both absorption and scattering. Depth of injury, assumed to require a threshold light dose, was estimated for various light doses commonly used in clinical practice. Depth of injury was then compared to clinical outcomes reported in the literature for various light doses.

  20. Teaching Normal Birth, Normally

    PubMed Central

    Hotelling, Barbara A

    2009-01-01

    Teaching normal-birth Lamaze classes normally involves considering the qualities that make birth normal and structuring classes to embrace those qualities. In this column, teaching strategies are suggested for classes that unfold naturally, free from unnecessary interventions. PMID:19436595

  1. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium.

    PubMed

    Grego-Bessa, Joaquim; Bloomekatz, Joshua; Castel, Pau; Omelchenko, Tatiana; Baselga, Jos; Anderson, Kathryn V

    2016-01-01

    Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis. PMID:26809587

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

    PubMed

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

    2013-12-01

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

  3. The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide kinase inhibitor PP121

    SciTech Connect

    Peng, Yi; Zhou, Yajuan; Cheng, Long; Hu, Desheng; Zhou, Xiaoyi; Wang, Zhaohua; Xie, Conghua; Zhou, Fuxiang

    2015-09-11

    Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings. - Highlights: • PP121 is cytotoxic against primary and established esophageal cancer cells. • PP121 induces caspase-3-dependnent apoptosis in esophageal cancer cells. • PP121 blocks Akt-mTOR activation in esophageal cancer cells. • PP121 inhibits NFκB activation, independent of Akt-mTOR blockage. • PP121 inhibits Eca-109 xenograft growth and Akt-mTOR/NFκB activation in vivo.

  4. Esophageal Cancer Dose Escalation Using a Simultaneous Integrated Boost Technique

    SciTech Connect

    Welsh, James; Palmer, Matthew B.; Ajani, Jaffer A.; Liao Zhongxing; Swisher, Steven G.; Hofstetter, Wayne L.; Allen, Pamela K.; Settle, Steven H.; Gomez, Daniel; Likhacheva, Anna; Cox, James D.; Komaki, Ritsuko

    2012-01-01

    Purpose: We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Methods and Materials: Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. Results: The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). Conclusions: The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.

  5. The Utility of Proton Beam Therapy with Concurrent Chemotherapy for the Treatment of Esophageal Cancers

    PubMed Central

    Lin, Steven H.

    2011-01-01

    The standard of care for the management of locally advanced esophageal cancers in the United States is chemotherapy combined with radiation, either definitively, or for those who could tolerate surgery, preoperatively before esophagectomy. Although the appropriate radiation dose remains somewhat controversial, the quality of the radiation delivery is critical for the treatment of esophageal cancer since the esophagus is positioned close to vital structures, such as the heart and lung. The volume and relative doses to these normal tissues affect acute and late term complications. Advances in radiation delivery from 2D to 3D conformal radiation therapy, to Intensity Modulated Radiation Therapy (IMRT) or charged particle therapy (carbon ion or proton beam therapy (PBT)), allow incremental improvements in the therapeutic ratio. This could have implications in non-cancer related morbidity for long term survivors. This article reviews the evolution in radiation technologies and the use of PBT with chemotherapy in the management of esophageal cancer. PMID:24213126

  6. A late diagnosed case of Spontaneous esophageal perforation in an elderly patient

    PubMed Central

    Wei, Lu; Wang, Fei; Chen, Shuyan

    2015-01-01

    Spontaneous esophageal perforation, also known as Boerhaave’s syndrome, is a rare but potentially life-threatening condition, especially in elderly patients with more complications, speedy development and higher mortality. Successful handling of the disease depends on a timely diagnosis and the appropriate choice of treatment. Unfortunately, late diagnosis is common because of the non-specific clinical presentation. We here present a 72-year-old patient of spontaneous esophageal perforation who complained of chest pain, but sharply deteriorated with septic shock. With a vomiting history and gastrointestinal-genic bacterium identified in the chest fluid, the patient was highly suspected for esophageal perforation, though the oral methylene blue test was negative for three times. The diagnosis was finally established by esophagoscopy on the 10th day. The perforation was successfully healed by active conservative management and the patient was discharged home on the 43rd day eating normal diet. PMID:26379988

  7. An Unusual Case of Spontaneous Esophageal Rupture after Swallowing a Boneless Chicken Nugget.

    PubMed

    Aga, Zeenia; Avelino, Jackie; Darling, Gail E; Leung, Jo Jo

    2016-01-01

    A 25-year-old previously healthy man presented to our Emergency Department with shortness of breath and epigastric pain after swallowing a boneless chicken nugget one hour prior to presentation. Physical examination revealed epigastric rigidity and tenderness. Serology was normal except for mildly elevated bilirubin and amylase. Computed tomography (CT) scan of the chest revealed a distal esophageal rupture with accompanying pneumomediastinum and left-sided pleural effusion. Treatment was initiated with administration of intravenous fluids and broad-spectrum antibiotics. Subsequently, an esophageal stent was inserted endoscopically in addition to VATS (Video-Assisted Thoracoscopic Surgery) drainage of the left-sided pleural space. This case illustrates an unusual presentation of Boerhaave's syndrome: a rare and life-threatening form of noniatrogenic esophageal rupture most often preceded by forceful vomiting. Our case demonstrates that physicians should maintain an index of suspicion for spontaneous esophageal rupture in patients presenting with shortness of breath and epigastric pain even in the absence of preceding vomiting, cough, or seizure. Additionally, ingestion of boneless, shell-less foods may be sufficient to cause rupture in individuals without underlying esophageal pathology. CT scan of the thorax and upper abdomen should be performed in these patients to rule out this rare and life-threatening diagnosis. PMID:26949552

  8. An Unusual Case of Spontaneous Esophageal Rupture after Swallowing a Boneless Chicken Nugget

    PubMed Central

    Aga, Zeenia; Avelino, Jackie; Darling, Gail E.; Leung, Jo Jo

    2016-01-01

    A 25-year-old previously healthy man presented to our Emergency Department with shortness of breath and epigastric pain after swallowing a boneless chicken nugget one hour prior to presentation. Physical examination revealed epigastric rigidity and tenderness. Serology was normal except for mildly elevated bilirubin and amylase. Computed tomography (CT) scan of the chest revealed a distal esophageal rupture with accompanying pneumomediastinum and left-sided pleural effusion. Treatment was initiated with administration of intravenous fluids and broad-spectrum antibiotics. Subsequently, an esophageal stent was inserted endoscopically in addition to VATS (Video-Assisted Thoracoscopic Surgery) drainage of the left-sided pleural space. This case illustrates an unusual presentation of Boerhaave's syndrome: a rare and life-threatening form of noniatrogenic esophageal rupture most often preceded by forceful vomiting. Our case demonstrates that physicians should maintain an index of suspicion for spontaneous esophageal rupture in patients presenting with shortness of breath and epigastric pain even in the absence of preceding vomiting, cough, or seizure. Additionally, ingestion of boneless, shell-less foods may be sufficient to cause rupture in individuals without underlying esophageal pathology. CT scan of the thorax and upper abdomen should be performed in these patients to rule out this rare and life-threatening diagnosis. PMID:26949552

  9. Timing and intensity of changes in FDG uptake with symptomatic esophagitis during radiotherapy or chemo-radiotherapy

    PubMed Central

    2014-01-01

    Purpose To study whether esophageal FDG activity changes by time of mid-course of fractionated radiotherapy (RT), and whether these changes are associated with radiation esophagitis in patients with non-small cell lung cancer (NSCLC). Methods Fifty patients with stage I-III NSCLC were enrolled prospectively and, all received ≥60 Gy RT. FDG-PET/CT scans were acquired prior to, and during-RT after delivery of 45 Gy. Normalized standardized uptake values (NSUV), defined by the esophageal maximum SUV relative to intravascular background level in the aortic arch, were sampled in the esophagus at the level of the primary tumor, sternal notch, aortic arch, carina, and gastro-esophageal junction. Symptomatic radiation esophagitis was defined as an event. Results Compared to baseline, esophageal NSUV increased significantly during-RT at the level of the primary tumor (1.09 ± 0.05 vs.1.28 ± 0.06, p = 0.001), but did not change at other levels in the esophagus. 16 patients had radiation esophagitis events and these patients had significantly higher during-RT to baseline NSUV ratios than those without esophagitis (1.46 ± 0.12, 95% CI 1.20-1.71; vs. 1.11 ± 0.05, 95% CI 1.01-1.21, p = 0.002). Maximum esophageal dose (p = 0.029), concurrent chemotherapy (p = 0.022) and esophageal FDG PET NSUV ratio (during-RT to baseline, p = 0.007), were independent factors associated with esophagitis and area under curves (AUC) were 0.76, 0.70 and 0.78, respectively. Combining esophageal maximum dose and FDG PET NSUV Ratio at the tumor level increased AUC to 0.85 (p = 0.016). Conclusion FDG uptake increased in esophagus during-RT and this increase may predict radiation esphagitis during later course of treatment. PMID:24467939

  10. Status of epigenetic chromatin modification enzymes and esophageal squamous cell carcinoma risk in northeast Indian population

    PubMed Central

    Singh, Virendra; Singh, Laishram C; Singh, Avninder P; Sharma, Jagannath; Borthakur, Bibhuti B; Debnath, Arundhati; Rai, Avdhesh K; Phukan, Rup K; Mahanta, Jagadish; Kataki, Amal C; Kapur, Sujala; Saxena, Sunita

    2015-01-01

    Esophageal cancer incidence is reported in high frequency in northeast India. The etiology is different from other population at India due to wide variations in dietary habits or nutritional factors, tobacco/betel quid chewing and alcohol habits. Since DNA methylation, histone modification and miRNA-mediated epigenetic processes alter the gene expression, the involvement of these processes might be useful to find out epigenetic markers of esophageal cancer risk in northeast Indian population. The present investigation was aimed to carryout differential expression profiling of chromatin modification enzymes in tumor and normal tissue collected from esophageal squamous cell carcinoma (ESCC) patients. Differential mRNA expression profiling and their validation was done by quantitative real time PCR and tissue microarray respectively. Univariate and multiple logistic regression analysis were used to analyze the epidemiological data. mRNA expression data was analyzed by Student t-test. Fisher exact test was used for tissue microarray data analysis. Higher expression of enzymes regulating methylation (DOT1L and PRMT1) and acetylation (KAT7, KAT8, KAT2A and KAT6A) of histone was found associated with ESCC risk. Tissue microarray done in independent cohort of 75 patients revealed higher nuclear protein expression of KAT8 and PRMT1 in tumor similar to mRNA expression. Expression status of PRMT1 and KAT8 was found declined as we move from low grade to high grade tumor. Betel nut chewing, alcohol drinking and dried fish intake were significantly associated with increased risk of esophageal cancer among the study subject. Study suggests the association of PRMT1 and KAT8 with esophageal cancer risk and its involvement in the transition process of low to high grade tumor formation. The study exposes the differential status of chromatin modification enzymes between tumor and normal tissue and points out that relaxed state of chromatin facilitates more transcriptionally active genome in esophageal carcinogenesis. PMID:26045981

  11. Interferon γ-Induced Nuclear Interleukin-33 Potentiates the Release of Esophageal Epithelial Derived Cytokines

    PubMed Central

    Shan, Jing; Oshima, Tadayuki; Wu, Liping; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

    2016-01-01

    Background Esophageal epithelial cells are an initiating cell type in esophageal inflammation, playing an essential role in the pathogenesis of gastroesophageal reflux disease (GERD). A new tissue-derived cytokine, interleukin-33 (IL-33), has been shown to be upregulated in esophageal epithelial cell nuclei in GERD, taking part in mucosal inflammation. Here, inflammatory cytokines secreted by esophageal epithelial cells, and their regulation by IL-33, were investigated. Methods In an in vitro stratified squamous epithelial model, IL-33 expression was examined using quantitative RT-PCR, western blot, ELISA, and immunofluorescence. Epithelial cell secreted inflammatory cytokines were examined using multiplex flow immunoassay. IL-33 was knocked down with small interfering RNA (siRNA) in normal human esophageal epithelial cells (HEECs). Pharmacological inhibitors and signal transducers and activators of transcription 1 (STAT1) siRNA were used to explore the signaling pathways. Results Interferon (IFN)γ treatment upregulated nuclear IL-33 in HEECs. Furthermore, HEECs can produce various inflammatory cytokines, such as IL-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in response to IFNγ. Nuclear, but not exogenous IL-33, amplified IFN induction of these cytokines. P38 mitogen-activated protein kinase (MAPK) and janus protein tyrosine kinases (JAK)/STAT1 were the common signaling pathways of IFNγ-mediated induction of IL-33 and other cytokines. Conclusions Esophageal epithelial cells can actively participate in GERD pathogenesis through the production of various cytokines, and epithelial-derived IL-33 might play a central role in the production of these cytokines. PMID:26986625

  12. [Diffuse esophageal leiomyomatosis. Apropos of 3 cases].

    PubMed

    Heloury, Y; Borgne, J L; Babut, J M; David, A; Guyot, C; Fremont, B; Le Neel, J C

    1990-01-01

    Three cases of diffuse esophageal leiomyomatosis are discussed. Two of these are familial one, the mother being affected. These familial cases can occur in association with Alport's syndrome. The occurrence of a case of esophageal leiomyomatosis imply a familial survey and the search of a renal or ocular disease. The surgical treatment of this affection in sub total oesophagectomy with esophageal substitution (with the colon especially). The long term prognosis is unknown, with the risk of renal failure if Alport's syndrome is associated or of other leiomyomatous localisation. PMID:2386998

  13. Photodynamic therapy of early esophageal cancer.

    PubMed

    Filonenko, Elena V; Sokolov, Victor V; Chissov, Valery I; Lukyanets, Evgeny A; Vorozhtsov, Georgy N

    2008-09-01

    In 1992-2006 at P.A. Hertsen Moscow Oncology Research Institute photodynamic therapy (PDT) was performed in 48 esophageal cancer patients (total 48 lesions). For PDT we used Russian photosensitizers (Photogem, Photosens, Radachlorin, Alasens), Russian diode lasers (Crystall) and endoscopic equipment. As a result of PDT complete regression was in 77% of esophageal cancer lesions, partial regression was in 23%. The follow-up period was 3-11 years. Median of survival was in 4.59 years of esophageal cancer patient. PMID:19356654

  14. Communication apprehension in esophageal and tracheoesophageal speakers.

    PubMed

    Byles, P L; Forner, L L; Stemple, J C

    1985-05-01

    A comparison of communication apprehension levels between a group of esophageal speakers and a group of tracheoesophageal (TEP) speakers was undertaken. Ten esophageal speakers and 10 tracheoesophageal speakers were given the Personal Report of Communication Apprehension (McCroskey, 1978) and also were rated on their degree of intelligibility. Results indicated no significant difference between the mean communication apprehension scores of the esophageal and TEP speakers. The majority of speakers in both groups were in the moderate to low range of communication apprehension. Results are compared with existing literature and related to clinical management considerations. PMID:3990256

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

    PubMed Central

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

    2015-01-01

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

  16. Ambulatory High Resolution Manometry, Lower Esophageal Sphincter Lift and Transient Lower Esophageal Sphincter Relaxation

    PubMed Central

    Mittal, Ravinder K.; Karstens, Anna; Leslie, Eric; Babaei, Arash; Bhargava, Valmik

    2011-01-01

    Introduction Lower esophageal sphincter (LES) lift seen on high resolution manometry (HRM) is a possible surrogate marker of the longitudinal muscle contraction of the esophagus. Recent studies suggest that longitudinal muscle contraction of the esophagus induces LES relaxation. Aim Our goal was to determine, 1) the feasibility of prolonged ambulatory HRM and 2) to detect LES lift with LES relaxation using ambulatory HRM color isobaric contour plots. Methods In vitro validation studies were performed to determine the accuracy of HRM technique in detecting axial movement of the LES. Eight healthy normal volunteers were studied using a custom designed HRM catheter and a 16 channel data recorder, in the ambulatory setting of subject’s home environment. Color HRM plots were analyzed to determine the LES lift during swallow-induced LES relaxation as well as during complete and incomplete transient LES relaxations. Results Satisfactory recordings were obtained for 16 hours in all subjects. LES lift was small (2 mm) in association with swallow-induced LES relaxation. LES lift could not be measured during complete transient LES relaxations (TLESR) because the LES is not identified on the HRM color isobaric contour plot once it is fully relaxed. On the other hand, LES lift, mean 7.6 ± 1.4 mm, range 6–12 mm was seen with incomplete TLESRs (n = 80). Conclusions Our study demonstrates the feasibility of prolonged ambulatory HRM recordings. Similar to a complete TLESR, longitudinal muscle contraction of the distal esophagus occurs during incomplete TLESRs, which can be detected by the HRM. Using prolonged ambulatory HRM, future studies may investigate the temporal correlation between abnormal longitudinal muscle contraction and esophageal symptoms. PMID:22074595

  17. Radioprotective Effects of Amifostine on Acute and Chronic Esophageal Injury in Rodents

    SciTech Connect

    Vujaskovic, Zeljko; Thrasher, Bradley A.; Jackson, Isabel L.; Brizel, Marla B.; Brizel, David M.

    2007-10-01

    Purpose: This study was performed to evaluate the protective benefit of amifostine against esophageal injury from fractionated radiation in a rodent model. Methods: Fractionated or sham esophageal irradiation was administered to Fisher-344 rats for 5 consecutive daily fractions of 9 Gy using 150 kV X-rays. Animals received an intraperitoneal injection of amifostine or placebo 30 min before each fraction. Histopathologic analyses for mucosal thickness, submucosal collagen deposition, activation of macrophages, oxidative stress and expression/activation of integrin{alpha}v{beta}6 and transforming growth factor (TGF)-{beta} were performed 5 days and 10 weeks after irradiation. Results: Pre-RT mean mucosal thickness was 35 {mu}m in both the placebo and the amifostine groups. Five days post-RT, mean mucosal thicknesses were 30 {mu}m in the placebo group versus 37 {mu}m in the amifostine group (p = 0.024). At 10 weeks post-RT, the group receiving amifostine experienced a significant decrease in tunica muscularis damage (p = 0.002), submucosal collagen deposition (p = 0.027), and macrophage accumulation (p = 0.026) when compared with the placebo group. The levels of immunoreactivity for oxidative stress, TGF-{beta}, and integrin{alpha}v{beta}6 were significantly decreased 10 weeks post-RT in the group receiving amifostine treatment compared with placebo group. Conclusions: This study demonstrates that amifostine given before each radiation fraction protects against acute and chronic esophageal injury in a rodent model. Protection of the mucosal epithelium integrity by amifostine prevents integrin{alpha}v{beta}6 expression which reduces TGF-{beta} activation and subsequent development of chronic esophageal injury in this model. Further investigation is necessary to determine the clinical relevance of these findings.

  18. In vitro reconstruction of human junctional and sulcular epithelium

    PubMed Central

    Dabija-Wolter, G; Bakken, V; Cimpan, M R; Johannessen, A C; Costea, D E

    2013-01-01

    BACKGROUND The aim of this study was to develop and characterize standardized in vitro three-dimensional organotypic models of human junctional epithelium (JE) and sulcular epithelium (SE). METHODS Organotypic models were constructed by growing human normal gingival keratinocytes on top of collagen matrices populated with gingival fibroblasts (GF) or periodontal ligament fibroblasts (PLF). Tissues obtained were harvested at different time points and assessed for epithelial morphology, proliferation (Ki67), expression of JE-specific markers (ODAM and FDC-SP), cytokeratins (CK), transglutaminase, filaggrin, and basement membrane proteins (collagen IV and laminin1). RESULTS The epithelial component in 3- and 5-day organotypics showed limited differentiation and expressed Ki-67, ODAM, FDC-SP, CK 8, 13, 16, 19, and transglutaminase in a similar fashion to control JE samples. PLF supported better than GF expression of CK19 and suprabasal proliferation, although statistically significant only at day 5. Basement membrane proteins started to be deposited only from day 5. The rate of proliferating cells as well as the percentage of CK19-expressing cells decreased significantly in 7- and 9-day cultures. Day 7 organotypics presented higher number of epithelial cell layers, proliferating cells in suprabasal layers, and CK expression pattern similar to SE. CONCLUSION Both time in culture and fibroblast type had impact on epithelial phenotype. Five-day cultures with PLF are suggested as JE models, 7-day cultures with PLF or GF as SE models, while 9-day cultures with GF as gingival epithelium (GE) models. Such standard, reproducible models represent useful tools to study periodontal bacteria–host interactions in vitro. PMID:22947066

  19. Response of esophageal cancer cells to epigenetic inhibitors is mediated via altered thioredoxin activity.

    PubMed

    Ahrens, Theresa D; Timme, Sylvia; Ostendorp, Jenny; Bogatyreva, Lioudmilla; Hoeppner, Jens; Hopt, Ulrich T; Hauschke, Dieter; Werner, Martin; Lassmann, Silke

    2016-03-01

    We previously showed that histone deacetylase inhibitor (HDACi) and 5-azacytidine (AZA) treatment selectively induced cell death of esophageal cancer cells. The mechanisms of cancer selectivity, however, remained unclear. Here we examined whether the cancer selectivity of HDACi/AZA treatment is mediated by the thioredoxin (Trx) system and reactive oxygen species (ROS) in esophageal cancer cells. For this, we first analyzed human tissue specimens of 37 esophageal cancer patients by immunohistochemistry for Trx, Trx-interacting protein (TXNIP) and Trx reductase (TXNRD). This revealed a loss or at least reduction of nuclear Trx in esophageal cancer cells, compared with normal epithelial cells (P<0.001). Although no differences were observed for TXNIP, TXNRD was more frequently expressed in cancer cells (P<0.001). In the two main histotypes of esophageal squamous cell carcinomas (ESCCs, n=19) and esophageal adenomcarcinomas (EAC, n=16), similar Trx, TXNIP and TXNRD expression patterns were observed. Also in vitro, nuclear Trx was only detectable in non-neoplastic Het-1A cells, but not in OE21/ESCC or OE33/EAC cell lines. Moreover, the two cancer cell lines showed an increased Trx activity, being significant for OE21 (P=0.0237). After treatment with HDACi and/or AZA, ROS were exclusively increased in both cancer cell lines (P=0.048-0.017), with parallel decrease of Trx activity. This was variably accompanied by increased TXNIP levels upon AZA, MS-275 or MS-275/AZA treatment for 6 or 24?h in OE21, but not in Het-1A or OE33 cells. In summary, this study evaluated Trx and its associated proteins TXNIP and TXNRD for the first time in esophageal cancers. The analyses revealed an altered subcellular localization of Trx and strong upregulation of TXNRD in esophageal cancer cells. Moreover, HDACi and AZA disrupted Trx function and induced accumulation of ROS with subsequent apoptosis in esophageal cancer cells exclusively. Trx function is hence an important cellular mediator conferring non-neoplastic cell resistance for HDACi and/or AZA. PMID:26692290

  20. Cellular chloride and bicarbonate retention alters intracellular pH regulation in Cftr KO crypt epithelium.

    PubMed

    Walker, Nancy M; Liu, Jinghua; Stein, Sydney R; Stefanski, Casey D; Strubberg, Ashlee M; Clarke, Lane L

    2016-01-15

    Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR), an anion channel providing a major pathway for Cl(-) and HCO3 (-) efflux across the apical membrane of the epithelium. In the intestine, CF manifests as obstructive syndromes, dysbiosis, inflammation, and an increased risk for gastrointestinal cancer. Cftr knockout (KO) mice recapitulate CF intestinal disease, including intestinal hyperproliferation. Previous studies using Cftr KO intestinal organoids (enteroids) indicate that crypt epithelium maintains an alkaline intracellular pH (pHi). We hypothesized that Cftr has a cell-autonomous role in downregulating pHi that is incompletely compensated by acid-base regulation in its absence. Here, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein microfluorimetry of enteroids showed that Cftr KO crypt epithelium sustains an alkaline pHi and resistance to cell acidification relative to wild-type. Quantitative real-time PCR revealed that Cftr KO enteroids exhibit downregulated transcription of base (HCO3 (-))-loading proteins and upregulation of the basolateral membrane HCO3 (-)-unloader anion exchanger 2 (Ae2). Although Cftr KO crypt epithelium had increased Ae2 expression and Ae2-mediated Cl(-)/HCO3 (-) exchange with maximized gradients, it also had increased intracellular Cl(-) concentration relative to wild-type. Pharmacological reduction of intracellular Cl(-) concentration in Cftr KO crypt epithelium normalized pHi, which was largely Ae2-dependent. We conclude that Cftr KO crypt epithelium maintains an alkaline pHi as a consequence of losing both Cl(-) and HCO3 (-) efflux, which impairs pHi regulation by Ae2. Retention of Cl(-) and an alkaline pHi in crypt epithelium may alter several cellular processes in the proliferative compartment of Cftr KO intestine. PMID:26542396

  1. Expression of semaphorin 3A in the rat corneal epithelium during wound healing

    SciTech Connect

    Morishige, Naoyuki; Ko, Ji-Ae; Morita, Yukiko; Nishida, Teruo

    2010-05-14

    The neural guidance protein semaphorin 3A (Sema3A) is expressed in corneal epithelial cells of the adult rat. We have now further investigated the localization of Sema3A in the normal rat corneal epithelium as well as changes in its expression pattern during wound healing after central corneal epithelial debridement. The expression pattern of Sema3A was compared with that of the tight-junction protein zonula occludens-1 (ZO-1), the gap-junction protein connexin43 (Cx43), or the cell proliferation marker Ki67. Immunofluorescence analysis revealed that Sema3A was present predominantly in the membrane of basal and wing cells of the intact corneal epithelium. The expression of Sema3A at the basal side of basal cells was increased in the peripheral epithelium compared with that in the central region. Sema3A was detected in all layers at the leading edge of the migrating corneal epithelium at 6 h after central epithelial debridement. The expression of Sema3A was markedly up-regulated in the basal and lateral membranes of columnar basal cells apparent in the thickened, newly healed epithelium at 1 day after debridement, but it had largely returned to the normal pattern at 3 days after debridement. The expression of ZO-1 was restricted to superficial epithelial cells and remained mostly unchanged during the wound healing process. The expression of Cx43 in basal cells was down-regulated at the leading edge of the migrating epithelium but was stable in the remaining portion of the epithelium. Ki67 was not detected in basal cells of the central epithelium at 1 day after epithelial debridement, when Sema3A was prominently expressed. Immunoblot analysis showed that the abundance of Sema3A in the central cornea was increased 1 day after epithelial debridement, whereas that of ZO-1 or Cx43 remained largely unchanged. This increase in Sema3A expression was accompanied by up-regulation of the Sema3A coreceptor neuropilin-1. Our observations have thus shown that the expression of Sema3A is increased markedly in basal cells of the newly healed corneal epithelium, and that this up-regulation of Sema3A is not associated with cell proliferation. They further suggest that Sema3A might play a role in the regulation of corneal epithelial wound healing.

  2. Promoter hypermethylation and inactivation of O(6)-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines.

    TOXLINE Toxicology Bibliographic Information

    Fang MZ; Jin Z; Wang Y; Liao J; Yang GY; Wang LD; Yang CS

    2005-03-01

    The purpose of this study was to characterize the role of DNA hypermethylation in the loss of expression of O(6)-methylguanine-DNA methyltransferase (MGMT) during the development of esophageal squamous cell carcinoma (ESCC) and to investigate its reactivation in cell lines. Samples were collected from Linzhou City of the Henan province in northern China, a high-risk area of this disease. The hypermethylation of promoter CpG islands of the MGMT gene was examined by methylation-specific PCR in ESCC and neighboring non-tumorous tissues, as well as in laser capture microdissected samples with normal epithelium, basal cell hyperplasia (BCH), and dysplasia (DYS). The MGMT mRNA and protein expression were determined with RT-PCR and immunohistochemistry, respectively. Five of 17 (29%) normal, 10 of 20 (50%) BCH, 8 of 12 (67%) DYS, and 13 of 18 (72%) ESCC samples had DNA hypermethylation in the MGMT promoter region, showing a gradual increase with the progression of carcinogenesis. The frequency of the loss of MGMT mRNA and protein expression progressively decreased from normal to BCH, DYS, and ESCC, and it was highly correlated with MGMT promoter hypermethylation according to Fisher's exact tests. When each individual sample was considered, good concordance between DNA hypermethylation and the loss of expression of MGMT was also observed. In samples from the same patient, if hypermethylation was detected in earlier lesions, it was usually observed in more severe lesions. In the ESCC cell line KYSE 510, treatment with a DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine partially reversed the CpG hypermethylation status and restored mRNA expression of the MGMT gene. Similar reactivation of MGMT gene by dietary polyphenols, (-)-epigallocatechin-3-gallate and genistein, has also been observed. The results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing in the development of ESCC, and this epigenetic event may be prevented or reversed by these polyphenols for the prevention of carcinogenesis.

  3. Darier's Disease with Esophageal Involvement.

    PubMed

    Baba, Atsunori; Yonekura, Kentaro; Takeda, Koichiro; Kawai, Kazuhiro; Kanekura, Takuro

    2015-09-01

    We report the case of a Japanese man with Darier's disease (DD) that affected the esophagus as well as the skin. A 49-year-old man, who was diagnosed with DD 19 years earlier, visited us again in October 2008 because his skin lesions had exacerbated. Physical examination revealed reddish-brown crusted follicular papules mostly coalesced to produce irregularly-shaped warty plaques on his trunk, hip, upper and lower limbs, and scalp (Figure 1, a, b). Skin biopsy taken from the hip showed hyperkeratosis, papillomatosis, and suprabasal acantholysis with lacunae formation (Figure 1, c). The diagnosis of DD was confirmed and treatment with etretinate at 20 mg daily was started. The dose was increased to 50 mg 22 days later because his skin lesions failed to respond to the initial dose. When the dose was tapered to 20 mg after 2 months, painful erosions appeared on the hip. Tzanck smear testing showed balloon cells, and the serum level of Immunoglobulin M (IgM) antibody against herpes simplex virus (HSV) was elevated. The erosion was successfully treated with intravenous acyclovir (750 mg/day for 5 consecutive days). The oral administration of valaciclovir (500 mg/day) was continued as prophylaxis against the recurrence of HSV infection. While the disease was well managed with 20 mg etretinate/day, the patient experienced aggravation in April 2010 and painful swallowing in September 2010. Gastrointestinal endoscopy revealed multiple hyperkeratotic lesions in the middle of the esophagus (Figure 2, a). A biopsy showed histology similar to lesions on the skin including acantholysis and lacunae formation (Figure 2, b). Immunostaining did not detect either HSV-1, HSV-2, or human papilloma virus (HPV) in the esophageal mucosa. The skin lesions improved but the esophageal lesions persisted unchanged 8 months after increasing the daily dose of etretinate to 40 mg. DD is a rare autosomal dominant genodermatosis characterized by abnormal keratinization that primarily affects the skin. A total of 8 cases of DD affecting the esophagus have been reported previously (1-6). Several important issues emerged from our experience and literature review. Firstly, DD predisposes to infections with HSV, varicella-zoster virus (VZV), HPV, and pox virus (7,8). HSV infection was diagnosed in 1 of 8 previously-reported cases of esophageal DD. In one case, a 20-year-old man had severe thoracic pain; his esophageal lesion was immunohistochemically positive for HSV type I, and acyclovir treatment produced an early clinical response (6). In our case, HSV was detected in the cutaneous lesions but not the esophagus; esophageal lesions developed and persisted during the administration of acyclovir or valacicrovir. Although a partial immune-deficiency has been proposed as causative in some reports, no specific immune function anomaly has been demonstrated (6,7). It is possible that suprabasal acantholysis, a characteristic histological feature of DD, may provide a favorable environment for viral infections and result in innate host defense system deficiencies (8). Secondly, there is a hypothetical association between DD and malignant neoplasms. Among patients with DD, one patient with the esophageal form developed squamous cell carcinoma (SCC) (4). DD is attributed to a null-mutation in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) (9). The functional association of the ATP2A2 gene mutation with the development of SCC has been demonstrated. Mice with a single functional Atp2a2 allele, a mouse homolog of ATP2A2, manifested reduced levels of SERCA2; subsequent perturbations in calcium homeostasis or signaling served as a primary initiating event in the development of SCC. Heterozygous mutant Atp2a2 (+/-) mice developed SCC in the skin, oral mucosa, and esophagus where SERCA2 protein levels were decreased (10). We reported a rare case of DD with esophageal involvement and encourage dermatologists to be alert to viral infections and the possible development of cancer in patients with DD. PMID:26476908

  4. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    PubMed

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

    2016-02-01

    Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period. PMID:26772400

  5. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  6. 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

  7. Tissue engineering: an option for esophageal replacement?

    PubMed

    Zani, Augusto; Pierro, Agostino; Elvassore, Nicola; De Coppi, Paolo

    2009-02-01

    Esophageal replacement is required in several pediatric surgical conditions, like long-gap esophageal atresia. Although several techniques have been described to bridge the gap, all of them could be followed by postoperative complications. Esophageal tissue engineering could represent a valid alternative thanks to the recent advances in biomaterial science and cellular biology. Numerous attempts to shape a new esophagus in vitro have been described in the last decade. Herein, we review the main studies on the experimental use of nonabsorbable and absorbable materials as well as the development of cellularized patches. Furthermore, we describe the future perspectives of esophageal tissue engineering characterized by the use of stem cells seeded on new biopolymers. This opens to the construction of a functional allograft that could allow an anatomical replacement that grows with the children and does not severely impair their anatomy. PMID:19103424

  8. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  9. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  10. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  11. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  12. Magnetic lower esophageal sphincter augmentation device removal.

    PubMed

    Harnsberger, Cristina R; Broderick, Ryan C; Fuchs, Hans F; Berducci, Martin; Beck, Catherine; Gallo, Alberto; Jacobsen, Garth R; Sandler, Bryan J; Horgan, Santiago

    2015-04-01

    Implantation of a magnetic lower esophageal sphincter augmentation device is now an alternative to fundoplication in the surgical management of gastroesophageal reflux disease (GERD). Although successful management of GERD has been reported following placement of the device, there are instances when device removal is needed. The details of the technique for laparoscopic magnetic lower esophageal sphincter device removal are presented to assist surgeons should device removal become necessary. PMID:25119542

  13. Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

    PubMed Central

    LIU, JIAYI; LI, NING; LI, LI; LI, DANYE; LIU, KAI; ZHAO, LINGYUN; TANG, JINTIAN; LI, LIYA

    2013-01-01

    Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment. PMID:24260045

  14. Safe esophageal reconstruction by ileocolic interposition.

    PubMed

    Matsumoto, H; Hirai, T; Kubota, H; Murakami, H; Higashida, M; Hirabayashi, Y

    2012-04-01

    Many techniques have been proposed for esophageal reconstruction after esophagectomy when a gastric tube cannot be employed. There are two essential criteria for such a substitute: substitute length and sufficient blood supply. We propose ileocolic interposition as an easy and safe option. Two technical aspects contributing to the high success rate of this method are the preservation of an intact arterial network allowing normal blood flow to the ileocolic area, and the ability to quantify blood flow using a Doppler pulse flow meter in six cases. These are enabled by a long (up to 20cm) ileocolic segment. The preservation of the right colic artery is important, because its interruption would reduce blood supply to the long ileum segment. Between July 2003 and October 2008, we used this method in six patients in whom a gastric tube was not an option. We assessed perioperative morbidity and swallowing difficulties in each patient, quantifying dysphagia on scale of 0 to 4. There was no mortality and no anastomotic leak. There was one wound infection, and in one patient, recurrent nerve paralysis was observed. The postoperative hospital stay was 29.5 10.8 days. The average dysphagia score for the six patients was 0.17 0.41 after the operation. All patients can eat normally, without any dietary limitations. Ileocolonic interposition after esophagectomy requires careful assessment of the vascular supply. In this small series, morbidity was low and there was no perioperative mortality. We believe that this is an easy and safe method of reconstruction after esophagectomy in cases in whom a gastric tube cannot be used as a substitute. PMID:21819484

  15. Effect of nitrogen dioxide on human nasal epithelium

    SciTech Connect

    Carson, J.L.; Collier, A.M.; Hu, S.C.; Delvin, R.B. )

    1993-09-01

    The nasal epithelium of young adult white men in good health was evaluated by electron microscopy in a condition blind fashion relative to exposures of 2 ppm nitrogen dioxide (NO2) or clean air for 4 h. The exposure protocol involved two separate exposures of the same individuals to NO2 or clean air approximately 3 wk apart. We found qualitative and quantitative evidence that luminal border membranes of ciliated cells were ultrastructurally altered in six of seven samples of nasal epithelium obtained following NO2 exposures, although subsequent morphometric statistical analyses were not significant. This alteration was characterized by cilia containing excess matrix in which individual or, more commonly, multiple ciliary axonemes were embedded, and by vesiculations of luminal border ciliary membranes, a pattern less common in clean air-exposed control specimens. Although these patterns were not widespread, their morphology was consistent with findings of previous animal studies involving acute and chronic exposure to NO2. Our findings suggest that adverse effects on mucociliary function in normal humans due to acute exposure to low levels of NO2 are most likely minimal. However, in view of other reports of NO2 exposure in laboratory animals documenting ciliary injury, our observations support a view that similar patterns might appear more prominently with higher NO2 levels and/or more extended exposure intervals.

  16. Esophageal function after sclerotherapy of bleeding varices.

    PubMed

    Sauerbruch, T; Wirsching, R; Leisner, B; Weinzierl, M; Pfahler, M; Paumgartner, G

    1982-09-01

    To study the effect of sclerotherapy of varices on esophageal function, the motility of the tubular esophagus and of the lower esophageal sphincter (LES) were recorded in 19 patients after 7 to 13 sclerotherapy sessions and in 15 healthy volunteers. In addition, esophageal functional scintigraphy (EFS) was performed in the patient group. Compared with the volunteers the patients had lower contraction amplitudes in the distal esophagus (30.5 +/- 17.5 mm Hg versus 43.6 +/- 9.1 mm Hg, p less than 0.01) and a higher percentage of non-propulsive simultaneous contractions (NPC) in the distal (33.4 +/- 23.2% versus 9.0 +/- 8.6%, p less than 0.005) and mid-esophagus (15.0 +/- 8.2% versus 8.3 +/- 8.1%, p less than 0.05). There was a negative correlation between the percentage of NPC in the distal and mid-esophagus and radionuclide transit (rs - 0.53, p less than 0.02). Three of 19 patients had a positive reflux index by EFS. The LES tone was only slightly lower in the patients than in the controls (10.7 +/- 3.2 mm Hg versus 13.4 +/- 3.6 mm Hg, p less than 0.05). Our findings indicate that sclerotherapy of esophageal varices may lead to a reduced peristaltic esophageal motility with an impaired transport function. This could contribute to the development of dysphagia or esophagitis. PMID:6984219

  17. Obesity Is Associated With Increasing Esophageal Acid Exposure in Korean Patients With Gastroesophageal Reflux Disease Symptoms

    PubMed Central

    Jung, Hee Sun; Baeg, Myong Ki; Lim, Chul Hyun; Kim, Jin Soo; Cho, Yu Kyung; Lee, In Seok; Kim, Sang Woo; Choi, Kyu Yong

    2013-01-01

    Background/Aims Obesity is regarded as an important contributor to the increasing occurrence of gastroesophageal reflux disease. The aims of this study were to determine whether obesity is associated with gastroesophageal reflux in patients with gastroesophageal reflux disease and to identify the factors affecting increased acid exposure in obese patients. Methods We retrospectively analyzed the data of patients who underwent ambulatory 24-hour pH monitoring and esophageal manometry at Seoul St. Mary's Hospital. Obesity was classified according to the Asia-Pacific criteria. Results A total of 366 patients were analyzed; 18 were underweight, 152 normal weight, 104 overweight, and 92 obese. Obesity was more frequent in men and younger patients. The percentage time of pH < 4 in the total, upright, and postprandial periods was significantly higher in obese patients than in normal or underweight patients. The DeMeester score was also higher in obese patients. Body mass index correlated positively with reflux parameters. Multivariate analysis showed that being male and obesity were significantly associated with abnormal acid exposure (P < 0.005). The total lower esophageal sphincter length shortened as body mass index increased (P < 0.005). The gastroesophageal pressure gradient increased as body mass index increased (P < 0.05). Conclusions Obesity is associated with increasing esophageal acid exposure. The mechanism responsible for the relationship between gastroesophageal reflux disease and obesity may be associated with shortening of the lower esophageal sphincter length and increasing the gastroesophageal pressure gradient. PMID:23875101

  18. SOX2 Is an Amplified Lineage Survival Oncogene in Lung and Esophageal Squamous Cell Carcinomas

    PubMed Central

    Bass, Adam J.; Watanabe, Hideo; Mermel, Craig H.; Yu, Soyoung; Perner, Sven; Verhaak, Roel G.; Kim, So Young; Wardwell, Leslie; Tamayo, Pablo; Gat-Viks, Irit; Ramos, Alex H.; Woo, Michele S.; Weir, Barbara A.; Getz, Gad; Beroukhim, Rameen; OKelly, Michael; Dutt, Amit; Rozenblatt-Rosen, Orit; Dziunycz, Piotr; Komisarof, Justin; Chirieac, Lucian R.; LaFargue, Christopher J.; Scheble, Veit; Wilbertz, Theresia; Ma, Changqing; Rao, Shilpa; Nakagawa, Hiroshi; Stairs, Douglas B.; Lin, Lin; Giordano, Thomas J.; Wagner, Patrick; Minna, John D.; Gazdar, Adi F.; Zhu, Chang Qi; Brose, Marcia S.; Cecconello, Ivan; Ribeiro, Ulysses; Marie, Suely K.; Dahl, Olav; Shivdasani, Ramesh A.; Tsao, Ming-Sound; Rubin, Mark A.; Wong, Kwok K.; Regev, Aviv; Hahn, William C.; Beer, David G.; Rustgi, Anil K.; Meyerson, Matthew

    2009-01-01

    Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC. PMID:19801978

  19. Variations of gastric corpus microbiota are associated with early esophageal squamous cell carcinoma and squamous dysplasia

    PubMed Central

    Nasrollahzadeh, Dariush; Malekzadeh, Reza; Ploner, Alexander; Shakeri, Ramin; Sotoudeh, Masoud; Fahimi, Saman; Nasseri-Moghaddam, Siavosh; Kamangar, Farin; Abnet, Christian C.; Winckler, Bjrn; Islami, Farhad; Boffetta, Paolo; Brennan, Paul; Dawsey, Sanford M.; Ye, Weimin

    2015-01-01

    Observational studies revealed a relationship between changes in gastric mucosa and risk of esophageal squamous cell carcinoma (ESCC) which suggested a possible role for gastric microbiota in ESCC carcinogenesis. In this study we aimed to compare pattern of gastric corpus microbiota in ESCC with normal esophagus. Cases were included subjects with early ESCC (stage III) and esophageal squamous dysplasia (ESD) as the cancer precursor. Control groups included age and sex-matched subjects with mid-esophagus esophagitis (diseased-control), and histologically normal esophagus (healthy-control). DNA was extracted from snap-frozen gastric corpus tissues and 16S rRNA was sequenced on GS-FLX Titanium. After noise removal, an average of 3004 reads per sample was obtained from 93 subjects. We applied principal coordinate analysis to ordinate distances from beta diversity data. Pattern of gastric microbiota using Unifrac (p = 0.004) and weighted Unifrac distances (p = 0.018) statistically varied between cases and healthy controls. Sequences were aligned to SILVA database and Clostridiales and Erysipelotrichales orders were more abundant among cases after controling for multiple testing (p = 0.011). No such difference was observed between mid-esophagitis and healthy controls. This study is the first to show that composition of gastric corpus mucosal microbiota differs in early ESCC and ESD from healthy esophagus. PMID:25743945

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

    SciTech Connect

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

    2006-04-01

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

  1. Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer

    PubMed Central

    Hu, Bangli; Luo, Wei; Hu, Rui-Ting; Zhou, You; Qin, Shan-Yu; Jiang, Hai-Xing

    2015-01-01

    Abstract CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis. We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects. Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR?=?9.19, 95% CI?=?6.3013.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR?=?6.91, 95% CI?=?4.819.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR?=?2.47, 95% CI?=?1.563.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P?>?0.05). Moreover, no publication bias was found among the studies (all P?>?0.05). This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages. PMID:26252284

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

    SciTech Connect

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

    1991-06-01

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

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

    PubMed Central

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

    2014-01-01

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

  4. Value of two-phase dynamic multidetector computed tomography in differential diagnosis of post-inflammatory strictures from esophageal cancer

    PubMed Central

    Karmazanovsky, Grigory G; Buryakina, Svetlana A; Kondratiev, Evgeny V; Yang, Qin; Ruchkin, Dmitry V; Kalinin, Dmitry V

    2015-01-01

    AIM: To characterize the computed tomography (CT) findings in patients with post-inflammatory esophageal strictures (corrosive and peptic) and reveal the optimal scanning phase protocols for distinguishing post-inflammatory esophageal stricture and esophageal cancer. METHODS: Sixty-five patients with esophageal strictures of different etiology were included in this study: 24 patients with 27 histopathologically confirmed corrosive strictures, 10 patients with 12 peptic strictures and 31 patients with esophageal cancer were evaluated with a two-phase dynamic contrast-enhanced MDCT. Arterial and venous phases at 10 and 35 s after the attenuation of 200 HU were obtained at the descending aorta, with a delayed phase at 6-8 min after the start of injection of contrast media. For qualitative analysis, CT scans of benign strictures were reviewed for the presence/absence of the following features: “target sign”, luminal mass, homogeneity of contrast medium uptake, concentric wall thickening, conically shaped suprastenotic dilatation, smooth boundaries of stenosis and smooth mucous membrane at the transition to stenosis, which were compared with a control group of 31 patients who had esophageal cancer. The quantitative analysis included densitometric parameter acquisition using regions-of-interest measurement of the zone of stenosis and normal esophageal wall and the difference between those measurements (ΔCT) at all phases of bolus contrast enhancement. Esophageal wall thickening, length of esophageal wall thickening and size of the regional lymph nodes were also evaluated. RESULTS: The presence of a concentric esophageal wall, conically shaped suprastenotic dilatation, smooth upper and lower boundaries, “target sign” and smooth mucous membrane at the transition to stenosis were suggestive of a benign cause, with sensitivities of 92.31%, 87.17%, 94.87%, 76.92% and 82.05%, respectively, and specificities of 70.96%, 89.66%, 80.65%, 96.77% and 93.55%, respectively. The features that were most suggestive of a malignant cause were eccentric esophageal wall thickening, tuberous upper and lower boundaries of stenosis, absence of mucous membrane visualization, rupture of the mucous membrane at the upper boundary of stenosis, cup-shaped suprastenotic dilatation, luminal mass and enlarged regional lymph nodes with specificities of 92.31% 94.87%, 67.86%, 100%, 97.44%, 94.87% and 82.86%, respectively and sensitivities of 70.97%, 80.65%, 96.77%, 80.65%, 54.84%, 87.10% and 60%, respectively. The highest tumor attenuation occurred in the arterial phase (mean attenuation 74.13 ± 17.42 HU), and the mean attenuation difference between the tumor and the normal esophageal wall (mean ΔCT) in the arterial phase was 23.86 ± 19.31 HU. Here, 11.5 HU of ΔCT in the arterial phase was the cut-off value used to differentiate esophageal cancer from post-inflammatory stricture (P = 0.000). The highest attenuation of post-inflammatory strictures occurred in the delayed phase (mean attenuation 71.66 ± 14.28 HU), and the mean ΔCT in delayed phase was 34.03 ± 15.94 HU. Here, 18.5 HU of ΔCT in delayed phase was the cut-off value used to differentiate post-inflammatory stricture from esophageal cancer (P < 0.0001). CONCLUSION: The described imaging findings reveal high diagnostic significance in the differentiation of benign strictures from esophageal cancer. PMID:26269677

  5. Expression and mechanism of PinX1 and telomerase activity in the carcinogenesis of esophageal epithelial cells.

    PubMed

    Zuo, Jing; Wang, Da-Hu; Zhang, Yu-Jun; Liu, Liang; Liu, Feng-Ling; Liu, Wei

    2013-10-01

    Esophageal tissues were collected from an esophageal carcinoma high-risk area of China and were used to detect the telomere length and the expression of human telomerase reverse transcriptase (hTERT) by immuhistochemistry and fluorescence in situ hybridization; esophageal carcinoma tissues, paired-adjacent mucosa and paired normal mucosa were obtained from resected surgical specimens of esophageal squamous cell carcinoma in order to determine telomerase activity and expression of hTERT and Pin2/TRF1 interacting protein X1 (PinX1) by telomeric repeat amplification protocol-silver staining, RT-PCR and flow cytometry (FCM). The cell proliferation and apoptosis of Eca109 cells were analyzed by FCM and MTT assay. We found that the length of telomere DNA decreased and hTERT protein expression increased in the carcinogenesis of esophageal epithelial cells; telomerase activity was significantly upregulated followed by a decrease of PinX1 expression in esophageal carcinoma compared with dysplasia and normal patients, which notably correlated with grade and lymph node metastasis. Overexpression of PinX1 inhibited cell growth, arrested cells at the G0/G1 stage and induced cell apoptosis in Eca109 cells. In addition, PinX1 overexpression significantly inhibited telomerase activity. In conclusion, the length shortening of telomere was an important characteristic in the carcinogenesis of esophageal epithelial cells, followed by increase of telomerase activity and downregulation of PinX1. Overexpression of PinX1 blocked Eca109 cell proliferation and induced cell apoptosis by downregulating telomerase activity. PMID:23912465

  6. [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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  9. Poorer Black Patients Have Lower Survival from Esophageal Cancer

    MedlinePLUS

    ... nih.gov/medlineplus/news/fullstory_156988.html Poorer Black Patients Have Lower Survival From Esophageal Cancer Affluence ... 29, 2016 FRIDAY, Jan. 29, 2016 (HealthDay News) -- Blacks with low incomes who are diagnosed with esophageal ...

  10. Blunt traumatic esophageal injury: Unusual presentation and approach?

    PubMed Central

    Abdulrahman, Husham; Ajaj, Ahmad; Shunni, Adam; El-Menyar, Ayman; Chaikhouni, Amer; Al-Thani, Hassan; Latifi, Rifat

    2013-01-01

    INTRODUCTION Blunt esophageal injury is extremely rare event. However, it is a potential morbid injury unless managed early. PRESENTATION OF CASE We report a rare case of blunt esophageal injury for a 28-year old male who presented with history of fall of heavy object over the right side of the chest. Diagnostic work up including chest X-ray, computerized tomography scans and gastrografin esophagogram revealed lower esophageal rupture. Right mini-thoracotomy with esophageal repair was performed. Postoperative course was uneventful. DISCUSSION The exact mechanism of blunt esophageal injury remains uncertain. This report described a unique location of esophageal rupture after blunt trauma that happened on the right side. Diagnosis of esophageal injury needs high index of suspicion and accurate diagnostic workup. CONCLUSION Prompt diagnosis and management are the key for better prognosis in patients with blunt esophageal injury. PMID:24394856

  11. Odors Discrimination by Olfactory Epithelium Biosensor

    NASA Astrophysics Data System (ADS)

    Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping

    2011-09-01

    Humans are exploring the bionic biological olfaction to sense the various trace components of gas or liquid in many fields. For achieving the goal, we endeavor to establish a bioelectronic nose system for odor detection by combining intact bioactive function units with sensors. The bioelectronic nose is based on the olfactory epithelium of rat and microelectrode array (MEA). The olfactory epithelium biosensor generates extracellular potentials in presence of odor, and presents obvious specificity under different odors condition. The odor response signals can be distinguished with each other effectively by signal sorting. On basis of bioactive MEA hybrid system and the improved signal processing analysis, the bioelectronic nose will realize odor discrimination by the specific feature of signals response to various odors.

  12. Mechanically patterning the embryonic airway epithelium

    PubMed Central

    Varner, Victor D.; Gleghorn, Jason P.; Miller, Erin; Radisky, Derek C.; Nelson, Celeste M.

    2015-01-01

    Collections of cells must be patterned spatially during embryonic development to generate the intricate architectures of mature tissues. In several cases, including the formation of the branched airways of the lung, reciprocal signaling between an epithelium and its surrounding mesenchyme helps generate these spatial patterns. Several molecular signals are thought to interact via reaction-diffusion kinetics to create distinct biochemical patterns, which act as molecular precursors to actual, physical patterns of biological structure and function. Here, however, we show that purely physical mechanisms can drive spatial patterning within embryonic epithelia. Specifically, we find that a growth-induced physical instability defines the relative locations of branches within the developing murine airway epithelium in the absence of mesenchyme. The dominant wavelength of this instability determines the branching pattern and is controlled by epithelial growth rates. These data suggest that physical mechanisms can create the biological patterns that underlie tissue morphogenesis in the embryo. PMID:26170292

  13. Pigmented Lesions of the Retinal Pigment Epithelium.

    PubMed

    Ly, Angelica; Nivison-Smith, Lisa; Hennessy, Michael; Kalloniatis, Michael

    2015-08-01

    : The primary eye care practitioner assumes an important role in clinical decisions involving the differentiation between malignant and nonmalignant pigmented lesions. A misdiagnosis may have profound consequences on patient management and visual or life prognosis. However, information on these lesions, particularly their appearance using advanced imaging, is fragmented throughout the literature. The purpose of this review is to describe these features in detail, so that the implications of this information on clinical practice are more readily apparent. Clinically relevant descriptions of pigmented lesions of the retinal pigment epithelium using traditional and advanced imaging modalities in the literature were collated and integrated with findings from patients seen at the Centre for Eye Health. The information was then organized and tabulated. Finally, a flow diagram was created to be used as a clinical reference in the differential diagnosis of pigmented lesions of the retinal pigment epithelium. PMID:26099061

  14. Retinal pigment epithelium engineering using synthetic biodegradable polymers.

    PubMed

    Lu, L; Yaszemski, M J; Mikos, A G

    2001-12-01

    Retinal pigment epithelium (RPE) plays a key role in the maintenance of the normal functions of the retina, especially photoreceptors. Alteration in RPE structure and function is implicated in a variety of ocular disorders. Tissue engineering strategies using synthetic biodegradable polymers as temporary substrates for RPE cell culture and subsequent transplantation may provide a promising new therapy. In this review article, the manufacture of thin biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) films and their degradation behavior in vitro are discussed. RPE cell proliferation and differentiation on these PLGA films are reviewed. The fabrication of model substrates with desired chemical micropatterns in the micrometer scale is discussed and the effects of surface patterning on RPE morphology and function are assessed. Finally. the preparation of biodegradable micropatterns with adhesive PLGA and non-adhesive poly(ethylene glycol)/PLA domains to modulate RPE cell adhesion is presented. PMID:11700807

  15. X-ray microanalysis of hamster tracheal epithelium

    SciTech Connect

    Spencer, A.J.; Roomans, G.M. )

    1989-06-01

    Studies of ion transport across respiratory epithelia are of great interest if we are to understand the pathophysiology of diseases such as cystic fibrosis in which ion transport is abnormal. Concentrations of elements were determined in various subcellular regions of normal or isoproterenol-treated hamster tracheal epithelium, using X-ray microanalysis of freeze-dried cryosections. Samples of trachea were taken from animals under anesthesia and either frozen in situ or dissected and plunge frozen. Concentrations of Mg, P, S, Cl, K and Ca were higher in cytoplasm and nuclei of control epithelial cells in dissected samples than in cryoneedle samples. Following treatment with isoproterenol, a large decrease in the concentration of Cl was observed. The results confirm that cyclic AMP-regulated chloride secretion is unaffected by anesthesia.

  16. [The Buccal Epithelium as Environmental Indicator].

    PubMed

    Korsakov, A V; Yablokov, A V; Troshin, V P; Mikhalev, V P

    2015-01-01

    The use of the buccal mucosa cell micronucleus test for comparison of chemical, radiation, and radiation-chemical environmental pollution has been considered. The combined impact of chemical and radiation factors has been found to cause additive effects, synergism, and inhibition. It has been noted that the cytogenetic characteristics of the buccal epithelium may be used as a "biological dosimeter" of the total level of environmental pollution. PMID:26349240

  17. 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.

  18. Evaluation of urgent esophagectomy in esophageal perforation

    PubMed Central

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

    2014-01-01

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

  19. Morphological Alterations of the Palpebral Conjunctival Epithelium in a Dry Eye Model

    PubMed Central

    Henriksson, Johanna Tukler; De Paiva, Cintia S.; Farley, William; Pflugfelder, Stephen C.; Burns, Alan R.; Bergmanson, Jan P.G.

    2012-01-01

    Purpose To investigate the normal palpebral conjunctival histology in C57BL/6 mice, and the structural changes that occur in a dry eye model. Methods 24 male and female C57BL/6 mice, 8 untreated (UT) and 16 exposed to experimental ocular surface desiccating stress (DS). Ocular dryness was induced by administration of scopolamine hydrobromide (0.5 mg/0.2 ml) QID for 5 (DS5) or 10 (DS10) days. Counts and measurements were obtained using anatomical reference points and goblet cell density was investigated with a variety of stains. Results Near the junction between the lid margin and the normal palpebral conjunctiva, the epithelium had an average thickness of 45.6±10.5μm, 8.8±2.0 cell layers, versus 37.7±5.6μm, 7.4±1.3 layers in DS10 (P<0.05). In the goblet cell populated palpebral region the normal epithelium was thicker (P<0.05) than in DS5 and DS10. In the control, 43% of the goblet cells were covered by squamous epithelium, compared to 58% (DS5) and 63% (DS10) (P<0.05). A decreased number of Periodic Acid Schiff (PAS) and Alcian blue stained goblet cells was observed in the dry eye. Not all goblet cells stained with PAS and Alcian blue. Conclusions The mouse palpebral conjunctival epithelium was structurally similar to the human. After DS the palpebral conjunctival epithelium decreased in thickness and goblet cell access to the surface appeared to be inhibited by surrounding epithelial cells, potentially slowing down their migration to the surface. Differential staining with PAS and Alcian blue suggests there may be different subtypes of conjunctival goblet cells. PMID:23146932

  20. Broken Esophageal Stent Successfully Treated by Interventional Radiology Technique

    SciTech Connect

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

    2010-06-15

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

  1. Development of the ovarian follicular epithelium.

    PubMed

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women. PMID:10411332

  2. Progenitor Epithelium: Sorting Out Pancreatic Lineages.

    PubMed

    Marty-Santos, Leilani; Cleaver, Ondine

    2015-08-01

    Insulin-producing ? cells within the vertebrate fetal pancreas acquire their fate in a step-wise manner. Whereas the intrinsic factors dictating the transcriptional or epigenetic status of pancreatic lineages have been intensely examined, less is known about cell-cell interactions that might constitute a niche for the developing ? cell lineage. It is becoming increasingly clear that understanding and recapitulating these steps may instruct in vitro differentiation of embryonic stem cells and/or therapeutic regeneration. Indeed, directed differentiation techniques have improved since transitioning from 2D to 3D cultures, suggesting that the 3D microenvironment in which ? cells are born is critical. However, to date, it remains unknown whether the changing architecture of the pancreatic epithelium impacts the fate of cells therein. An emerging challenge in the field is to elucidate how progenitors are allocated during key events, such as the stratification and subsequent resolution of the pre-pancreatic epithelium, as well as the formation of lumens and branches. Here, we assess the progenitor epithelium and examine how it might influence the emergence of pancreatic multipotent progenitors (MPCs), which give rise to ? cells and other pancreatic lineages. PMID:26216134

  3. Deficiency of cell cycle checkpoints and DNA repair system predispose individuals to esophageal cancer.

    PubMed

    Shao, Lina; Hittelman, Walter N; Lin, Jie; Yang, Hushan; Ajani, Jaffer A; Wu, Xifeng

    2006-12-01

    Cell cycle checkpoints and DNA repair capacity are critical for the maintenance of genome integrity. We hypothesized that, in comparison to healthy controls, esophageal cancer patients might have a higher frequency of deficiencies in cell cycle checkpoints and/or DNA repair system. Using flow cytometry and comet assay, we assessed the gamma-radiation-induced S phase and G2-M phase accumulation, and benzo(a)pyrene-diol-epoxide (BPDE)- and gamma-radiation-induced DNA damage, in peripheral blood lymphocytes of 99 newly diagnosed esophageal cancer patients and 112 age-, gender-, and ethnicity-matched healthy controls. The mean gamma-radiation-induced cell accumulation at G2-M phase was significantly lower in esophageal cancer patients than the control subjects (case versus control: 5.27%+/-5.11% versus. 7.06%+/-5.04%, P = 0.013). The less G2-M phase cell accumulation resulted in a significant increased risk for esophageal cancer with an odds ratio of 2.08 (95% confidence interval 1.15-3.77). After normalization to baseline S fraction, the radiation-induced increment in the 4N/2N ratio was also significantly lower in esophageal cancer patients than in controls (case versus control: 0.76% versus 1.04%, P = 0.0039). The less increment in the radiation-induced 4N/2N ratio was associated with 2.24(95% confidence interval 1.22-4.11)-fold increase of esophageal cancer risk. We also compared the mutagen-induced DNA damage level among individuals with different S or G2-M phase cell accumulation. We found that the less G2-M phase accumulation was associated with both high BPDE induced and gamma-radiation-induced DNA damage in the healthy controls (P for trend = 0.023 and 0.015, respectively). Similar pattern was observed for S phase accumulation (P for trend = 0.033 and 0.022, respectively). However, such association was not seen in esophageal cancer patients. This study provides the first molecular epidemiologic evidence linking increased esophageal cancer risk with defects in cell-cycle checkpoints and DNA repair capacity. PMID:17011594

  4. Propagation of normal human epithelial cell populations using an in vivo culture system: description and applications

    SciTech Connect

    Klein-Szanto, A.J.P.; Terzaghi, M.; Mirkin, L.D.; Martin, D.; Shiba, M.

    1982-08-01

    A new model using xenotransplanted human epithelia was developed for the study of toxic and carcinogenic effects of chemicals. Epithelial cells from the respiratory tract of 4 male and 3 female premature and full-term fetuses were enzymatically removed and inoculated into deepithelialized rat tracheas. These were sealed at both ends and transplanted subcutaneously into nude mice. After 3 to 4 weeks, a normal mucociliary epithelium covered the tracheal lumen. At this stage the epithelial cells could be isolated again and transplanted into new denuded rat tracheas. This passaging could be repeated up to six times, each permitting an amplification factor of approximately 3. Tracheal transplants containing cells of human origin (in vivo Passages 2 to 4) were treated with 7,120dimethylbenz(a)anthracene. Hyperplasias, squamous metaplasias, and dysplasias were seen 1 to 8 weeks after initiation of treatment, indicating that the responses of human and rodent epithelial cells to polycyclic aromatic hydrocarbons are similar. Initial experiments with skin and esophageal epithelia suggest that other covering epithelia could also be used in this fashion for evaluation of toxicants and carcinogens that are likely to come into contact with these tissues.

  5. Treatment and long-term outcome of chronic radiation esophagitis after radiation therapy for head and neck tumors: A report of 13 cases

    SciTech Connect

    Silvain, C.; Barrioz, T.; Besson, I.; Babin, P.; Fontanel, J.P.; Daban, A.; Matuchansky, C.; Beauchant, M. )

    1993-05-01

    The natural history of chronic radiation esophagitis occurring in previously normal esophagus is still unknown. The authors describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2--120 months) after the end of radiation for pyriform fossae carcinoma (N = 5), tonsil carcinoma (N = 2), larynx carcinoma (N = 2), pharynx carcinoma (N = 2), base of the tongue (N = 1), and thyroid carcinomas (N = 1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and surgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatations. These treatments allowed nearly normal oral diet in 11/13 patients. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after six months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding. In conclusion, chronic radiation esophagitis is a severe disease with an underestimated frequency. In this study, peroral dilatations appeared to be necessary and were not associated with an increased morbidity. 21 refs., 1 tab.

  6. Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

    SciTech Connect

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

    2012-07-01

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

  7. Esophageal surgery in minimally invasive era.

    PubMed

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

    2016-01-27

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

  8. Esophageal surgery in minimally invasive era

    PubMed Central

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

    2016-01-01

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

  9. Esophageal Cancer: Insights From Mouse Models

    PubMed Central

    Ttreault, Marie-Pier

    2015-01-01

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

  10. Eosinophilic esophagitis: a bulk of mysteries.

    PubMed

    Straumann, Alex

    2013-01-01

    Eosinophilic esophagitis (EoE), which was first described in the early 1990s, has rapidly evolved as a distinctive chronic inflammatory esophageal disease. The diagnosis is based clinically on the presence of symptoms related to esophageal dysfunction and histologically by an eosinophil-predominant inflammation once other conditions leading to esophageal eosinophilia are excluded. This striking male-prevalent disease has an increasing incidence and prevalence in the Westernized countries. Currently, EoE represents the main cause of dysphagia and bolus impaction in adult patients. Despite the fact that EoE often occurs in atopic patients, the value of allergic testing is still under discussion. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically; they are therefore regarded as first-line drug therapy. Elimination diets have similar efficacy as topical corticosteroids, but their long-term use is limited by practical issues. Esophageal dilation of EoE-induced strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies have been fully defined. Currently, the list of unsolved issues--or mysteries--is still long and a concerted effort on behalf of clinicians and scientists is required to improve the understanding and the therapeutic management of this mysterious disease. PMID:23797116

  11. Esophageal tissue engineering: Current status and perspectives.

    PubMed

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

    2016-02-01

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

  12. Signal transduction in esophageal and LES circular muscle contraction.

    PubMed Central

    Harnett, K. M.; Cao, W.; Kim, N.; Sohn, U. D.; Rich, H.; Behar, J.; Biancani, P.

    1999-01-01

    Contraction of normal esophageal circular muscle (ESO) in response to acetylcholine (ACh) is linked to M2 muscarinic receptors activating at least three intracellular phospholipases, i.e., phosphatidylcholine-specific phospholipase C (PC-PLC), phospholipase D (PLD), and the high molecular weight (85 kDa) cytosolic phospholipase A2 (cPLA2) to induce phosphatidylcholine (PC) metabolism, production of diacylglycerol (DAG) and arachidonic acid (AA), resulting in activation of a protein kinase C (PKC)-dependent pathway. In contrast, lower esophageal sphincter (LES) contraction induced by maximally effective doses of ACh is mediated by muscarinic M3 receptors, linked to pertussis toxin-insensitive GTP-binding proteins of the G(q/11) type. They activate phospholipase C, which hydrolyzes phosphatidylinositol bisphosphate (PIP2), producing inositol 1,4,5-trisphosphate (IP3) and DAG. IP3 causes release of intracellular Ca++ and formation of a Ca++-calmodulin complex, resulting in activation of myosin light chain kinase and contraction through a calmodulin-dependent pathway. Signal transduction pathways responsible for maintenance of LES tone are quite distinct from those activated during contraction in response to maximally effective doses of agonists (e.g., ACh). Resting LES tone is associated with activity of a low molecular weight (approximately 14 kDa) pancreatic-like (group 1) secreted phospholipase A2 (sPLA2) and production of arachidonic acid (AA), which is metabolized to prostaglandins and thromboxanes. These AA metabolites act on receptors linked to G-proteins to induce activation of PI- and PC-specific phospholipases, and production of second messengers. Resting LES tone is associated with submaximal PI hydrolysis resulting in submaximal levels of inositol trisphosphate (IP3-induced Ca++ release, and interaction with DAG to activate PKC. In an animal model of acute esophagitis, acid-induced inflammation alters the contractile pathway of ESO and LES. In LES circular muscle, after induction of experimental esophagitis, basal levels of PI hydrolysis are substantially reduced and intracellular Ca++ stores are functionally damaged, resulting in a reduction of resting tone. The reduction in intracellular Ca++ release causes a switch in the signal transduction pathway mediating contraction in response to ACh. In the normal LES, ACh causes release of Ca++ from intracellular stores and activation of a calmodulin-dependent pathway. After esophagitis, ACh-induced contraction depends on influx of extracellular Ca++, which is insufficient to activate calmodulin, and contraction is mediated by a PKC-dependent pathway. These changes are reproduced in normal LES cells by thapsigargin-induced depletion of Ca++ stores, suggesting that the amount of Ca++ available for release from intracellular stores defines the signal transduction pathway activated by a maximally effective dose of ACh. PMID:10780577

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

    ClinicalTrials.gov

    2015-08-20

    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

  14. Endoscopic treatment of esophageal achalasia.

    PubMed

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

    2016-01-25

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

  15. Recent developments in esophageal adenocarcinoma.

    PubMed

    Lagergren, Jesper; Lagergren, Pernilla

    2013-01-01

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

  16. 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

  17. Overexpression of human ?-defensin 2 promotes growth and invasion during esophageal carcinogenesis

    PubMed Central

    Shi, Ni; Jin, Feng; Zhang, Xiaoli; Clinton, Steven K.; Pan, Zui; Chen, Tong

    2014-01-01

    Human ?-defensin 2 (HBD-2) is an antimicrobial peptide produced by mucosal surfaces in response to microbial exposure or inflammatory cytokines. Although HBD-2 is expressed in the esophagus in response to stress and infectious agents, little is known regarding its expression and functional role in esophageal carcinogenesis. In the current investigation, normal esophagus and N-nitrosomethylbenzylamine (NMBA)-induced precancerous and papillomatous lesions of the rat esophagus were characterized for HBD-2 encoding gene Defb4 and protein. HBD-2 was found to be overexpressed in esophagi of rats treated with NMBA compared to animals in control group. Results of Real-time PCR, Western blot and immunohistochemistry demonstrated a positive correlation between the overexpression of HBD-2 and the progression of rat squamous cell carcinogenesis (SCC) in the esophagus. We also observed that HBD-2 is overexpressed in tumor tissues removed from patients with esophageal SCC. Moreover, Defb4 silencing in vitro suppresses the tumor cell proliferation, mobility and invasion in esophageal SCC cell line KYSE-150. The results from this study provide experimental evidence that HBD-2 may play an oncogenic role in the initiation and progression of esophageal SCC and thus serves as a target for chemopreventive and therapeutic interventions. PMID:25226614

  18. Congenital esophageal stenosis owing to tracheobronchial remnants

    PubMed Central

    Rebelo, Priscila Guyt; Ormonde, Joo Victor C.; Ormonde, Joo 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 organ(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

  19. 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

  20. EXPRESSION OF PAX6 AND SOX2 IN ADULT OLFACTORY EPITHELIUM

    PubMed Central

    Guo, Zhen; Packard, Adam; Krolewski, Richard C.; Harris, Margaret T.; Manglapus, Glen L.; Schwob, James E.

    2010-01-01

    The olfactory epithelium maintains stem and progenitor cells that support the neuroepithelium’s life-long capacity to reconstitute after injury. However, the identity of the stem cells – and their regulation – remain poorly defined. The transcription factors Pax6 and Sox2 are characteristic of stem cells in many tissues, including the brain. Therefore, we assessed the expression of Pax6 and Sox2 in normal olfactory epithelium and during epithelial regeneration after methyl bromide lesion or olfactory bulbectomy. Sox2 is found in multiple kinds of cells in normal epithelium, including sustentacular cells, horizontal basal cells, and some globose basal cells. Pax6 is co-expressed with Sox2 in all these, but is also found in duct/gland cells as well as olfactory neurons that innervate necklace glomeruli. Most of the Sox2/Pax6-positive globose basal cells are actively cycling, but some express the cyclin-dependent kinase inhibitor p27Kip1, and are presumably mitotically quiescent. Among globose basal cells, Sox2 and Pax6 are co-expressed by putatively multipotent progenitors (labeled by neither anti-Mash1 nor anti-Neurog1) and neuron-committed transit amplifying cells (which express Mash1). However, Sox2 and Pax6 are expressed by only a minority of immediate neuronal precursors (Neurog1- and NeuroD1-expressing). The assignment of Sox2 and Pax6 to these categories of globose basal cells is confirmed by a temporal analysis of transcription factor expression during the recovery of the epithelium from methyl bromide-induced injury. Each of the Sox2/Pax6-colabeled cell types is at a remove from the birth of neurons; thus, suppressing their differentiation may be among the roles of Sox2/Pax6 in the olfactory epithelium. PMID:20852734

  1. Intracellular pigment epithelium-derived factor contributes to triglyceride degradation.

    PubMed

    Dai, Zhiyu; Zhou, Ti; Li, Cen; Qi, Weiwei; Mao, Yuling; Lu, Juling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Cai, Weibin; Yang, Zhonghan; Ma, Jianxing; Yang, Xia; Gao, Guoquan

    2013-09-01

    Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity. PMID:23886488

  2. Minimally invasive management of epiphrenic esophageal diverticula.

    PubMed

    Matthews, Brent D; Nelms, Cynthia D; Lohr, Charles E; Harold, Kristi L; Kercher, Kent W; Heniford, B Todd

    2003-06-01

    The purpose of this study is to review our initial experience with a minimally invasive approach to manage symptomatic epiphrenic esophageal diverticula. Five patients with symptomatic epiphrenic esophageal diverticula underwent surgical management between August 1997 and December 2002. All patients complained of dysphagia; had experienced symptoms for at least 12 months; and were evaluated preoperatively by a barium esophagram, esophagogastroduodenoscopy, and esophageal manometry. The epiphrenic esophageal diverticula measured 5 cm or less in all patients. Manometry demonstrated esophageal dysmotility in three patients. A minimally invasive technique was completed in all five patients. Four patients underwent laparoscopic diverticulectomy and myotomy including a concomitant Toupet fundoplication, and one patient underwent thoracoscopic diverticulectomy and myotomy. The mean operative time was 245 minutes (range 175-334). The longest operative time was for the thoracoscopic procedure. The estimated blood loss was minimal (range 30-100 cm3). The laparoscopic patients had a mean postoperative length of stay of 2.75 days (range 2-4) and the patient undergoing a thoracoscopic approach was discharged on postoperative day 6 due to a history of lung disease and home oxygen requirements. There were no other postoperative complications. After a mean follow-up of 16.2 months (range 3-36) all patients are asymptomatic. Short-term follow-up after our initial experience with minimally invasive approaches for epiphrenic esophageal diverticula demonstrates that thoracoscopic and laparoscopic approaches are feasible; safe; and effectively alleviate dysphagia, regurgitation, and other associated symptoms. Long-term outcomes should be monitored during the evolution of these novel minimally invasive techniques to ensure outcomes comparable to those of a transthoracic open approach. PMID:12852502

  3. Systematic review: Eosinophilic esophagitis in Asian countries

    PubMed Central

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Oshima, Naoki; Ishihara, Shunji

    2015-01-01

    AIM: To investigate the prevalence and the clinical characteristics of Asian patients with eosinophilic esophagitis. METHODS: We conducted a systematic search of the PubMed and Web of Science databases for original studies, case series, and individual case reports of eosinophilic esophagitis in Asian countries published from January 1980 to January 2015. We found 66 and 80 articles in the PubMed and Web of Science databases, respectively; 24 duplicate articles were removed. After excluding animal studies, articles not written in English, and meeting abstracts, 25 articles containing 217 patients were selected for analysis. RESULTS: Sample size-weighted mean values were determined for all pooled prevalence data and clinical characteristics. The mean age of the adult patients with eosinophilic esophagitis was approximately 50 years, and 73% of these patients were male. They frequently presented with allergic diseases including bronchial asthma, allergic rhinitis, food allergy, and atopic dermatitis. Bronchial asthma was the most frequent comorbid allergic disease, occurring in 24% of patients with eosinophilic esophagitis. Dysphagia was the primary symptom reported; 44% of the patients complained of dysphagia. Although laboratory blood tests are not adequately sensitive for an accurate diagnosis of eosinophilic esophagitis, endoscopic examinations revealed abnormal findings typical of this disease, including longitudinal furrows and concentric rings, in 82% of the cases. One-third of the cases responded to proton pump inhibitor administration. CONCLUSION: The characteristics of eosinophilic esophagitis in Asian patients were similar to those reported in Western patients, indicating that this disease displays a similar pathogenesis between Western and Asian patients. PMID:26217096

  4. Histomorphology and immunohistochemistry of the lower esophageal sphincter of the least shrew (Cryptotis parva).

    PubMed

    Al-Tikriti, Mohammed S; Khamas, Wael; Chebolu, Seetha; Darmani, Nissar A

    2013-01-01

    The biochemical and histopathological changes in the lower esophageal sphincter (LES) in the pathogenesis of gastroesophageal reflux disease have gained interest. The least shrew is able to vomit in response to emetogens and provides a good model to study the histology of this phenomenon relative to the published reports in the commonly used but vomit-incompetent laboratory species. The LES is located at the junction of the esophagus and stomach. It typically closes at rest and opens in response to swallowing. Our findings demonstrate that the least shrew does not have a well-defined LES, lacks esophageal glands and has a mucosal valve-like projection from the terminal end of the esophagus before joining the gastric epithelium at the lesser curvature. In addition, the least shrew has thoracic and abdominal components prior to joining the gastric epithelium. The mucosal lining of the esophagus is folded, becoming clearly convoluted and forming a bucket-like structure at the level of the esophageocardiac junction (ECJ). No significant differences are to be found between the structure and thickness of the wall before and after the ECJ. Thus, the ECJ forming the LES is relatively less complex than those of other mammals including man. The distribution of enterochromaffin (EC) cells is confined to the lamina propria of the junction and is not associated with the cardiac glands, suggesting its functional involvement with the smooth muscle in and around the ECJ. In conclusion, the least shrew's anatomical sphincter appears ill-defined and is replaced by a less sturdy valve-like mucosal flap. PMID:24662490

  5. Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model.

    PubMed

    Osei-Sarfo, Kwame; Urvalek, Alison M; Tang, Xiao-Han; Scognamiglio, Theresa; Gudas, Lorraine J

    2015-03-20

    Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often associated with alcohol and tobacco abuse. Because ESCCs exhibit high recurrence rates and are diagnosed at late stages, identification of prognostic and drug targets for prevention and treatment is critical. We used the 4-nitroquinoline-1-oxide (4-NQO) murine model of oral carcinogenesis and the Meadows-Cook model of alcohol abuse to assess changes in the expression of molecular markers during the initial stages of ESCC. Combining these two models, which mimic chronic alcohol and tobacco abuse in humans, we detected increased cellular proliferation (EGFR and Ki67 expression), increased canonical Wnt signaling and downstream elements (?-catenin, FoxM1, and S100a4 protein levels), changes in cellular adhesive properties (reduced E-cadherin in the basal layer of the esophageal epithelium), and increased levels of phosphorylated ERK1/2 and p38. Additionally, we found that treatment with ethanol alone increased the numbers of epithelial cells expressing solute carrier family 2 (facilitated glucose transporter, member 1) (SLC2A1) and carbonic anhydrase IX (CAIX), and increased the phosphorylation of p38. Thus, we identified both 4-NQO- and ethanol-specific targets in the initial stages of esophageal carcinogenesis, which should lead to the development of potential markers and therapeutic targets for human ESCC. PMID:25714027

  6. Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model

    PubMed Central

    Osei-Sarfo, Kwame; Scognamiglio, Theresa; Gudas, Lorraine J.

    2015-01-01

    Esophageal squamous cell carcinomas (ESCCs) are very common, aggressive tumors, and are often associated with alcohol and tobacco abuse. Because ESCCs exhibit high recurrence rates and are diagnosed at late stages, identification of prognostic and drug targets for prevention and treatment is critical. We used the 4-nitroquinoline-1-oxide (4-NQO) murine model of oral carcinogenesis and the Meadows-Cook model of alcohol abuse to assess changes in the expression of molecular markers during the initial stages of ESCC. Combining these two models, which mimic chronic alcohol and tobacco abuse in humans, we detected increased cellular proliferation (EGFR and Ki67 expression), increased canonical Wnt signaling and downstream elements (?-catenin, FoxM1, and S100a4 protein levels), changes in cellular adhesive properties (reduced E-cadherin in the basal layer of the esophageal epithelium), and increased levels of phosphorylated ERK1/2 and p38. Additionally, we found that treatment with ethanol alone increased the numbers of epithelial cells expressing solute carrier family 2 (facilitated glucose transporter, member 1) (SLC2A1) and carbonic anhydrase IX (CAIX), and increased the phosphorylation of p38. Thus, we identified both 4-NQO- and ethanol-specific targets in the initial stages of esophageal carcinogenesis, which should lead to the development of potential markers and therapeutic targets for human ESCC. PMID:25714027

  7. Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

    PubMed Central

    Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

    2011-01-01

    Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute to the development of ovarian cancer. PMID:21423607

  8. Ontogeny of the mouse vocal fold epithelium

    PubMed Central

    Lungova, Vlasta; Verheyden, Jamie M.; Herriges, John; Sun, Xin; Thibeault, Susan L.

    2015-01-01

    This investigation provides the first systematic determination of the cellular and molecular progression of vocal fold (VF) epithelium development in a murine model. We define five principal developmental events that constitute the progression from VF initiation in the embryonic anterior foregut tube to fully differentiated and functional adult tissue. These developmental events include (1) the initiation of the larynx and vocal folds with apposition of the lateral walls of the primitive laryngopharynx (embryonic (E) day 10.5); (2) the establishment of the epithelial lamina with fusion of the lateral walls of the primitive laryngopharynx (E11.5); (3) the epithelial lamina recanalization and separation of VFs (E13.5–18.5); (4) the stratification of the vocal folds (E13.5–18.5); and (5) the maturation of vocal fold epithelium (postnatal stages). The illustration of these morphogenetic events is substantiated by dynamic changes in cell proliferation and apoptosis, as well as the expression pattern of key transcription factors, FOXA2, SOX2 and NKX2-1 that specify and pattern the foregut endoderm. Furthermore, we documented the gradual conversion of VF epithelial cells from simple precursors expressing cytokeratins 8 and 18 in the embryo into mature stratified epithelial cells also expressing cytokeratins 5 and 14 in the adult. Interestingly, in the adult, cytokeratins 5 and 14 appear to be expressed in all cell layers in the VF, in contrast to their preferential localization to the basal cell layer in surrounding epithelium. To begin investigating the role of signaling molecules in vocal fold development, we characterized the expression pattern of SHH pathway genes, and how loss of Shh affects vocal fold development in the mutant. This study defines the cellular and molecular context and serves as the necessary foundation for future functional investigations of VF formation. PMID:25601450

  9. MicroRNAs and esophageal cancer

    PubMed Central

    Patnaik, Santosh Kumar; Mallick, Reema

    2010-01-01

    Cancer of the esophagus is a highly aggressive disease associated with an overall poor prognosis. There is an insistent need for improving our understanding of the molecular basis of this disease. The recent emergence of observations on the role of microRNAs in cancer and their potential as biomarkers has prompted many investigations to examine their relevance to esophageal cancer. This article provides an introduction to microRNA biology and the techniques involved in studying them, and summates what is now known about their role and utility in regard to neoplastic esophageal diseases. PMID:22811805

  10. Esophageal recurrence of medullary thyroid carcinoma

    PubMed Central

    Dworzynska, Agnieszka; Lorente-Poch, Leyre; Sancho, Juan Jose; Sitges-Serra, Antonio

    2015-01-01

    Medullary thyroid carcinoma (MTC) metastasizes to the regional lymph nodes and to the lungs, liver and bones. Only one case of recurrence of MTC involving the upper gastrointestinal tract has been reported so far. We describe the case of a 38-year-old woman with MTC, who developed an upper esophageal submucosal recurrence after two previous local recurrences treated surgically and one ethanol injection. After resection of the right lateral esophageal wall, calcitonin dropped by 60% and showed a doubling time >1 year. We cannot rule out the role of deep ethanol injection in the involvement of the cervical esophagus wall. PMID:26645011

  11. Prevalence of Barrett's Esophagus in first degree relatives of patients with esophageal adenocarcinoma

    PubMed Central

    Juhasz, Arpad; Mittal, Sumeet K; Lee, Tommy H; Deng, Caishu; Chak, Amitabh; Lynch, Henry T

    2011-01-01

    Aim Aim of this study is to determine the prevalence of Barrett's Esophagus (BE) in first degree relatives of patients with esophageal adenocarcinoma (EAC) and Barrett's' high grade dysplasia (HGD). Methods After Institutional Review board approval first degree relatives of patients with EAC/HGD underwent unsedated ultrathin trans-nasal endoscopy (UUTNE) with biopsy. BE was suspected if any salmon colored epithelial tongues were seen above the gastro-esophageal junction. A diagnosis of BE was made only if biopsy from these areas confirmed columnar lined epithelium with intestinal metaplasia. Results From 23 families 47 first degree relative underwent UUTNE and one patient underwent routine upper endoscopy with sedation as part of this study. The mean age of cases was 44.4 yrs. All patients tolerated the procedure well and there were no procedure related complications. BE was suspected in 16 (34%) patients and confirmed in 13/16 (27.7%) patients. There was 4 long segment (> 3cm) and 9 short segment (<3 cm) of BE. Conclusion There is a significantly higher than expected prevalence of BE in first degree relatives of EAC/HGD patients. This should be taken in to consideration to develop further screening guidelines. Further work is need to confirm these findings. Un-sedated trans-nasal endoscopy is a safe and well-tolerated method for BE screening. PMID:21617543

  12. Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.

    PubMed

    Horvay, Katja; Jard, Thierry; Casagranda, Franca; Perreau, Victoria M; Haigh, Katharina; Nefzger, Christian M; Akhtar, Reyhan; Gridley, Thomas; Berx, Geert; Haigh, Jody J; Barker, Nick; Polo, Jose M; Hime, Gary R; Abud, Helen E

    2015-05-12

    Snail family members regulate epithelial-to-mesenchymal transition (EMT) during invasion of intestinal tumours, but their role in normal intestinal homeostasis is unknown. Studies in breast and skin epithelia indicate that Snail proteins promote an undifferentiated state. Here, we demonstrate that conditional knockout of Snai1 in the intestinal epithelium results in apoptotic loss of crypt base columnar stem cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snai1 conditional knockout mice also undergo apoptosis when Snai1 is deleted. Conversely, ectopic expression of Snai1 in the intestinal epithelium in vivo results in the expansion of the crypt base columnar cell pool and a decrease in secretory enteroendocrine and Paneth cells. Following conditional deletion of Snai1, the intestinal epithelium fails to produce a proliferative response following radiation-induced damage indicating a fundamental requirement for Snai1 in epithelial regeneration. These results demonstrate that Snai1 is required for regulation of lineage choice, maintenance of CBC stem cells and regeneration of the intestinal epithelium following damage. PMID:25759216

  13. Morphological and Functional Features of Hepatic Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Alvaro, Domenico; Onori, Paolo; Alpini, Gianfranco; Franchitto, Antonio; Jefferson, Douglas M.; Torrice, Alessia; Cardinale, Vincenzo; Stefanelli, Fabrizio; Mancino, Maria Grazia; Strazzabosco, Mario; Angelico, Mario; Attili, Adolfo; Gaudio, Eugenio

    2008-01-01

    We evaluated the morphological and functional features of hepatic cyst epithelium in adult autosomal dominant polycystic kidney disease (ADPKD). In six ADPKD patients, we investigated the morphology of cyst epithelium apical surface by scanning electron microscopy and the expression of estrogen receptors (ERs), insulin-like growth factor 1 (IGF1), IGF1 receptors (IGF1-R), growth hormone receptor, the proliferation marker proliferating cell nuclear antigen, and pAKT by immunohistochemistry and immunofluorescence. Proliferation of liver cyst-derived epithelial cells was evaluated by both MTS proliferation assay and [3H]thymidine incorporation into DNA. The hepatic cyst epithelium displayed heterogeneous features, being normal in small cysts (<1 cm), characterized by rare or shortened cilia in 1- to 3-cm cysts, and exhibiting the absence of both primary cilia and microvilli in large cysts (>3 cm). Cyst epithelium showed marked immunohistochemical expression of ER, growth hormone receptor, IGF1, IGF1-R, proliferating cell nuclear antigen, and pAKT. IGF1 was 10-fold more enriched in the hepatic cyst fluid than in serum. Serum-deprived liver cyst-derived epithelial cells proliferated when exposed to 17?-estradiol and IGF1 and when exposed to human cyst fluid. ER or IGF1-R antagonists inhibited the proliferative effect of serum readmission, cyst fluid, 17?-estradiol, and IGF1. Our findings could explain the role of estrogens in accelerating the progression of ADPKD and may suggest a potential benefit of therapeutic strategies based on estrogen antagonism. PMID:18202196

  14. Asymmetric ( UC)albumin transport across bullfrog alveolar epithelium

    SciTech Connect

    Kim, K.J.; LeBon, T.R.; Shinbane, J.S.; Crandall, E.D.

    1985-10-01

    Bullfrog lungs were prepared as planar sheets and bathed with Ringer solution in Ussing chambers. In the presence of a constant electrical gradient (20, 0, or -20 mV) across the tissue, UC-labeled bovine serum albumin or inulin was instilled into the upstream reservoir and the rate of appearance of the tracer in the downstream reservoir was monitored. Two lungs from the same animal were used to determine any directional difference in tracer fluxes. An apparent permeability coefficient was estimated from a relationship between normalized downstream radioactivities and time. Results showed that the apparent permeability of albumin in the alveolar to pleural direction across the alveolar epithelial barrier is 2.3 X 10(-7) cm/s, significantly greater (P less than 0.0005) than that in the pleural to alveolar direction (5.3 X 10(-8) cm/s) when the tissue was short circuited. Permeability of inulin, on the other hand, did not show any directional dependence and averaged 3.1 X 10(-8) cm/s in both directions. There was no effect on radiotracer fluxes permeabilities of different electrical gradients across the tissue. Gel electrophoretograms and corresponding radiochromatograms suggest that the large and asymmetric isotope fluxes are not primarily due to digestion or degradation of labeled molecules. Inulin appears to traverse the alveolar epithelial barrier by simple diffusion through hydrated paracellular pathways. On the other hand, ( UC)albumin crosses the alveolar epithelium more rapidly than would be expected by simple diffusion. These asymmetric and large tracer fluxes suggest that a specialized mechanism is present in alveolar epithelium that may be capable of helping to remove albumin from the alveolar space.

  15. Gate-keeper function of the intestinal epithelium.

    PubMed

    Brandtzaeg, P

    2013-03-01

    There is currently a major focus on the role of the gut barrier function in balancing mucosal immune responses. Increased epithelial permeability for exogenous antigens is a crucial primary or secondary event in the pathogenesis of several disorders affecting body surfaces and beyond. The epithelial gate-keeper function is determined by the individual's age (e.g. preterm vs. term infant), diet, genetics, mucus composition, interactions between mast cells, nerves and neuropeptides, concurrent infection, the commensal microbiota and the epithelium-shielding effect of secretory IgA (SIgA) antibodies provided by breast milk or produced in the individual's gut. The integrity of the epithelial barrier furthermore depends on homeostatic regulatory mechanisms, including mucosal induction of regulatory T cells, where commensal microbiota-host interactions apparently play decisive roles. Thus, both extrinsic and intrinsic factors have been identified that may have an impact on the dynamics of the epithelial cell-cell junctions in the gut and thereby increase or reduce paracellular permeability. Experiments have shown that SIgA normally cooperates with innate defence factors to protect the epithelium and reinforce its barrier function. In the absence of SIgA commensal gut bacteria overstimulate innate epithelial immunity at the expense of expression of genes that regulate fat and carbohydrate metabolism, resulting in an epithelial gene signature that correlates with the development of lipid malabsorption. This shows that the intestinal epithelial barrier is a cross-road between defence and nutrition, and that SIgA is essential to keep the balance between these two functions. PMID:23257015

  16. Relationship among esophageal dysfunction, diabetic gastro-enteropathy, and autonomic neuropathy

    SciTech Connect

    Yeh, S.H.; Liu, R.S.; Wu, L.C.; Lin, H.D.; Wang, S.J.; Lin, W.H.

    1985-05-01

    This study assessed the relationship of esophageal radionuclide transit (RT) to diabetic gastroenteropethy (CEP) and autonomic neuropathy (AN). Data were acquired in list mode after an oral dose of 0.5 mCi Tc-99m sulfur colloid in 10 ml of water in the supine position. A modified computer routine was used to calculate: (A) total mean transit time (TMTT) in sec, (B) residual fraction after the first swallow (RF), and )C) retrograde index (RI). Twenty-one patients (pts) with diabetes and 25 normal subjects (N) were studied. Eleven pts belonged to Group 1 with symptomatic GEP and AN; 5, Group 2 with no GEP but with AN; and 5, Group 3 with neither. Abnormal RT mainly occurred in Group 1. RI was the best parameter with respective sensitivity and specificity of 0.91 (10/110 and 0.96 (24/25. RI was abnormal in 10/11 pts with GEP (Group 1), but normal in all 10 pts without GEP (Groups 2 and 3). All 5 pts only with AN (group 2) had normal RI. The authors conclude that esophageal dysfunction is present in nearly all pts with diabetic GEP. However, the presence of AN alone will not explain esophageal transit abnormality.

  17. Hereditary Factors in Esophageal Adenocarcinoma

    PubMed Central

    van Nistelrooij, Anna M.J.; Dinjens, Winand N.M.; Wagner, Anja; Spaander, Manon C.W.; van Lanschot, J. Jan B.; Wijnhoven, Bas P.L.

    2014-01-01

    Background The vast majority of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) cases are sporadic and caused by somatic mutations. However, over the last decades several families have been identified with clustering of EAC. Here, we review data from the published literature in order to address the current knowledge on familial EAC. Summary Although familial EAC comprises a relatively small group of patients, it is a clinically relevant category due to the poor prognosis of this type of cancer. Efforts should be made to identify specific genetic risk factors for familial EAC to enable identification of relatives at risk, since endoscopic surveillance can diagnose preneoplastic or early neoplastic lesions leading to early treatment, with improved outcome. Key Message Although familial EAC comprises a relatively small group of patients, this is a clinically relevant category due to the poor prognosis. Efforts should be made to identify specific genetic risk factors for familial EAC in order to facilitate the identification of other family members with a predisposition for this type of cancer. Practical Implications Approximately 7% of BE and EAC cases are considered familial. Age at diagnosis is generally lower for patients with familial EAC as compared to sporadic cases, while other known risk factors for EAC, such as male gender and Caucasian ethnicity, do not differ between the two groups. In several described families with clustering of EAC the pattern of inheritance seems to be consistent with a rare autosomal dominant genetic trait. However, some association has been found with (attenuated) familial adenomatous polyposis, mismatch repair deficiency and recently with the genes MSR1, ASCC1 and CTHRC1. Nevertheless, no specific genetic predisposition has yet been identified.

  18. Objectivity in the classification of tumours of the nasal epithelium

    PubMed Central

    Michaels, L.; Hyams, V. J.

    1975-01-01

    A survey of tumours derived from each of the four cell types of nasal epithelium is presented. Criticism is levelled at the adoption of additional terms for tissue types such as lympho-epithelium and transitional cell epithelium and tumours said to be derived from them. Electron microscopy is of assistance in classification particularly in the detection of evidence of keratin synthesis. The proposed classification of tumours of the nasal epithelium is: (1) Pseudostratified columnar epithelium: (a) papillary adenoma, (b) papillary carcinoma. (2) Squamous epithelium: (a) everted squamous papilloma, (b) inverted papilloma, (c) squamous carcinoma of any grade of differentiation from well differentiated to undifferentiated. (3) Melanocyte: malignant melanoma. (4) Olfactory neuroepithelium: olfactory neuroblastoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16Fig. 17Fig. 18Fig. 19Fig. 21Fig. 20 PMID:1197175

  19. Distinct microRNA expression profiles in follicle-associated epithelium and villous epithelium.

    PubMed

    Nakato, Gaku; Hase, Koji; Ohno, Hiroshi

    2015-09-01

    M cells in follicle-associated epithelium (FAE) covering intestinal lymphoid follicles serve as a portal of entry for particulate antigens (Kanaya and Ohno, 2014 [1]). Despite their biological significance, molecular mechanisms that govern M-cell differentiation and function have not been fully elucidated. MicroRNAs (miRNAs) have a role to control host gene expression profiles that modulate cellular physiology and characteristic. Many studies have shown that miRNAs regulate diverse biological processes including developmental timing, differentiation and growth control of cells and tissues (Ivey and Srivastava, 2010 [2]). miRNAs are also relevant to differentiation and function of intestinal epithelium (McKenna et al., 2010 [3]; Runtsch et al., 2014 [4]). Expression profiles and functions of miRNAs in the intestinal epithelium have been examined in jejunal and colonic mucosa [3]. In contrast, those in FAE remain uncharacterized. To address this deficiency, we isolated Peyer's Patch (PP) FAE and villous epithelium (VE) surrounding the FAE, and compared the miRNA expression profiles of FAE and VE by microarray analysis. This revealed that 43 miRNAs were up-regulated, whereas 9 miRNAs were down-regulated, in FAE compared to VE. A unique pattern of miRNA expression by FAE may reflect important diversity in cellular phenotypes and/or functional features of FAE. All microarray data has been deposited at GEO under accession number GSE46264. PMID:26484293

  20. IgG4-Related Esophageal Disease Presenting as Esophagitis Dissecans Superficialis With Chronic Strictures

    PubMed Central

    Dumas-Campagna, Myriam; Bouchard, Simon; Soucy, Genevieve; Bouin, Mickael

    2014-01-01

    IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmocytic infiltrate of IgG4-positive cells, storiform fibrosis and can be associated with tumefactive lesions. IgG4-related disease involving the upper gastrointestinal tract is rare and only two previous case reports have reported IgG4-related esophageal disease. We report the case of a 63-year-old female patient with a long-standing history of severe dysphagia and odynophagia with an initial diagnosis of reflux esophagitis. Symptoms persisted despite anti-acid therapy and control esophagogastroduodenoscopy (EGD) revealed endoscopic images consistent with esophagitis dissecans superficialis (sloughing esophagitis). An underlying autoimmune process was suspected and immunosuppressant agents were tried to control her disease. The patient eventually developed disabling dysphagia secondary to multiple chronic esophageal strictures. A diagnosis of IgG4-related disease was eventually made after reviewing esophageal biopsies and performing an immunohistochemical study with an anti-IgG4 antibody. Treatment attempts with corticosteroids and rituximab was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. Our case report describes this unique case of IgG4-related esophageal disease presenting as chronic esophagitis dissecans with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease. PMID:24883156

  1. 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?esophageal cancer had an 8-fold excess risk of ESCC (95%?CI: 1.74-36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio?=?1.91, 95%?CI: 1.54-2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

  2. Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma

    PubMed Central

    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]: 1.422.41), 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?esophageal cancer had an 8-fold excess risk of ESCC (95%?CI: 1.7436.32). 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: 1.542.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk. PMID:26526791

  3. Histatin-1 Expression in Human Lacrimal Epithelium

    PubMed Central

    Pasha, Zeeshan; Jaboori, Assraa Jassim; Jassim, Sarmad H.; Jain, Sandeep; Aakalu, Vinay K.

    2016-01-01

    Background Study of human lacrimal cell biology is limited by poor access to tissue samples, heterogeneous cell composition of tissue and a lack of established lacrimal epithelial markers. In order to further our understanding of lacrimal cell biology, we sought to find a better marker for human lacrimal epithelial cells, compared to what has been reported in the literature. Methods We utilized human Muller’s muscle conjunctival resection (MMCR) specimens containing accessory lacrimal gland (ALG) and cadaveric main lacrimal gland (MLG) as sources of lacrimal tissue. Candidate markers were sought using human ALG tissue from MMCR specimens, isolated by laser capture microdissection (LCM). Affymetrix® analysis was performed on total RNA isolated from FFPE samples to profile transcription in ALG. MMCR tissue sections were assessed by immunofluorescence using antibodies for histatin-1, lactoferrin, E-cadherin (E-cad) and alpha-smooth muscle actin (ASMA). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis was performed to analyze the expression of histatin-1, E-cad and lactoferrin from cadaveric MLG. Results Histatin-1 is expressed in ALG and MLG, localizes to lacrimal epithelium, and to a greater degree than do other putative lacrimal epithelial markers. Conclusions Histatin-1 is a good marker for human lacrimal epithelium in ALG and MLG and can be used to identify lacrimal cells in future studies. PMID:26824896

  4. Inter-observer Variability in Esophageal Body Measurements with High Resolution Manometry among New Physician Users

    PubMed Central

    Singh, Erick; Rife, Christopher; Clayton, Steven; Naas, Peter; Nietert, Paul; Castell, Donald

    2012-01-01

    Goals To evaluate inter-observer variability among four new physician users on measures of esophageal body function. Background Esophageal high resolution manometry (HRM) allows observation of esophageal motility via pressure topography plots. Little is known about the inter-observer variability among physicians. Study Two resident and two fellow level physicians each interpreted 10 liquid swallows of 20 esophageal HRM studies (n=200 swallows) using the BioVIEW Analysis Suite (Sandhill Scientific, Inc.). Studies evaluated were from patients referred for evaluation of dysphagia but found to have normal esophageal manometry and complete liquid bolus transit. Physicians received an orientation session and reviewed recent literature. Each physician recorded contractile front velocity (CFV) and distal contractile integral (DCI) for each liquid swallow. STATISTICS: Inter-observer agreements for CFV and DCI were assessed by intraclass correlation (ICC) values. Linear correlations between measurements by two readers were assessed using linear regression modeling techniques. Results CFV and DCI values of up to 200 data points were analyzed. Four reader results for CFV and DCI showed strong agreement although stronger for DCI measures (ICC=0.94; 0.91 - 0.98) in comparison to CFV (ICC=0.79; 0.52 - 0.82). Further correlation was performed with two readers; readers 1 and 2 revealed excellent correlation for DCI (r=0.95, p<0.001) and good correlation for CFV (r=0.61, p<0.001). Conclusions With a thorough orientation session, good to excellent agreement for CFV and DCI measurements can be obtained from new physician users. CFV measures exhibit greater inter-observer variability possibly due to the artifact produced by intraesophageal pressurization. PMID:22647828

  5. Local synthesis of pepsin in Barretts 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 Barretts biopsies from eight Barretts 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 Barretts, and four of eight adjacent normal specimens. Pepsinogen mRNA was observed in two Barretts, but not in normal adjacent samples. Pepsin induced PTSG2 (COX-2) and IL1? expression and cell migration in vitro. Conclusions Pepsin is synthesized by metaplastic, Barretts 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

  6. Oncogene GAEC1 regulates CAPN10 expression which predicts survival in esophageal squamous cell carcinoma

    PubMed Central

    Chan, Dessy; Tsoi, Miriam Yuen-Tung; Liu, Christina Di; Chan, Sau-Hing; Law, Simon Ying-Kit; Chan, Kwok-Wah; Chan, Yuen-Piu; Gopalan, Vinod; Lam, Alfred King-Yin; Tang, Johnny Cheuk-On

    2013-01-01

    AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was studied by using the RNA interference (RNAi) approach through transfecting the GAEC1-overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1-targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1-targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10) and upregulation of trinucleotide repeat containing 6C (TNRC6C) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 16.33 vs 12.62 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma. PMID:23687414

  7. Barretts and Esophageal Adenocarcinoma Consortium

    Cancer.gov

    An international consortium with epidemiologic studies of Barrett's Esophagus and esophageal adenocarcinoma. Analyses so far have included alcohol consumption, anthropometry, cigarette smoking, excess risk models, gastroesophageal reflux disease, non-steroidal anti-inflammatory drugs, reproductive factors, and genome-wide studies to identify susceptibility loci associated with Barretts esophagus and/or adenocarcinomas of the esophagus.

  8. A safe treatment option for esophageal bezoars

    PubMed Central

    Yaqub, Sheraz; Shafique, Muhammad; Kjæstad, Erik; Thorsen, Yngve; Lie, Erik S.; Dahl, Vegard; Bakka, Njål; Røkke, Ola

    2012-01-01

    INTRODUCTION Bezoar in the esophagus is a rare condition and associated with structural or functional abnormalities of the esophagus. Endoscopy is the main tool for diagnosis and treatment for bezoar in the esophagus. PRESENTATION OF CASE Here we present a case where an endoscopic evacuation of an esophageal bezoar was unsuccessful. We treated the bezoar through a nasogastric tube using a cocktail composed of pancreatic enzymes dissolved in Coca-Cola. DISCUSSION Endoscopy is regarded as the mainstay for the diagnosis and treatment of esophageal bezoars. However, when this approach fails, other treatment options include dissolution therapy, and surgical exploration and removal of the bezoar. Surgical removal of an esophageal bezoar is associated with a high risk of morbidity and mortality. We advocate that dissolving therapy should be the first choice of treatment when endoscopic evacuation is not possible. CONCLUSION This is the first report describing a successful treatment of an esophageal bezoar with a cocktail of Coca-Cola and pancreatic enzymes. It is an effective, inexpensive, and worldwide available treatment and should be considered when endoscopic evacuation fails. PMID:22609703

  9. Acute esophageal necrosis caused by alcohol abuse

    PubMed Central

    Endo, Tetsu; Sakamoto, Juichi; Sato, Ken; Takimoto, Miyako; Shimaya, Koji; Mikami, Tatsuya; Munakata, Akihiro; Shimoyama, Tadashi; Fukuda, Shinsaku

    2005-01-01

    Acute esophageal necrosis (AEN) is extremely rare and the pathogenesis of this is still unknown. We report a case of AEN caused by alcohol abuse. In our case, the main pathogenesis could be accounted for low systemic perfusion caused by severe alcoholic lactic acidosis. After the healing of AEN, balloon dilatation was effective to manage the stricture. PMID:16222758

  10. 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... enable the user to listen to heart and breath sounds. (b) Classification. Class I (general controls)....

  11. 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

  12. Esophageal testing: What we have so far.

    PubMed

    de Bortoli, Nicola; Martinucci, Irene; Bertani, Lorenzo; Russo, Salvatore; Franchi, Riccardo; Furnari, Manuele; Tolone, Salvatore; Bodini, Giorgia; Bolognesi, Valeria; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino; Savarino, Edoardo Vincenzo

    2016-02-15

    Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising. PMID:26909230

  13. [Esophageal foreign body revealed by respiratory distress].

    PubMed

    Chouaib, N; Rafai, M; Belyamani, L; Dimou, M; El Koraichi, A; El Haddoury, M; Ech-Cherif El Kettani, S

    2014-08-01

    Ingestion of a foreign body is usually accidental in children. Respiratory symptoms, often favored by the persistence of the foreign body in the esophagus, can be revealing, but rarely respiratory distress as a method telling. We report a case of unrecognized esophageal foreign body revealed by respiratory distress. PMID:24051189

  14. 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...

  15. Histomorphological and Immunophenotypic Features of Pill-Induced Esophagitis

    PubMed Central

    Kim, Su Hwan; Kim, Won; Lee, Kook Lae; Byeon, Sun-ju; Choi, Euno; Chang, Mee Soo

    2015-01-01

    The aim of this study was to investigate histomorphological and immunophenotypic features in pill-induced esophagitis. We comparatively evaluated the histomorphological, immunophenotypic features of pill-induced esophagitis vs. reflux esophagitis, as well as clinical information and endoscopic findings. Fifty-two tissue pieces from 22 cases of pill-induced esophagitis, 46 pieces from 20 reflux esophagitis, and 16 pieces from 14 control samples were subjected to immunohistochemistry for inflammatory infiltrates (CD3 for T lymphocyte, CD20 for B lymphocyte, CD56 for NK cell, CD68 for macrophage, CD117 for mast cell) and eosinophil chemotaxis-associated proteins (Erk, leptin, leptin receptor, pSTAT3, phospho-mTOR). As a result, Histomorphology showed that a diffuse pattern of dilated intercellular spaces was more frequently observed in pill-induced esophagitis, while reactive atypia and subepithelial papillary elongation were more often found in reflux esophagitis (P < 0.05, respectively). Interestingly, intraepithelial eosinophilic microabscess, intraepithelial pustule and diffuse pattern of dilated intercellular spaces were observed in 14% (3 cases), 9% (2 cases) and 32% (7 cases) of pill-induced esophagitis, respectively, but in no cases of reflux esophagitis. Regarding intraepithelial inflammatory infiltrates in pill-induced esophagitis, T lymphocytes were the most common cells, followed by eosinophil; 11 and 7 in one x400 power field, respectively. Intraepithelial pSTAT3-positive pattern was more frequently observed in pill-induced esophagitis than in reflux esophagitis, at 45% (10 cases) versus 10% (2 cases), respectively (P < 0.05). Considering the distal esophageal lesion only, intraepithelial pustule, diffuse dilated intercellular spaces and stromal macrophages were more frequently found in distal pill-induced esophagitis, whereas reactive atypia and intraepithelial mast cells in reflux esophagitis (P < 0.05, respectively). In conclusion, diffuse dilated intercellular spaces, intraepithelial eosinophil microabscess, pustule, T lymphocytes, eosinophils, and pSTAT3 positivity can be added to histopathological features of pill-induced esophagitis, other than non-specific ulcer. Besides, distal pill-induced esophagitis may be histopathologically differentiated from reflux esophagitis. PMID:26047496

  16. Supragastric Belching: Prevalence and Association With Gastroesophageal Reflux Disease and Esophageal Hypomotility

    PubMed Central

    Koukias, Nikolaos; Woodland, Philip; Yazaki, Etsuro; Sifrim, Daniel

    2015-01-01

    Background/Aims Supragastric belching (SGB) is a phenomenon during which air is sucked into the esophagus and then rapidly expelled through the mouth. Patients often complain of severely impaired quality of life. Our objective was to establish the prevalence of excessive SGB within a high-volume gastrointestinal physiology unit, and evaluate its association with symptoms, esophageal motility and gastresophageal reflux disease. Methods We established normal values for SGB by analyzing 24-hour pH-impedance in 40 healthy asymptomatic volunteers. We searched 2950 consecutive patient reports from our upper GI Physiology Unit (from 20102013) for SGB. Symptoms were recorded by a standardized questionnaire evaluating for reflux, dysphagia, and dyspepsia symptoms. We reviewed the predominant symptoms, 24-hour pH-impedance and high-resolution esophageal manometry results. Results Excessive SGB was defined as > 13 per 24 hours. We identified 100 patients with excessive SGB. Ninety-five percent of these patients suffered from typical reflux symptoms, 86% reported excessive belching, and 65% reported dysphagia. Forty-one percent of patients with excessive SGB had pathological acid reflux. Compared to the patients with normal acid exposure these patients trended towards a higher number of SGB episodes. Forty-four percent of patients had esophageal hypomotility. Patients with hypomotility had a significantly higher frequency of SGB compared to those with normal motility (118.3 106.1 vs 80.6 75.7, P = 0.020). Conclusions Increased belching is rarely a symptom in isolation. Pathological acid exposure and hypomotility are associated with more SGB frequency. Whether SGB is a disordered response to other esophageal symptoms or their cause is unclear. PMID:26130635

  17. Identification of a high-molecular-mass Lactobacillus epithelium adhesin (LEA) of Lactobacillus crispatus ST1 that binds to stratified squamous epithelium.

    PubMed

    Edelman, Sanna M; Lehti, Timo A; Kainulainen, Veera; Antikainen, Jenni; Kylväjä, Riikka; Baumann, Marc; Westerlund-Wikström, Benita; Korhonen, Timo K

    2012-07-01

    Lactobacilli belong to the normal gastrointestinal and genital tract microbiota of human and animal hosts. Adhesion is important for bacterial colonization; however, only a few Lactobacillus adhesins have been identified so far. We studied extracted surface proteins from an adhesive Lactobacillus crispatus strain, ST1, which efficiently colonizes the chicken alimentary tract, for their binding to tissue sections of the chicken crop, and identified a novel high-molecular-mass repetitive surface protein that shows specific binding to stratified squamous epithelium. The adhesin binds to both crop epithelium and epithelial cells from human vagina, and was named Lactobacillus epithelium adhesin (LEA). Expression of LEA is strain-specific among L. crispatus strains and corresponds directly to in vitro bacterial adhesion ability. The partial sequence of the lea gene predicts that the LEA protein carries an N-terminal YSIRK signal sequence and a C-terminal LPxTG anchoring motif, as well as a highly repetitive region harbouring 82 aa long repeats with non-identical sequences that show similarity to Lactobacillus Rib/alpha-like repeats. LEA-mediated epithelial adherence may improve bacterial colonization in the chicken crop and the human vagina, which are the natural environments for L. crispatus. PMID:22516222

  18. Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor

    PubMed Central

    Feng, Fan; Tian, Yangzi; Liu, Zhen; Xu, Guanghui; Liu, Shushang; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    Abstract Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis. Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center. The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs. The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs. PMID:26765432

  19. Treatment and long-term outcome of chronic radiation esophagitis after radiation therapy for head and neck tumors. A report of 13 cases.

    PubMed

    Silvain, C; Barrioz, T; Besson, I; Babin, P; Fontanel, J P; Daban, A; Matuchansky, C; Beauchant, M

    1993-05-01

    The natural history of chronic radiation esophagitis occurring in previously normal esophagus is still unknown. We describe here the long-term outcome of chronic esophagitis arising after neck irradiation for oropharynx and larynx carcinomas in 13 consecutive adult patients. The first clinical signs of radiation esophagitis were dysphagia or impossibility of oral intake, which appeared within 26 months (range 2-120 months) after the end of radiation for pyriform fossae carcinoma (N = 5), tonsil carcinoma (N = 2), larynx carcinoma (N = 2), pharynx carcinoma (N = 2), base of the tongue (N = 1), and thyroid carcinomas (N = 1). During upper endoscopy, an esophageal stenosis was found in 11 cases and was associated with ulceration in three cases. An isolated esophageal ulceration was present in only two cases. Chronic radiation esophagitis diagnosis was confirmed by histology and surgery in seven cases. In the last six cases, diagnosis was supported by the absence of first cancer relapses within a median follow-up of two years (16 months to nine years) and by endoscopic findings. Seven patients received parenteral or enteral nutrition. Ten patients were treated by peroral dilatations. These treatments allowed nearly normal oral diet in 11/13 patients. Only one patient was lost of follow-up after 20 months. Four patients died from chronic radiation esophagitis. One of these patients died from massive hemorrhage after peroral dilatation. Four patients died of a second carcinoma with no first cancer recurrence. Four patients were alive after six months to nine years of follow-up. Moderate dysphagia was still present, allowing nearly normal oral feeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8482193

  20. Relative permeability of retina and retinal pigment epithelium to the diffusion of tritiated water from vitreous to choroid

    SciTech Connect

    Orr, G.; Goodnight, R.; Lean, J.S.

    1986-11-01

    The movement of intravitreally injected tritiated water from the vitreous to the choroid was accelerated by the removal of intervening retina. Both rate of transfer and peak choroidal levels of the tracer were increased, but the proportion of the intravitreal dose recovered was unaltered. In contrast, the movement of tritiated water after diffuse damage to the retinal pigment epithelium by sodium iodate was similar to that of control eyes. The main resistance to the diffusion of this tracer from the vitreous to the choroid is the retina. The differential permeability of the retina and the retinal pigment epithelium may have a role in normal retinal adhesion.

  1. A striking local esophageal cytokine expression profile in eosinophilic esophagitis1

    PubMed Central

    Blanchard, Carine; Stucke, Emily M.; Rodriguez-Jimenez, Beatriz; Burwinkel, Karen; Collins, Margaret H.; Ahrens, Annette; Alexander, Eileen S.; Butz, Bridget K. Buckmeier; Jameson, Sean C.; Kaul, Ajay; Franciosi, James P.; Kushner, Jonathan P.; Putnam, Philip E.; Abonia, J. Pablo; Rothenberg, Marc E.

    2011-01-01

    Background Eosinophilic esophagitis (EE) is an emerging worldwide disease that mimics gastroesophageal reflux disease. Objective Early studies have suggested that esophageal eosinophilia occurs in association with T helper type 2 allergic responses, yet the local and systemic expression of relevant cytokines has not been well characterized. Methods A human inflammatory cytokine and receptor PCR array containing 84 genes followed by PCR validation and multiplex arrays were used to quantify cytokine mRNA in esophageal biopsies and blood levels. Results Esophageal transcripts of numerous chemokines [e.g. CCL1, CCL23, CCL26 (eotaxin-3), CXCL1, and CXCL2], cytokines (e.g. IL13 and ABCF1), and cytokine receptors (e.g. IL5RA) were induced at least 4-fold in individuals with EE. Analysis of esophageal biopsies (n=288) revealed that eotaxin-3 mRNA level alone had 89% sensitivity for distinguishing EE from non-EE individuals. The presence of allergy was associated with significantly increased esophageal expression of IL4 and IL5 mRNA in active EE patients. We identified 8 cytokines (IL-4, IL-13, IL-5, IL-6, IL-12p70, CD40L, IL-1?, and IL-17) whose blood levels retrospectively distinguished 12 non-EE from 13 EE patients with 100% specificity and 100% sensitivity. When applied to a blinded, prospectively recruited group of 36 patients, the cytokine panel scoring system had a 79% positive predictive value, 68% negative predictive value, 61% sensitivity, and 83% specificity for identifying EE. Conclusion Evidence is presented that IL13 and IL5 associate with eosinophil and eotaxin-3 levels, indicating the key role of adaptive Th2 immunity in regulating eotaxin-3-driven esophageal eosinophilia in the absence of a consistent systemic change in cytokines. PMID:21211656

  2. Esophageal perforation post pneumatic dilatation for achalasia managed by esophageal stenting

    PubMed Central

    Elhanafi, Sherif; Othman, Mohamed; Sunny, Joseph; Said, Sarmad; Cooper, Chad J.; Alkhateeb, Haider; Quansah, Raphael; McCallum, Richard

    2013-01-01

    Patient: Female, 82 Final Diagnosis: Achalasia Symptoms: Nocturnal regurgtation weight loss Medication: Clinical Procedure: Esophageal stenting Specialty: Gastroenterology Hepatology Objective: Unusual or unexpected effect of treatment Background: Pneumatic dilatation is one of the most effective methods for treating achalasia. Esophageal perforation is the most serious complication after pneumatic dilatation and has been reported to occur in the range of 1 to 4.3%. The appropriate management of esophageal perforation can range from conservative medical treatment to surgical intervention. Case Report: We report a case of an 82-year-old male who had an 8 month history of dysphagia for solid and liquids, a 10 lb weight loss and nocturnal regurgitation. The diagnosis of achalasia was established by endoscopic; barium and manometric criteria. He underwent a pneumatic dilation with a 30 mm Rigiflex balloon. A confined or limited esophageal perforation projecting into the mediastinum and located 12 cm above the diaphragm was confirmed by a gastrografin swallow study performed immediately after the procedure. There was some accompanying epigastric abdominal pain. Patient was treated later that day by placing a fully covered metallic esophageal stent in addition to antibiotics, proton pump inhibitor, and fasting. Patient was discharged home 3 days later able to eat liquid-soft foods. Follow up endoscopy 2 weeks later and a gastrografin swallow showed a completely healed perforation and the stent was removed. Symptomatically he has done well, with no dysphagia or heartburn at six and twelve months follow up. Conclusions: Early esophageal stenting for esophageal perforation after pneumatic dilation for achalasia is a treatment option which accelerates healing shortens recovery period, as well as decreasing hospital stay and costs. PMID:24349606

  3. Screening pre-bariatric surgery patients for esophageal disease with esophageal capsule endoscopy

    PubMed Central

    Shah, Ashish; Boettcher, Erica; Fahmy, Marianne; Savides, Thomas; Horgan, Santiago; Jacobsen, Garth R; Sandler, Bryan J; Sedrak, Michael; Kalmaz, Denise

    2013-01-01

    AIM: To determine if esophageal capsule endoscopy (ECE) is an adequate diagnostic alternative to esophagogastroduodenoscopy (EGD) in pre-bariatric surgery patients. METHODS: We conducted a prospective pilot study to assess the diagnostic accuracy of ECE (PillCam ESO2, Given Imaging) vs conventional EGD in pre-bariatric surgery patients. Patients who were scheduled for bariatric surgery and referred for pre-operative EGD were prospectively enrolled. All patients underwent ECE followed by standard EGD. Two experienced gastroenterologists blinded to the patients history and the findings of the EGD reviewed the ECE and documented their findings. The gold standard was the findings on EGD. RESULTS: Ten patients with an average body mass index of 50 kg/m2 were enrolled and completed the study. ECE identified 11 of 14 (79%) positive esophageal/gastroesophageal junction (GEJ) findings and 14 of 17 (82%) combined esophageal and gastric findings identified on EGD. Fishers exact test was used to compare the findings and no significant difference was found between ECE and EGD (P = 0.64 for esophageal/GEJ and P = 0.66 for combined esophageal and gastric findings respectively). Of the positive esophageal/GEJ findings, ECE failed to identify the following: hiatal hernia in two patients, mild esophagitis in two patients, and mild Schatzki ring in two patients. ECE was able to identify the entire esophagus in 100%, gastric cardia in 0%, gastric body in 100%, gastric antrum in 70%, pylorus in 60%, and duodenum in 0%. CONCLUSION: There were no significant differences in the likelihood of identifying a positive finding using ECE compared with EGD in preoperative evaluation of bariatric patients. PMID:24115815

  4. Barrier function of airway tract epithelium

    PubMed Central

    Ganesan, Shyamala; Comstock, Adam T; Sajjan, Uma S

    2013-01-01

    Airway epithelium contributes significantly to the barrier function of airway tract. Mucociliary escalator, intercellular apical junctional complexes which regulate paracellular permeability and antimicrobial peptides secreted by the airway epithelial cells are the three primary components of barrier function of airway tract. These three components act cooperatively to clear inhaled pathogens, allergens and particulate matter without inducing inflammation and maintain tissue homeostasis. Therefore impairment of one or more of these essential components of barrier function may increase susceptibility to infection and promote exaggerated and prolonged innate immune responses to environmental factors including allergens and pathogens resulting in chronic inflammation. Here we review the regulation of components of barrier function with respect to chronic airways diseases. PMID:24665407

  5. Effect of palonosetron (5HT-3 antagonist) and pantoprazole (proton pump inhibitor) against surgical esophagitis induced by forestomach and pylorus ligation in albino rats.

    PubMed

    Kumar, A; Gautam, S; Rawat, J K; Singh, M; Saraf, S A; Kaithwas, G

    2016-01-01

    This study was embarked upon to evaluate the effects of pantoprazole and palonosetron on experimental esophagitis in albino wistar rats. Groups of rats, fasted for 36 h, were subjected to pylorus and forestomach ligation, supervened by treatment with normal saline (3 ml/kg, po, sham control), esophagitis control (3 ml/kg, po), pantoprazole (30 mg/kg, po), palonosetron (0.5 mg/kg, po), and their combination. Animals were sacrificed after 12 h and appraised for the volume of gastric juices, total acidity, free acidity, and esophagitis index. Esophageal tissues were further figured out biochemically for markers of oxidative stress and inflammatory mediators. The combination therapy comparably inhibited the esophagitis index (52.86%), gastric volume (66.04%), free acidity (43.76%), and total acidity (42.60%) in comparison with toxic control. The combination therapy also subsidized the biochemical and inflammatory markers to the purview less than toxic control. The morphological changes were scrutinized by scanning electron microscopy and were observed to demonstrate momentous protection by the amalgamation therapy. Combination therapy with pantoprazole and palonosetron flaunted sententious protection against experimental esophagitis. PMID:25743726

  6. Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

    2014-02-01

    The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

  7. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    PubMed

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID:26877262

  8. The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium

    PubMed Central

    Grego-Bessa, Joaquim; Bloomekatz, Joshua; Castel, Pau; Omelchenko, Tatiana; Baselga, Jos; Anderson, Kathryn V

    2016-01-01

    Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.12034.001 PMID:26809587

  9. Remapping the body: learning to eat again after surgery for esophageal cancer.

    PubMed

    Wainwright, David; Donovan, Jenny L; Kavadas, Vas; Cramer, Helen; Blazeby, Jane M

    2007-07-01

    Surgery for esophageal cancer offers the hope of cure but might impair quality of life. The operation removes tumors obstructing the esophagus but frequently leaves patients with eating difficulties, leading to weight loss. Maintaining or increasing body weight is important to many patients, both as a means of returning to "normal" and as a means of rejecting the identity of the terminal cancer patient, but surgery radically alters embodied sensations of hunger, satiety, swallowing, taste, and smell, rendering the previously taken-for-granted experience of eating unfamiliar and alien. Successful recovery depends on patients' learning how to eat again. This entails familiarization with physiological changes but also coming to terms with the social consequences of spoiled identity. The authors report findings from in-depth interviews with 11 esophageal cancer patients, documenting their experiences as they struggle to achieve a process of adaptation that is at once physiological, psychological, and social. PMID:17582019

  10. High-activity intraluminal 192iridium endocurietherapy for treatment of esophageal cancer.

    PubMed

    Kumar, P P; Good, R R

    1986-01-01

    Intraluminal endocurietherapy (ECT) with high-activity 192Iridium administered via catheter following megavoltage external-beam radiotherapy, allows delivery of 8,000-10,000 rad to the target volume without exceeding the normal tissue radiation tolerances of surrounding vital structures. The endocurietherapy does not require surgery, general or local anesthesia. The technique is accurate, cost-effective, and allows safe delivery of higher radiation doses than could be tolerated by multiple-field external-beam megavoltage radiotherapy techniques alone. In a pilot Phase-1 toxicity study of six patients treated with minimum tumor doses of 8,000 rad, the majority of patients developed benign esophageal stricture 2-6 months following ECT which was managed by dilatation or gastrostomy. No patients developed esophageal perforation. Local tumor control was excellent, but a high proportion of patients developed distant metastatic disease. PMID:3099341

  11. 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.

  12. Invasive bacterial pathogens exploit TLR-mediated downregulation of tight junction components to facilitate translocation across the epithelium.

    PubMed

    Clarke, Thomas B; Francella, Nicholas; Huegel, Alyssa; Weiser, Jeffrey N

    2011-05-19

    Streptococcus pneumoniae and Haemophilus influenzae are members of the normal human nasal microbiota with the ability to cause invasive infections. Bacterial invasion requires translocation across the epithelium; however, mechanistic understanding of this process is limited. Examining the epithelial response to murine colonization by S. pneumoniae and H. influenzae, we observed the TLR-dependent downregulation of claudins 7 and 10, tight junction components key to the maintenance of epithelial barrier integrity. When modeled in vitro, claudin downregulation was preceded by upregulation of SNAIL1, a transcriptional repressor of tight junction components, and these phenomena required p38 MAPK and TGF-? signaling. Consequently, downregulation of SNAIL1 expression inhibited bacterial translocation across the epithelium. Furthermore, disruption of epithelial barrier integrity by claudin 7 inhibition in vitro or TLR stimulation in vivo promoted bacterial translocation. These data support a general mechanism for epithelial opening exploited by invasive pathogens to facilitate movement across the epithelium to initiate disease. PMID:21575911

  13. Esophageal leiomyoma: experience from a single institution.

    PubMed

    Jiang, W; Rice, T W; Goldblum, J R

    2013-01-01

    Esophageal leiomyomas are rare. We report the clinicopathologic features of one of the largest series of esophageal leiomyomas from a single institution. We retrospectively reviewed the Cleveland Clinic pathology database (1985-2010) for patients with a diagnosis of esophageal leiomyoma(s). Clinicopathologic features of 30 cases from 28 patients were analyzed. The group included 15 females and 13 males with a mean age at diagnosis of 56 years. These include 9 excisions, 9 esophagectomies, and 12 endoscopic biopsies. Only one partial esophagectomy was performed solely for a symptomatic 14-cm leiomyoma; the remainder of the resections (n= 8) were for other indications, including esophageal cancer (Barrett's esophagus-related adenocarcinoma and squamous cell carcinoma) and emergent esophageal perforation, with leiomyoma being an incidental finding. One patient (2.5%) had two synchronous leiomyomas (14 cm and 0.3 cm). Tumor size ranged from 0.1 to 14 cm (mean = 2.0 cm). Mean tumor size among symptomatic patients was 5.2 cm, as compared with 0.4 cm in asymptomatic patients. Dysphagia was the most common complaint in symptomatic patients (71.4%). Sixty-nine percent of the tumors were located in the distal and middle thirds of the esophagus, with most (69.6%) arising from muscularis propria. Histologically, these tumors were composed of bland spindle cells with low cellularity, no nuclear atypia, or mitotic activity. Only one case (14 cm) showed focal moderate cellularity and nuclear atypia, with low mitotic activity (<1/10 high power field). Immunohistochemical studies showed tumor cells were positive for smooth muscle actin, and negative for CD34 and CD117. Follow-up information was available for 22 patients (78.6%), and none had adverse events related to leiomyoma. In summary, esophageal leiomyoma is a rare benign tumor of the esophagus. Patients with larger tumors were more likely to have symptoms. The majority of the tumors were in the lower and mid-esophagus, and arose from muscularis propria. These tumors behave in a clinically benign fashion. PMID:22458777

  14. Endoscopic palliation of advanced esophageal cancer

    PubMed Central

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

    2015-01-01

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

  15. Surgical treatment analysis of idiopathic esophageal achalasia

    PubMed Central

    de AQUINO, José Luis Braga; SAID, Marcelo Manzano; PEREIRA, Douglas Rizzanti; do AMARAL, Paula Casals; LIMA, Juliana Carolina Alves; LEANDRO-MERHI, Vânia Aparecida

    2015-01-01

    Background Idiopathic esophageal achalasia is an inflammatory disease of unknown origin, characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter in response to swallowing, with consequent dysphagia. Aim To demonstrate the results of surgical therapy in these patients, evaluating the occurred local and systemic complications. Methods Were studied retrospectively 32 patients, 22 of whom presented non-advanced stage of the disease (Stage I/II) and 10 with advanced disease (Stage III/IV). All of them had the clinical conditions to be submitted to surgery. The diagnoses were done by clinical, endoscopic, cardiological, radiological and esophageal manometry analysis. Pre-surgical evaluation was done with a questionnaire based on the most predisposing factors in the development of the disease and the surgical indication was based on the stage of the disease. Results The patients with non-advanced stages were submitted to cardiomyotomy with fundoplication, wherein in the post-surgical early assessment, only one (4,4%) presented pulmonary infection, but had a good outcome. In patients with advanced disease, seven were submitted to esophageal mucosectomy preserving the muscular layer, wherein one patient (14,2%) presented dehiscence of gastric cervical esophagus anastomosis as well as pulmonary infection; all of these complications were resolved with proper specific treatment; the other three patients with advanced stage were submitted to transmediastinal esophagectomy; two of them presented hydropneumothorax with good evolution, and one of them also presented fistula of the cervical esophagogastric anastomosis, but with spontaneous healing after conservative treatment and nutritional support. The two patients with fistula of the cervical anastomosis progressed to stenosis, with good results after endoscopic dilations. In the medium and long term assessment done in 23 patients, all of them reported improvement in life quality, with return to swallowing. Conclusion The strategy proposed for the surgical treatment of idiopathic esophageal achalasia according to the stages of the disease was of great value, due to post-surgical low morbidity complications and proper recovery of swallowing. PMID:26176243

  16. 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

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

    PubMed

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

    2011-07-01

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

  18. Follow-up barium study after a negative water-soluble contrast examination for suspected esophageal leak: is it necessary?

    PubMed

    Sanchez, Thomas R; Holz, Grant S; Corwin, Michael T; Wood, Robert J; Wootton-Gorges, Sandra L

    2015-10-01

    The purpose of this study was to determine the value of follow-up barium esophogram in diagnosing esophageal injury or leak if the initial water-soluble contrast examination of the esophagus is normal. An institutional review board (IRB)-approved retrospective review of all pediatric patients less than 18years old referred to the radiology department for evaluation of esophageal injury or leak was performed for a 9-year period from 2005 to 2014. The majority of patients had unexplained pneumomediastinum, chest trauma (gunshot or puncture wound), or foreign body ingestion as the reason for the referral. Forty-nine patients (age range 10days to 17years) underwent an initial water-soluble esophogram immediately followed by a barium esophogram. Forty-six studies were negative on both water-soluble contrast and barium studies. Two studies were both positive on the initial water-soluble contrast and subsequent barium studies. A single study showed the esophageal leak only in the water-soluble study, with the follow-up barium exam being normal. The result of this study indicates that a single-contrast water-soluble esophogram alone is sensitive in the diagnosis of esophageal injury or leak. It has a 100% sensitivity and negative predictive value. A follow-up barium esophogram only increases the study time and radiation dose to the patient. PMID:26076944

  19. 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

  20. 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

  1. Cigarette smoke mediates epigenetic repression of miR-217 during esophageal adenocarcinogenesis.

    PubMed

    Xi, S; Inchauste, S; Guo, H; Shan, J; Xiao, Z; Xu, H; Miettenen, M; Zhang, M R; Hong, J A; Raiji, M T; Altorki, N K; Casson, A G; Beer, D G; Robles, A I; Bowman, E D; Harris, C C; Steinberg, S M; Schrump, D S

    2015-10-29

    Although microRNAs (miRs) have been implicated in the pathogenesis of various human malignancies, limited information is available regarding mechanisms by which these noncoding RNAs contribute to initiation and progression of tobacco-induced esophageal cancers. In this study, array and quantitative reverse transcriptase-PCR techniques were used to examine miR expression in immortalized esophageal epithelia (IEE) and esophageal adenocarcinoma (EAC) cells cultured in normal media with or without cigarette smoke condensate (CSC). Under relevant exposure conditions, CSC significantly decreased miR-217 expression in these cells. Endogenous levels of miR-217 expression in cultured EAC cells (EACC)/primary EACs were significantly lower than those observed in IEE/ paired normal esophageal tissues. RNA crosslink immunoprecipitation, quantitative reverse transcriptase-PCR (qRT-PCR) and immunoblot experiments demonstrated direct interaction of miR-217 with kallikrein 7 (KLK7), encoding a putative oncogene not previously implicated in EAC. Repression of miR-217 correlated with increased levels of KLK7 in primary EACs, particularly those from smokers. Chromatin and methylated DNA immunoprecipitation experiments demonstrated that CSC-mediated repression of miR-217 coincided with DNMT3b-dependent hypermethylation and decreased occupancy of nuclear factor 1 within the miR-217 genomic locus. Deoxyazacytidine induced miR-217 expression and downregulated KLK7 in EACC; deoxyazacytidine also attenuated CSC-mediated miR-217 repression and upregulation of KLK7 in IEE and EACC. Overexpression of miR-217 significantly decreased, whereas overexpression of KLK7 increased proliferation, invasion and tumorigenicity of EACC. Collectively, these data demonstrate that epigenetic repression of miR-217 contributes to the pathogenesis of EAC via upregulation of KLK7 and suggest that restoration of miR-217 expression may be a novel treatment strategy for these malignancies. PMID:25703328

  2. Ascl1 (Mash1) Knockout Perturbs Differentiation of Nonneuronal Cells in Olfactory Epithelium

    PubMed Central

    Jang, Woochan; Wildner, Hendrik; Schwob, James E.

    2012-01-01

    The embryonic olfactory epithelium (OE) generates only a very few olfactory sensory neurons when the basic helix-loop-helix transcription factor, ASCL1 (previously known as MASH1) is eliminated by gene mutation. We have closely examined the structure and composition of the OE of knockout mice and found that the absence of neurons dramatically affects the differentiation of multiple other epithelial cell types as well. The most prominent effect is observed within the two known populations of stem and progenitor cells of the epithelium. The emergence of horizontal basal cells, a multipotent progenitor population in the adult epithelium, is anomalous in the Ascl1 knockout mice. The differentiation of globose basal cells, another multipotent progenitor population in the adult OE, is also aberrant. All of the persisting globose basal cells are marked by SOX2 expression, suggesting a prominent role for SOX2 in progenitors upstream of Ascl1. However, NOTCH1-expressing basal cells are absent from the knockout; since NOTCH1 signaling normally acts to suppress Ascl1 via HES1 and drives sustentacular (Sus) cell differentiation during adult epithelial regeneration, its absence suggests reciprocity between neurogenesis and the differentiation of Sus cells. Indeed, the Sus cells of the mutant mice express a markedly lower level of HES1, strengthening that notion of reciprocity. Duct/gland development appears normal. Finally, the expression of cKIT by basal cells is also undetectable, except in those small patches where neurogenesis escapes the effects of Ascl1 knockout and neurons are born. Thus, persistent neurogenic failure distorts the differentiation of multiple other cell types in the olfactory epithelium. PMID:23284756

  3. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    PubMed Central

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the conventional treatment. PMID:25478446

  4. Innovative techniques in evaluating the esophagus; imaging of esophageal morphology and function; and drugs for esophageal disease.

    PubMed

    Neumann, Helmut; Neurath, Markus F; Vieth, Michael; Lever, Frederiek M; Meijer, Gert J; Lips, Irene M; McMahon, Barry P; Ruurda, J P; van Hillegersberg, R; Siersema, P; Levine, Marc S; Scharitzer, Martina; Pokieser, Peter; Zerbib, Frank; Savarino, Vincenzo; Zentilin, Patrizia; Savarino, Edoardo; Chan, Walter W

    2013-10-01

    This paper reporting on techniques for esophageal evaluation and imaging and drugs for esophageal disease includes commentaries on endoscopy techniques including dye-based high-resolution and dye-less high-definition endoscopy; the shift from CT to MRI guidance in tumor delineation for radiation therapy; the role of functional lumen imaging in measuring esophageal distensibility; electrical stimulation of the lower esophageal sphincter (LES) as an alternative to fundoduplication for treatment of gastroesophageal reflux disease (GERD); the morphological findings of reflux esophagitis and esophageal dysmotility on double-contrast esophagography; the value of videofluoroscopy in assessing protecting mechanisms in patients with chronic reflux or swallowing disorders; targeting visceral hypersensitivity in the treatment of refractory GERD; and the symptoms and treatments of nighttime reflux and nocturnal acid breakthrough (NAB). PMID:24117631

  5. A Case of Esophageal Squamous Cell Carcinoma with Pancreatic Metastasis

    PubMed Central

    Park, Choulki; Kim, Youn Hwa; Hwang, Eun Jung; Na, Ki Yong; Kim, Kyung-Yup; Park, Jae Hyun; Chang, Young Woon

    2013-01-01

    Solitary pancreatic metastasis of esophageal cancer is extremely rare. We report the case of a 58-year-old male admitted with esophageal cancer. Additional asymptomatic solitary hepatic and pancreatic masses were observed in the staging work-up for esophageal cancer. The hepatic mass was confirmed as a primary hepatocellular carcinoma with an ultrasound-guided needle biopsy. An esophagectomy with a distal pancreatectomy and radiofrequency ablation for hepatocellular carcinoma were performed. Histologically, the pancreatic mass was confirmed to be a metastasis from the esophageal cancer. The patient has been followed up with chemotherapy. PMID:23614134

  6. Aortic Pseudoaneurysm Secondary to Mediastinitis due to Esophageal Perforation

    PubMed Central

    Zuluaga, Claudia Patricia; Aluja Jaramillo, Felipe; Velásquez Castaño, Sergio Andrés; Rivera Bernal, Aura Lucía; Granada, Julio Cesar; Carrillo Bayona, Jorge Alberto

    2016-01-01

    Esophageal perforation is a condition associated with high morbidity and mortality rates; it requires early diagnosis and treatment. The most common complication of esophageal rupture is mediastinitis. There are several case reports in the literature of mediastinitis secondary to esophageal perforation and development of aortic pseudoaneurysm as a complication. We report the case of a patient with an 8-day history of esophageal perforation due to foreign body (fishbone) with mediastinitis and aortic pseudoaneurysm. The diagnosis was made using Computed Tomography (CT) with intravenous and oral water-soluble contrast material. An esophagogastroduodenoscopy did not detect the perforation. PMID:26977330

  7. Esophageal cancer: Recent advances in screening, targeted therapy, and management

    PubMed Central

    Gaur, Puja; Kim, Min P.; Dunkin, Brian J.

    2014-01-01

    The incidence of esophageal cancer remains on the rise worldwide and despite aggressive research in the field of gastrointestinal oncology, the survival remains poor. Much remains to be defined in esophageal cancer, including the development of an effective screening tool, identifying a good tumor marker for surveillance purposes, ways to target esophageal cancer stem cells as well as circulating tumor cells, and developing minimally invasive protocols to treat early-stage disease. The goal of this chapter is to highlight some of the recent advances and ongoing research in the field of esophageal cancer. PMID:25395880

  8. Microbiome, innate Immunity, and esophageal adenocarcinoma

    PubMed Central

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

    2014-01-01

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

  9. GWAS identifies four novel eosinophilic esophagitis loci

    PubMed Central

    Sleiman, Patrick MA; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J.; Furuta, Glenn T.; Spergel, Jonathan M.; Hakonarson, Hakon

    2014-01-01

    Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the esophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune disease, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the esophagus. The identification of five EoE loci, not only expands our etiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, esophageal inflammation and remodeling. PMID:25407941

  10. 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

  11. Lysosomes: Regulators of autophagy in the retinal pigmented epithelium.

    PubMed

    Sinha, Debasish; Valapala, Mallika; Shang, Peng; Hose, Stacey; Grebe, Rhonda; Lutty, Gerard A; Zigler, J Samuel; Kaarniranta, Kai; Handa, James T

    2016-03-01

    The retinal pigmented epithelium (RPE) is critically important to retinal homeostasis, in part due to its very active processes of phagocytosis and autophagy. Both of these processes depend upon the normal functioning of lysosomes, organelles which must fuse with (auto)phagosomes to deliver the hydrolases that effect degradation of cargo. It has become clear that signaling through mTOR complex 1 (mTORC1), is very important in the regulation of lysosomal function. This signaling pathway is becoming a target for therapeutic intervention in diseases, including age-related macular degeneration (AMD), where lysosomal function is defective. In addition, our laboratory has been studying animal models in which the gene (Cryba1) for ?A3/A1-crystallin is deficient. These animals exhibit impaired lysosomal clearance in the RPE and pathological signs that are similar to some of those seen in AMD patients. The data demonstrate that ?A3/A1-crystallin localizes to lysosomes in the RPE and that it is a binding partner of V-ATPase, the proton pump that acidifies the lysosomal lumen. This suggests that ?A3/A1-crystallin may also be a potential target for therapeutic intervention in AMD. In this review, we focus on effector molecules that impact the lysosomal-autophagic pathway in RPE cells. PMID:26321509

  12. Surface characteristics of isopod digestive gland epithelium studied by SEM.

    PubMed

    Millaku, Agron; Leser, Vladka; Drobne, Damjana; Godec, Matjaz; Torkar, Matjaz; Jenko, Monika; Milani, Marziale; Tatti, Francesco

    2010-05-01

    The structure of the digestive gland epithelium of a terrestrial isopod Porcellio scaber has been investigated by conventional scanning electron microscopy (SEM), focused ion beam-scanning electron microscopy (FIB/SEM), and light microscopy in order to provide evidence on morphology of the gland epithelial surface in animals from a stock culture. We investigated the shape of cells, extrusion of lipid droplets, shape and distribution of microvilli, and the presence of bacteria on the cell surface. A total of 22 animals were investigated and we found some variability in the appearance of the gland epithelial surface. Seventeen of the animals had dome-shaped digestive gland "normal" epithelial cells, which were densely and homogeneously covered by microvilli and varying proportions of which extruded lipid droplets. On the surface of microvilli we routinely observed sparsely distributed bacteria of different shapes. Five of the 22 animals had "abnormal" epithelial cells with a significantly altered shape. In three of these animals, the cells were much smaller, partly or completely flat or sometimes pyramid-like. A thick layer of bacteria was detected on the microvillous border, and in places, the shape and size of microvilli were altered. In two animals, hypertrophic cells containing large vacuoles were observed indicating a characteristic intracellular infection. The potential of SEM in morphological investigations of epithelial surfaces is discussed. PMID:20155290

  13. Significance of feeding dysfunction in eosinophilic esophagitis

    PubMed Central

    Menard-Katcher, Calies; Henry, Michelle; Furuta, Glenn T; Atkins, Dan; Maune, Nancy Creskoff; Haas, Angela M

    2014-01-01

    Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis (EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth. PMID:25152606

  14. Endoscopic management of impacted esophageal foreign bodies.

    PubMed

    Chen, T; Wu, H-F; Shi, Q; Zhou, P-H; Chen, S-Y; Xu, M-D; Zhong, Y-S; Yao, L-Q

    2013-01-01

    There are many reports on the endoscopic management of ingested foreign bodies in the upper gastrointestinal tract, however, little is known about the management of a specific subset of esophageal foreign bodies - impacted esophageal foreign bodies (IEFBs), especially perforating esophageal foreign bodies (PEFBs). The aim of this retrospective study on 78 cases was to report experience and outcome in the endoscopic management of the IEFBs in Chinese patients. From January 2006 to July 2011, a total of 750 patients with suspected upper gastrointestinal foreign bodies were admitted to the endoscopy center. Among these 750 patients, 78 cases that met the defined criteria of IEFBs were retrospectively enrolled in the present study, including 12 cases (12/78, 15.4%) with PEFBs. The major types of IEFBs were poultry bones (35.9%) and fish bones (17.9%). Most of the IEFBs (80.8%) were located in the upper esophagus, as were two thirds (66.7%) of the PEFBs. Foreign-body retrieval forceps were the most frequently used accessory devices. Extraction of IEFBs failed in eight patients (10.3%) during the endoscopic procedure. The difficult points in endoscopic management were PEFBs, IEFBs with sharp points, and those with impaction for more than 24 hours. IEFBs should be treated as early as possible, and their endoscopic management is safe and effective. Endoscopic management is the first choice for PEFBs when the duration of impaction is less than 24 hours and there are no abscesses outside of the esophageal tract as determined by a computed tomography scan. PMID:22973974

  15. Significance of feeding dysfunction in eosinophilic esophagitis.

    PubMed

    Menard-Katcher, Calies; Henry, Michelle; Furuta, Glenn T; Atkins, Dan; Maune, Nancy Creskoff; Haas, Angela M

    2014-08-21

    Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis (EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth. PMID:25152606

  16. Advances in Clinical Management of Eosinophilic Esophagitis

    PubMed Central

    Dellon, Evan S.; Liacouras, Chris A.

    2014-01-01

    EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines—EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885

  17. Eosinophilic Esophagitis: update on treatment approaches

    PubMed Central

    Fotis, L; Xatzipsalti, M; Papadopoulou, A

    2012-01-01

    ?osinophilic esophagitis (EoE) is a clinical entity with continuously increasing incidence in children and adults. Diet therapy and corticosteroids are the most important therapeutic interventions currently used, while new therapies are being developed, based on the research of the disease mechanisms. In this review we assess the results of the latest clinical trials on management of patients with EoE, and the advances in the development of novel drug therapies. Hippokratia 2012; 16 (3): 200-204 PMID:23935283

  18. VEGF Modulation of Retinal Pigment Epithelium Resistance

    PubMed Central

    Ablonczy, Zsolt; Crosson, Craig E.

    2008-01-01

    Fluid accumulation into the subretinal space and the development of macular edema is a common condition in age-related macular degeneration, diabetic retinopathy, and following ocular surgery, or injury. Vascular endothelial growth factor (VEGF) and other cytokines have been implicated in the disruption of retinal pigment epithelium (RPE) barrier function and a reduction in the regulated removal of subretinal fluid; however, the cellular and molecular events linking these agents to the disruption of barrier function have not been established. In the current study, cultures of ARPE-19 and primary porcine retinal pigment epithelium (RPE) cells were utilized to investigate the effects of the VEGF-induced modifications to the barrier properties of the RPE. The barrier function was determined by transepithelial resistance (TER) measurements and morphology of the RPE monolayers. In both ARPE-19 and primary porcine RPE cells the administration of VEGF produced a significant drop in TER, and this response was only observed following apical administration. Maximum reduction in TER was reached 5 hours post VEGF administration. These responses were concentration-dependent with an EC50 of 502 pg/mL in ARPE-19 cells and 251 pg/mL in primary porcine cells. In both ARPE-19 and primary RPE cells, the response to VEGF was blocked by pretreatment with the relatively selective VEGF-R2 antagonists, SU5416 or ZM323881, or the protein tyrosine kinase inhibitor, genistein. Administration of the relatively selective VEGF-R2 agonist, VEGF-E, also reduced TER in a concentration-dependent manner (EC50 of 474 pg/mL), while VEGF-R1 agonist, placental growth factor (PlGF), did not significantly alter the TER. Immunolocalization studies demonstrated that confluent monolayers exhibited continuous cell-to-cell ZO-1 protein contacts and apical localization of the VEGF-R2 receptors. These data provide evidence that the VEGF-induced breakdown of RPE barrier function is mediated by the activation of apically-oriented VEGF-R2 receptors. Thus, VEGF-mediated increases in RPE permeability are initiated by a rise in intraocular levels of VEGF. PMID:17915218

  19. Ultrastructural study on the plical epithelium of the bursa of Fabricius in chick embryos: influence of partial decerebration and hypophyseal allografts.

    PubMed Central

    Romano, N; Baldassini, M R; Abelli, L; Aita, M; Mastrolia, L

    1996-01-01

    The bursa of Fabricius of 18 day normal and partially decerebrated chick embryos, and partially decerebrated embryos bearing a hypophyseal allograft was analysed by scanning and transmission electron microscopy, focusing on the ultrastructural characterisation of the plical epithelium. The plicae of the normal bursa consist of interfollicular (IFE) and follicle associated epithelium (FAE). The FAE is composed of typical polygonal cells and is supported by a layer of epithelial cells which appears as a continuation of the corticomedullary epithelium. Bordering cells lie between the FAE and IFE. The IFE is composed of 4 cell types: (1) undifferentiated, (2) goblet, at various stages of maturity, (3) prismatic, and (4) globular light cells. Partially decerebrated embryos showed a gross impairment of plical epithelium development and the complex of FAE and IFE cells was largely undifferentiated. Partially decerebrated embryos with a hypophyseal allograft displayed the same cellular types as observed in controls, thus indicating a restored differentiation of plical epithelium. These findings suggest that the hypophysis affects the differentiation of plical epithelium during ontogenesis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Figs 8-11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 PMID:8655413

  20. Lidocaine inhibition of esophageal peristalsis and lower esophageal sphincter pressure in baboons.

    PubMed

    Sinar, D R; Carey, L C; Cordova, C; Fletcher, J R; Castell, D O

    1985-11-01

    Intravenous lidocaine was infused at 0.82 ml/min in a concentration of 1.2 mg/ml (2.3 mg/kg) for 120 min in awake chair-restrained baboons (Papio anubis), and measurements of esophageal peristalsis and LES pressure were compared before and after lidocaine or control infusions. Lidocaine produced a progressive and significant (P less than 0.05) decrease in amplitude in the peristaltic wave in the smooth muscle portion of the distal esophagus during the 120-min infusion. Lower esophageal sphincter pressure was similarly significantly lower than control after the infusion of lidocaine (P less than 0.05). Velocity and duration of the peristaltic wave were unchanged during the infusion. The decreased amplitude occurred during therapeutic and stable serum concentrations of lidocaine. It did not appear that the inhibitory effect of lidocaine was due to an induction of prostaglandin synthesis, because pretreatment of animals with indomethacin did not change the inhibitory effect of lidocaine, and serum metabolites of prostacyclin decreased during the infusion. Furthermore, the inhibitory effect of lidocaine was not topical. The response to the muscarinic agonist, bethanechol was similar in lidocaine-treated animals and control animals. The preservation of a bethanechol response after lidocaine inhibition of LES pressure and distal esophageal amplitude suggests that lidocaine acts proximal to the muscarinic receptor in the esophageal body and smooth muscle portion of the lower esophageal sphincter. This study suggests that lidocaine produces an inhibitory effect on the peristaltic wave and lower esophageal sphincter pressure that is similar to inhibitory effects described after anticholinergic agents and calcium channel blocking drugs, but intravenous lidocaine infusion requires a longer period of time to produce inhibition of muscle function. PMID:2865090

  1. The neural regulation of the mammalian esophageal motility and its implication for esophageal diseases.

    PubMed

    Shiina, Takahiko; Shima, Takeshi; Wrl, Jrgen; Neuhuber, Winfried L; Shimizu, Yasutake

    2010-04-01

    In contrast to the tunica muscularis of the stomach, small intestine and large intestine, the external muscle layer of the mammalian esophagus contains not only smooth muscle but also striated muscle fibers. Although the swallowing pattern generator initiates the peristaltic movement via vagal preganglionic neurons that project to the myenteric ganglia in the smooth muscle esophagus, the progressing front of contraction is organized by a local reflex circuit composed by intrinsic neurons similarly to other gastrointestinal tracts. On the other hand, the peristalsis of the striated muscle esophagus is both initiated and organized by the swallowing pattern generator via vagal motor neurons that directly innervate the muscle fibers. The presence of a distinct ganglionated myenteric plexus in the striated muscle portion of the esophagus had been enigmatic and neglected in terms of peristaltic control for a long time. Recently, the regulatory roles of intrinsic neurons in the esophageal striated muscle have been clarified. It was reported that esophageal striated muscle receives dual innervation from both vagal motor fibers originating in the brainstem and varicose intrinsic nerve fibers originating in the myenteric plexus, which is called 'enteric co-innervation' of esophageal motor endplates. Moreover, a putative local neural reflex pathway that can control the motility of the striated muscle was identified in the rodent esophagus. This reflex circuit consists of primary afferent neurons and myenteric neurons, which can modulate the release of neurotransmitters from vagal motor neurons in the striated muscle esophagus. The pathogenesis of some esophageal disorders such as achalasia and gastroesophageal reflux disease might be involved in dysfunction of the neural networks including alterations of the myenteric neurons. These evidences indicate the physiological and pathological significance of intrinsic nervous system in the regulation of the esophageal motility. In addition, it is assumed that the components of intrinsic neurons might be therapeutic targets for several esophageal diseases. PMID:19497713

  2. 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

  3. Endoscopic resection of gastric and esophageal cancer.

    PubMed

    Balmadrid, Bryan; Hwang, Joo Ha

    2015-11-01

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

  4. Endoscopic resection of gastric and esophageal cancer

    PubMed Central

    Balmadrid, Bryan; Hwang, Joo Ha

    2015-01-01

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

  5. Current advances in esophageal cancer proteomics.

    PubMed

    Uemura, Norihisa; Kondo, Tadashi

    2015-06-01

    We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics. PMID:25233958

  6. Esophageal Dose Tolerance to Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors for Late Toxicity

    SciTech Connect

    Stephans, Kevin L.; Djemil, Toufik; Diaconu, Claudiu; Reddy, Chandana A.; Xia, Ping; Woody, Neil M.; Greskovich, John; Makkar, Vinit; Videtic, Gregory M.M.

    2014-09-01

    Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). Methods and Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. Results: The median esophageal point dose and 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Conclusions: Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy should be considered when delivering SBRT near the esophagus.

  7. Comparison of hepatic venous pressure gradient and endoscopic grading of esophageal varices

    PubMed Central

    Lee, EunJi; Kim, Yong Jae; Goo, Dong Erk; Yang, Seung Boo; Kim, Hyun-Joo; Jang, Jae Young; Jeong, Soung Won

    2016-01-01

    AIM: To determine the correlation between the hepatic venous pressure gradient and the endoscopic grade of esophageal varices. METHODS: From September 2009 to March 2013, a total of 176 measurements of hepatic venous pressure gradient (HVPG) were done in 146 patients. Each transjugular HVPG was measured twice, first using an end whole catheter (EH-HVPG), and then using a balloon catheter (B-HVPG). The HVPG was compared with the endoscopic grade of esophageal varices (according to the general rules for recording endoscopic findings of esophagogastric varices), which was recorded within a month of the measurement of HVPG. RESULTS: The study included 110 men and 36 women, with a mean age of 56.1 years (range, 43-76 years). The technical success rate of the pressure measurements was 100% and there were no complication related to the procedures. Mean HVPG was 15.3 mmHg as measured using the end hole catheter method and 16.5 mmHg as measured using the balloon catheter method. Mean HVPG (both EH-HVPG and B-HVPG) was not significantly different among patients with different characteristics, including sex and comorbid factors, except for cases with hepatocellular carcinoma (B-HVPG, P = 0.01; EH-HVPG, P = 0.02). Portal hypertension (> 12 mmHg HVPG) occurred in 66% of patients according to EH-HVPG and 83% of patients according to B-HVGP, and significantly correlated with Child’s status (B-HVPG, P < 0.000; EH-HVGP, P < 0.000) and esophageal varies observed upon endoscopy (EH-HVGP, P = 0.003; B-HVGP, P = 0.006). One hundred and thirty-five endoscopies were performed, of which 15 showed normal findings, 27 showed grade 1 endoscopic esophageal varices, 49 showed grade 2 varices, and 44 showed grade 3 varices. When comparing endoscopic esophageal variceal grades and HVPG using univariate analysis, the P value was 0.004 for EH-HVPG and 0.002 for B-HVPG. CONCLUSION: Both EH-HVPG and B-HVPG showed a positive correlation with the endoscopic grade of esophageal varices, with B-HVPG showing a stronger correlation than EH-HVPG. PMID:27003998

  8. Esophageal eosinophilia is increased in rural areas with low population density: Results from a national pathology database

    PubMed Central

    Jensen, Elizabeth T.; Hoffman, Kate; Shaheen, Nicholas J.; Genta, Robert M.; Dellon, Evan S.

    2015-01-01

    Objectives Eosinophilic esophagitis (EoE) is an increasingly prevalent chronic disease arising from an allergy/immune-mediated process. Generally, the risk of atopic disease differs in rural and urban environments. The relationship between population density and EoE is unknown. Our aim was to assess the relationship between EoE and population density. Methods : We conducted a cross-sectional, case-control study of patients with esophageal biopsies in a U.S. national pathology database between January 2009 and June 2012 to assess the relationship between population density and EoE. Using Geographic Information Systems (GIS), the population density (individuals/mile2) was determined for each patient zip code. The odds of esophageal eosinophilia and EoE were estimated for each quintile of population density and adjusted for potential confounders. Sensitivity analyses were conducted with varying case definitions and to evaluate the potential for bias from endoscopy volume and patient factors. Results Of 292,621 unique patients in the source population, 89,754 had normal esophageal biopsies and 14,381 had esophageal eosinophilia with ?15 eosinophils per high-power field (eos/hpf). The odds of esophageal eosinophilia increased with decreasing population density (p for trend < 0.001). Compared to those in the highest quintile of population density, odds of esophageal eosinophilia were significantly higher amongst those in the lowest quintile of population density (aOR 1.27, 95% CI: 1.18, 1.36). A similar dose-response trend was observed across case definitions with odds of EoE increased in the lowest population density quintile (aOR 1.59, 95% CI: 1.45-1.76). Estimates were robust to sensitivity analyses. Conclusions Population density is strongly and inversely associated with esophageal eosinophilia and EoE. This association is robust to varying case definitions and adjustment factors. Environmental exposures more prominent in rural areas may be relevant to the pathogenesis of EoE. PMID:24667575

  9. Changes in the Adult Vertebrate Auditory Sensory Epithelium After Trauma

    PubMed Central

    Oesterle, Elizabeth C.

    2012-01-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes. PMID:23178236

  10. Breast cancer resistance protein (BCRP) and excision repair cross complement-1 (ERCC1) expression in esophageal cancers and response to cisplatin and irinotecan based chemotherapy

    PubMed Central

    Bharthuar, Anubha; Black, Jennifer D.; Levea, Charles; Malhotra, Usha; Mashtare, Terry L.; Iyer, Renuka

    2014-01-01

    Background Esophageal cancer patients face a dismal outcome despite tri-modality management and median survival remains 15-18 months. Breast cancer resistance protein (BCRP) is an ATP-dependent efflux protein associated with chemotherapy resistance. The role of BCRP expression in esophageal cancer and normal esophageal cells is not known. Excision repair cross complement-1 (ERCC1) overexpression has been correlated with poorer response to cisplatin based chemotherapy. We examined the expression of BCRP and ERCC1 in patients with esophageal cancer and correlated it with survival in patients receiving irinotecan and cisplatin based chemotherapy. Methods With IRB approval, 40 cases of esophageal cancer diagnosed from 2004-2008, were stained for BCRP and ERCC1 expression by immunohistochemistry and scored by a pathologist blinded to clinical data. Baseline demographics, therapy given and survival data were collected and correlated with BCRP and ERCC1 expression. Fishers exact test was used to determine association between BCRP and ERCC1 expression and demographics. Cox proportional hazards model was used for association of BCRP and ERCC1 with survival. Results On immunohistochemistry, 30/40 cancers (75%) expressed BCRP. Interestingly, down-regulation of BCRP expression in tumor compared with normal cells was seen in 40% of patients. ERCC1 positivity was seen in 15/30 cases (50%). Median overall survival (OS) was 19 months with no difference in survival between BCRP positive and negative patients (P=0.13) or ERCC1 positive and negative patients (P=0.85). Estimated hazard ratio (HR) of death for BRCP positive patients was 2.29 (95% CI: 0.79-6.64) and for ERCC1 positive patients was 1.09 (95% CI: 0.46-2.56). There was no association of BCRP and ERCC1 expression with disease stage, age, gender or histology. For patients who received cisplatin and irinotecan as first line chemotherapy, there was no difference in survival based on BCRP or ERCC1 status. Conclusions BCRP expression is seen in a majority of esophageal cancers and normal esophageal mucosa. ERCC1 expression is seen in about half of the patients with esophageal cancer. Irinotecan based studies with esophageal and gastric cancer suggest response rates of 14-65%. Whether the 40% of tumors in our study found with down regulation of BCRP expression, constitute a majority of these responders needs to be prospectively validated in a larger data set. It should include markers such as ERCC1 predicting response to 5-fluorouracil and platinum based chemotherapy, to enable individualizing therapy for this cancer. PMID:25083297

  11. Promoter hypermethylation and inactivation of O(6)-methylguanine-DNA methyltransferase in esophageal squamous cell carcinomas and its reactivation in cell lines.

    PubMed

    Fang, Ming Zhu; Jin, Zhe; Wang, Yimin; Liao, Jie; Yang, Guang-Yu; Wang, Li-Dong; Yang, Chung S

    2005-03-01

    The purpose of this study was to characterize the role of DNA hypermethylation in the loss of expression of O(6)-methylguanine-DNA methyltransferase (MGMT) during the development of esophageal squamous cell carcinoma (ESCC) and to investigate its reactivation in cell lines. Samples were collected from Linzhou City of the Henan province in northern China, a high-risk area of this disease. The hypermethylation of promoter CpG islands of the MGMT gene was examined by methylation-specific PCR in ESCC and neighboring non-tumorous tissues, as well as in laser capture microdissected samples with normal epithelium, basal cell hyperplasia (BCH), and dysplasia (DYS). The MGMT mRNA and protein expression were determined with RT-PCR and immunohistochemistry, respectively. Five of 17 (29%) normal, 10 of 20 (50%) BCH, 8 of 12 (67%) DYS, and 13 of 18 (72%) ESCC samples had DNA hypermethylation in the MGMT promoter region, showing a gradual increase with the progression of carcinogenesis. The frequency of the loss of MGMT mRNA and protein expression progressively decreased from normal to BCH, DYS, and ESCC, and it was highly correlated with MGMT promoter hypermethylation according to Fisher's exact tests. When each individual sample was considered, good concordance between DNA hypermethylation and the loss of expression of MGMT was also observed. In samples from the same patient, if hypermethylation was detected in earlier lesions, it was usually observed in more severe lesions. In the ESCC cell line KYSE 510, treatment with a DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine partially reversed the CpG hypermethylation status and restored mRNA expression of the MGMT gene. Similar reactivation of MGMT gene by dietary polyphenols, (-)-epigallocatechin-3-gallate and genistein, has also been observed. The results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing in the development of ESCC, and this epigenetic event may be prevented or reversed by these polyphenols for the prevention of carcinogenesis. PMID:15703815

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

    PubMed

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

    2006-03-01

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

  13. Identification of galectin-7 as a potential biomarker for esophageal squamous cell carcinoma by proteomic analysis

    PubMed Central

    2010-01-01

    Background Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Early diagnosis is critical for guiding the therapeutic management of ESCC. It is imperative to find more effective biomarkers of ESCC. Methods To identify novel biomarkers for esophageal squamous cell carcinoma (ESCC), specimens from 10 patients with ESCC were subjected to a comparative proteomic analysis. The proteomic patterns of ESCC samples and normal esophageal epithelial tissues (NEETs) were compared using two-dimensional gel electrophoresis. And differentially expressed proteins were identified using MALDI-TOF-MS/MS. For further identification of protein in selected spot, western blotting and immunohistochemistry were employed. Results Twelve proteins were up-regulated and fifteen proteins were down-regulated in the ESCC samples compared with the NEET samples. Up-regulation of galectin-7 was further confirmed by western blotting and immunohistochemistry. Furthermore, immunohistochemical staining of galectin-7 was performed on a tissue microarray containing ESCC samples (n = 50) and NEET samples (n = 10). The expression levels of galectin-7 were markedly higher in the ESCC samples than in the NEET samples (P = 0.012). In addition, tissue microarray analysis also showed that the expression level of galectin-7 was related to the differentiation of ESCC. Conclusions The present proteomics analysis revealed that galectin-7 was highly expressed in ESCC tissues. The alteration in the expression of galectin-7 was confirmed using a tissue microarray. These findings suggest that galectin-7 could be used as a potential biomarker for ESCC. PMID:20546628

  14. Congenital esophageal stenosis diagnosed in an infant at 9 month of age.

    PubMed

    Savino, F; Tarasco, V; Viola, S; Locatelli, E; Sorrenti, M; Barabino, A

    2015-01-01

    Esophageal stenosis is a relatively uncommon condition in pediatrics and requires an accurate diagnostic approach. Here we report the case of a 9-month old female infant who presented intermittent vomiting, dysphagia and refusal of solid foods starting after weaning. She was treated for gastroesophageal reflux. At first, radiological investigation suggested achalasia, while esophagoscopy revelaed a severe congenital esophageal stenosis at the distal third of the esophagus. She underwent four endoscopic balloon dilatations that then allowed her to swallow solid food with intermittent mild dysphagia. After 17 months of esomeprazole treatment off therapy impedance-pH monitoring was normal. At 29 months of follow-up the child is asymptomatic and eats without problems.Infants with dysphagia and refusal of solid foods may have undiagnosed medical conditions that need treatment. Many disorders can cause esophageal luminal stricture; in the pediatric age the most common are peptic or congenital. Careful assessment with endoscopy is needed to diagnose these conditions early and referral to a pediatric gastroenterologic unit may be necessary. PMID:26444666

  15. Esophageal mucosa exfoliation induced by oxalic acid poisoning: A case report

    PubMed Central

    WANG, JIERU; KAN, BAOTIAN; JIAN, XIANGDONG; WU, XIAOPENG; YU, GUANCAI; SUN, JING

    2016-01-01

    This study reports the case of a 44-year-old woman with oral oxalic acid poisoning. As the illness progressed, the patient exhibited severe metabolic acidosis, large-area esophageal mucosa injury and acute kidney injury, which required dialysis. A guide wire slipped out of position during the process of hemodialysis and moved back and forth in the veins, but was removed successfully by interventional endovascular treatment. However, the patient's esophageal mucosa exfoliated, which lead to severe benign esophageal stenosis and dysphagia. Balloon distention was conducted twice in the upper digestive tract using X-ray location in combination with a dumb-bell bladder and interventional wire. The patient exhibited convulsions, shock, embolism and loss of consciousness while undergoing the second balloon distention procedure. Following symptomatic treatment, the patient eventually remained in a stable condition, the digestive tract expansion procedure was not resumed and a jejunostomy was performed in order to facilitate enteral nutrition, which was administered via the jejunum and had little stimulatory effect on the pancreas. Following various treatments, the patient's condition improved markedly, with renal function returning to normal. PMID:26889241

  16. XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma.

    PubMed

    Cheng, Jingjing; Liu, Weiran; Zeng, Xianliang; Zhang, Bin; Guo, Yihang; Qiu, Minghan; Jiang, Chao; Wang, Huanhuan; Wu, Zhiqiang; Meng, Maobin; Zhuang, Hongqing; Zhao, Lujun; Hao, Jihui; Cai, Qingqing; Xie, Dan; Pang, Qingsong; Wang, Ping; Yuan, Zhiyong; Qian, Dong

    2015-12-01

    Radiotherapy is widely applied for treatment of esophageal squamous cell carcinoma (ESCC). The Rad51-related protein XRCC3 plays roles in the recombinational repair of DNA double-strand breaks to maintain chromosome stability and repair DNA damage. The present study aimed to investigate the effect of XRCC3 on the radiotherapy response of ESCC and the underlying mechanisms of the roles of XRCC3 in ESCC radiosensitivity. XRCC3 expression in ESCC cells and tissues was higher than that in normal esophageal epithelial cells and corresponding adjacent noncancerous esophageal tissue. High XRCC3 expression was positively correlated with resistance to chemoradiotherapy in ESCC and an independent predictor for short disease-specific survival of ESCC patients. Furthermore, the therapeutic efficacy of radiotherapy in vitro and in vivo was substantially increased by knockdown of XRCC3 in ESCC cells. Ectopic overexpression of XRCC3 in both XRCC3-silenced ESCC cells dramatically enhanced ESCC cells' resistance to radiotherapy. Moreover, radiation resistance conferred by XRCC3 was attributed to enhancement of homologous recombination, maintenance of telomere stability, and a reduction of ESCC cell death by radiation-induced apoptosis and mitotic catastrophe. Our data suggest that XRCC3 protects ESCC cells from ionizing radiation-induced death by promoting DNA damage repair and/or enhancing telomere stability. XRCC3 may be a novel radiosensitivity predictor and promising therapeutic target for ESCC. PMID:26383967

  17. Extra-esophageal manifestations of gastroesophageal reflux disease: diagnosis and treatment.

    PubMed

    Hom, Christopher; Vaezi, Michael F

    2013-08-01

    Gastroesophageal reflux disease (GERD) is a common disease that is often diagnosed based on typical symptoms of heartburn and regurgitation. In addition to these more classic manifestations, GERD is increasingly associated with extra-esophageal symptoms, including chronic cough, asthma, laryngitis, and dental erosions. Due to the poor sensitivity of endoscopy and pH monitoring, and the poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. For those who improve with PPIs, GERD is the presumed etiology, but for those who remain unresponsive to such therapy, further diagnostic testing with impedance/pH monitoring may be necessary in order to exclude refractory acid or weakly acid reflux. In those with normal test results despite PPI therapy and continued symptoms, causes other than GERD may be pursued. Recent data suggest that in patients with extra-esophageal symptoms, objective findings of moderate-sized hiatal hernia and moderate reflux on pH testing may predict response to acid suppressive therapy. PPI-unresponsive patients usually have causes other than GERD for their extra-esophageal symptoms and continued PPI therapy in this group is not recommended. PMID:23881666

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

    PubMed

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

    2016-02-21

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

  19. 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

  20. Chemokine and cytokine expression in murine intestinal epithelium following Nippostrongylus brasiliensis infection.

    PubMed

    Rosbottom, Anne; Knight, Pamela A; McLachlan, Gerry; Thornton, Elizabeth M; Wright, Steven W; Miller, Hugh R P; Scudamore, Cheryl L

    2002-02-01

    Infection of mice with the nematode parasite Nippostrongylus brasiliensis results in a well characterized intestinal mastocytosis with intraepithelial migration of mucosal mast cells (MMC). The molecules mediating this response are unknown. We examined expression of several putative mast cell chemoattractants in intestinal epithelium following N. brasiliensis infection. Expression of the chemokines monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1alpha), RANTES (regulated on activation normal T-cell expressed and secreted), fractalkine, and thymocyte expressed chemokine (TECK); and the cytokines stem cell factor (SCF) and transforming growth factor beta1 (TGFbeta1), was constitutive and no alteration was detected following infection. MCP-1 expression was also constitutive but at much lower levels and increased expression was detected on days 7 and 14 postinfection. Expression of MCP-1 in whole jejunum was at much higher levels than in epithelium. Constitutive expression of MCP-1, MIP-1alpha and TGFbeta1 was also detected in cultured bone marrow-derived homologues of MMC. In an intestinal epithelial cell line (CMT-93), there was constitutive expression of SCF, TGFalpha1, fractalkine and MCP-1. The results show that, in vivo, epithelium is a potentially important source of mast cell chemoattractants. PMID:11874561

  1. Effects of irradiation on canine tracheal epithelium: a physiological and morphological correlate

    SciTech Connect

    Man, S.F.; Logus, J.W.; Mok, K.; Yamamoto, H.; Ahmed, I.H.; Man, G.C.; Hulbert, W.C.

    1987-01-01

    We delivered 20 Gy irradiation in one fraction to a 6 cm segment of trachea in 11 dogs. Tracheal mucous transport was studied before and whenever possible at weekly intervals after irradiation using a gamma camera system and /sup 99m/technetium labeled sulfur colloid. Ten of the eleven animals were sacrificed at three different time intervals (1-2, 15-16 and 30-34 weeks) post-irradiation, and the tracheal epithelium removed for studies using Ussing chambers followed by preparation for microscopic analysis. Mucous transport along the length of the trachea was normal before irradiation, but following irradiation it became abnormal in the irradiated zone. Compared to the epithelium from the cranial and caudal segments, the irradiated epithelium had similar bioelectric measurements (potential difference, short-circuit current and resistance) and mannitol permeability. Also, the changes in the bioelectric measurements following indomethacin (10(-6) M) and epinephrine (10(-6) M) used sequentially, were similar in both the control and irradiated tissues. Scanning electron microscopic analysis of the irradiated zone revealed patches of nonciliated epithelial cells among the ciliates. We conclude that irradiation caused a persistent replacement of ciliated cells with nonciliates throughout the entire study period and that this alteration impaired mucous transport but did not affect epithelial ion secretion or barrier function.

  2. 21 CFR 868.1920 - Esophageal stethoscope with electrical conductors.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal stethoscope with electrical conductors. 868.1920 Section 868.1920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices 868.1920 Esophageal stethoscope with electrical conductors....

  3. 21 CFR 868.1920 - Esophageal stethoscope with electrical conductors.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Esophageal stethoscope with electrical conductors. 868.1920 Section 868.1920 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices § 868.1920 Esophageal stethoscope with electrical conductors....

  4. Esophageal perforation following cervical mediastinoscopy: a rare serious complication

    PubMed Central

    Salter, Benjamin; Evans, Adam; Reddy, Ramachandra

    2015-01-01

    We describe a rare case of esophageal perforation following cervical mediastinoscopy on a patient with mediastinal lymphadenopathy and right upper lobe (RUL) mass. The patient was successfully treated with esophageal stenting and bilateral pleural exploration and drainage with eventual discharge tolerating a regular diet. This report details an uncommon but noteworthy complication to keep in mind when performing this procedure. PMID:26793389

  5. In vitro construction and in vivo regeneration of esophageal bilamellar muscle tissue.

    PubMed

    Hou, Lei; Gong, Changfeng; Zhu, Yabin

    2016-04-01

    In order to induce esophageal muscle cells' orientation, the silicon wafer with prototype 1 and prototype 2 was designed. Prototype 1 has micro-channels of 200 µm width and 30 µm depth with 30 µm wide wall as the interval. Prototype 2 has channels of 100 µm width and 30 µm depth with a discontinuous wall which has 30 µm gap for each 100 µm channel. The poly(ester urethane) scaffolds with pattern prototype 1 and prototype 2 were fabricated using solution casting method and abbreviated as PU1 and PU2, respectively. Silk fibroin was grafted individually on PU1 and PU2 surface (PU1-SF, PU2-SF) using our previous protocol, aiming at improving scaffolds' biocompatibility. The primary esophageal smooth muscle cell was seeded to evaluate the scaffolds' cytocompatibility in vitro. Characterizations like MTT assay, immunocytochemistry, scanning electron microscope, and Western blotting were applied. After that, poly(ester urethane) scaffolds with double patterns, prototype 1 on the exterior, and prototype 2 in the lumen were implanted into the rabbit esophagous to test the regeneration of the muscle tissue. Results from these preliminary tests showed that the growth and differentiation of primary smooth muscle cells were promoted, but also the muscle tissue with endocircular and exolongitudinal architecture was in regenerating, against non-constitution in the animals without the patterned scaffold or with poly(ester urethane) plane membrane at the defaulted sites. This micro-channel pattern together with silk fibroin grafting and vascular endothelial growth factor coating greatly promoted the regeneration of esophageal muscle with normal histological structure. PMID:26823400

  6. Eosinophilic esophagitis in patients with typical gastroesophageal reflux disease symptoms refractory to proton pump inhibitor

    PubMed Central

    de S, Cludia Cristina; Kishi, Humberto Setsuo; Silva-Werneck, Ana Luiza; de MoraesFilho, Joaquim Prado Pinto; Eisig, Jaime Natan; Barbuti, Ricardo Correa; Hashimoto, Cludio Lyioti; Navarro-Rodriguez, Tomas

    2011-01-01

    BACKGROUND: TREATMEN The contribution of eosinophilic esophagitis (EoE) to refractory gastroesophageal reflux disease (GERD) remains unknown. When EoE and GERD overlap, the clinical, endoscopic and histological findings are nonspecific and cannot be used to distinguish between the two disorders. Limited data are available on this topic, and the interaction between EoE and GERD is a matter of debate. AIM: We have conducted a prospective study of adult patients with refractory GERD to evaluate the overlap of reflux and EoE. METHODS: Between July 2006 and June 2008, we consecutively and prospectively enrolled 130 male and female patients aged 18 to 70 years old who experienced persistent heartburn and/or regurgitation more than twice a week over the last 30 days while undergoing at least six consecutive weeks of omeprazole treatment (at least 40mg once a day). The patients underwent an upper digestive endoscopy with esophageal biopsy, and intraepithelial eosinophils were counted after hematoxylin/eosin staining. The diagnosis of EoE was based on the presence of 20 or more eosinophils per high-power field (eo/HPF) in esophageal biopsies. RESULTS: Among the 103 studied patients, 79 (76.7%) were females. The patients had a mean age of 45.5 years and a median age of 47 years. Endoscopy was normal in 83.5% of patients, and erosive esophagitis was found in 12.6%. Only one patient presented lesions suggestive of EoE. Histological examination revealed >20eo/HPF in this patient. CONCLUSION: Our results demonstrated a low prevalence of EoE among patients with refractory GERD undergoing omeprazole treatment. PMID:21655746

  7. [Atrophy of retinal pigment epithelium after macular hole surgery].

    PubMed

    Cerbulescu, Beatrice; Crstocea, B; Buliga, Simona; Gheorghieva, Valeria; Taina, Ana-Lavinia

    2010-01-01

    We present three cases of macular hole. After macular surgery we observed good anatomical results (closed macular holes) but poor functional results. We try to identified the element who produced atrophy of retinal pigment epithelium. PMID:20540371

  8. Spectrum of FDG uptake in large (>10 cm) esophageal leiomyomas

    PubMed Central

    Dendy, Meaghan; Johnson, Katelyn

    2015-01-01

    Esophageal leiomyomas are rare benign tumors that can be treated successfully with limited surgical resection. It is occasionally important to distinguish leiomyomas from more aggressive submucosal esophageal tumors, most notably gastrointestinal stromal tumors (GISTs). GISTs have a worse prognosis, particularly when they are large (>10 cm). Increased uptake of 18F-fluorodeoxyglucose on positron emission tomography (PET) scans is common in GISTs, potentially allowing PET scanning to differentiate between GIST and benign esophageal tumors. Three patients presented with large (>10 cm) esophageal masses of ranging PET avidity [maximum standardized uptake value (SUVmax) of 1.310.1]. All were treated surgically and histologically confirmed to be esophageal leiomyomas. Unfortunately, the wide range of PET uptake precludes PET scanning from differentiating large leiomyomas from more aggressive lesions. PMID:26793383

  9. Spectrum of FDG uptake in large (>10 cm) esophageal leiomyomas.

    PubMed

    Dendy, Meaghan; Johnson, Katelyn; Boffa, Daniel J

    2015-12-01

    Esophageal leiomyomas are rare benign tumors that can be treated successfully with limited surgical resection. It is occasionally important to distinguish leiomyomas from more aggressive submucosal esophageal tumors, most notably gastrointestinal stromal tumors (GISTs). GISTs have a worse prognosis, particularly when they are large (>10 cm). Increased uptake of (18)F-fluorodeoxyglucose on positron emission tomography (PET) scans is common in GISTs, potentially allowing PET scanning to differentiate between GIST and benign esophageal tumors. Three patients presented with large (>10 cm) esophageal masses of ranging PET avidity [maximum standardized uptake value (SUVmax) of 1.3-10.1]. All were treated surgically and histologically confirmed to be esophageal leiomyomas. Unfortunately, the wide range of PET uptake precludes PET scanning from differentiating large leiomyomas from more aggressive lesions. PMID:26793383

  10. Expression of cyclooxygenase-2 in human esophageal squamous cell carcinomas

    PubMed Central

    Jiang, Jian-Gang; Tang, Jiang-Bo; Chen, Chun-Lian; Liu, Bao-Xing; Fu, Xiang-Ning; Zhu, Zhi-Hui; Qu, Wei; Cianflone, Katherine; Waalkes, Michael P.; Wang, Dao-Wen

    2004-01-01

    AIM: To determine whether cyclooxygenase-2 (COX-2) was expressed in human esophageal squamous cell carcinoma. METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, immunohistoc-hemistry and immunofluorescence were used to assess the expression level of COX-2 in esophageal tissue. RESULTS: COX-2 mRNA levels were increased by > 80-fold in esophageal squamous cell carcinoma when compared to adjacent noncancerous tissue. COX-2 protein was present in 21 of 30 cases of esophageal squamous cell carcinoma tissues, but was undetectable in noncancerous tissue. Immunohistochemistry was performed to directly show expression of COX-2 in tumor tissue. CONCLUSION: These results suggest that COX-2 may be an important factor for esophageal cancer and inhibition of COX-2 may be helpful for prevention and possibly treatment of this cancer. PMID:15259059

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

    PubMed

    Ross-Innes, Caryn S; Becq, Jennifer; 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

    2015-09-01

    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 the following new insights: (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 the capacity to reflect the entire clonal architecture. PMID:26192915

  12. Advanced esophageal cancer with tracheobronchial fistula successfully treated by?esophageal bypass surgery

    PubMed Central

    Kimura, Masahiro; Ishiguro, Hideyuki; Tanaka, Tatsuya; Takeyama, Hiromitsu

    2015-01-01

    Introduction When esophageal cancer infiltrates the respiratory tract and forms a fistula, a patients quality of life falls remarkably. Abstinence from oral feeding is necessary to prevent respiratory complications including pneumonia. Surgery is sometimes necessary to maintain quality of life. The aim of this study was to examine clinical outcomes of esophageal cancer complicated by tracheobronchial fistula. Presentation of case Twelve patients who underwent esophageal bypass between 2006 and 2011 in our hospital were studied. Patient characteristics, therapeutic course, outcome, and operation type were compared. Six patients among 8 who could not tolerate oral feeding could do so after bypass surgery. Ten patients were able to enjoy oral intake up until the last few days of life. Three patients survived for more than 10 months. In spite of undergoing an operation, 1 patient survived for only 2 months and another for 4 months. The only complication was postoperative delirium in 1 patient. Discussion While surgical bypass is more invasive than procedures such as endoscopic stenting, we had few complications after operative intervention and were able to maintain quality of life in our patients. Conclusion This bypass procedure is a treatment option for patients with tracheobronchial fistula from advanced esophageal cancer. PMID:25765740

  13. Emerging techniques and efficacy of endoscopic esophageal reconstruction and lumen restoration for complete esophageal obstruction

    PubMed Central

    Perbtani, Yaseen; Suarez, Alejandro L.; Wagh, Mihir S.

    2016-01-01

    Background and study aims: Complete esophageal obstruction (CEO) is a rare occurrence characterized by progressive esophageal stricture, which eventually causes lumen obliteration. With recent advances in flexible endoscopy, various innovative techniques exist for restoring luminal continuity. The primary aim of this study was to assess the efficacy and safety of patients undergoing combined antegrade-retrograde endoscopic dilation for CEO at our institution. The secondary aim was to review and highlight emerging techniques, outcomes, and adverse events after endoscopic treatment of CEO. Patients and methods: Our electronic endoscopy database was retrospectively reviewed to identify patients who underwent combined antegrade and retrograde endoscopy for CEO. Patient and procedural data collected included gender, age, technical success, pre- and post-dysphagia scores, and adverse events. Results: Six patients (67 % male, mean age 71.6 years [range 63 – 80]) underwent technically successful esophageal reconstruction with combined antegrade-retrograde endoscopy. All patients noted improvement in dysphagia with mean pre-procedure dysphagia score of 4 reduced to 1.33 (range 0 – 3) post-procedure. There were no adverse events and mean follow-up time was 17.3 months (range 3 – 48). Conclusions: Combined antegrade and retrograde endoscopic therapy for CEO is feasible and safe. We present our experience with endoscopic management of complete esophageal obstruction, and highlight emerging techniques, outcomes and adverse events related to this minimally invasive modality. PMID:26878039

  14. Biochemical studies of isolated hamster tracheal epithelium.

    PubMed Central

    Kaufman, D G

    1976-01-01

    The epithelial lining of respiratory air passageways is a primary target tissue for toxicity and carcinogenesis in man and in animal models of human disease. The importance of this target tissue was the basis for development of methods to study its biochemistry, and with this information to distinguish the unique properties of this tissue from properties common to all cell types. Biochemical methods employed labeling of macromolecules in isolated hamster treacheas during brief (less than 4 hr) incubation in vitro. Studies of RNA metabolism in isolated tracheas demonstrated a pattern of maturation of ribosomal RNA like that shown for other cell types. Alterations in RNA metabolism were observed in isolated tracheas obtained from vitamin A-deficient hamsters and hamsters previously treated by intratracheal administration of benzo[a]pyrene (BP) plus ferric oxide (Fe2O3) in vivo. Studies with toyocamycin, actinomycin D, and alpha-amanitin, all inhibitors of RNA metabolism, were performed to characterize the class of RNA molecules with a decreased proportion of labeling in tracheas from vitamin A deficient hamsters. In another series of experiments, BP was shown to bind to DNA in epithelial cells of isolated tracheas. The quantity of BP binding was increased by prior intratracheal treatment of hamsters with BP plus Fe2O3 in vivo, this induced binding was inhibited by addition of 7,8-benzoflavone to the incubation medium. Increased BP binding was also observed in isolated tracheas from hamsters believed to be in states of increased susceptibility to respiratory carcinogenesis in vivo. The results show that biochemical studies are feasible with this tissue. Furthermore, a number of questions of importance with regard to this target epithelium are best studied directly in its constituent cells. PMID:1017424

  15. Ultrasonographic study of postcibal gastro-esophageal reflux and gastric emptying in infants with recurrent respiratory disease

    PubMed Central

    Ciaula, Agostino Di; Portincasa, Piero; Terlizzi, Leonardo Di; Paternostro, Domenico; Palasciano, Giuseppe

    2005-01-01

    AIM: To check the utility of postcibal ultrasonography for the evaluation of reflux in relation to gastric emptying in infants with recurrent respiratory symptoms and to link imaging with clinical data. METHODS: Esophageal reflux (hyperechoic retrograde filling) and gastric emptying (antral areas) were quantified before and after ingestion of a standard formula in 35 untreated infants (13 with chronic cough, 22 with recurrent bronchitis) and in 31 controls. RESULTS: The prevalence of abnormal (?8 episodes) postcibal refluxes was 74% in patients and 3% in controls. Number, duration of the longest episode and extent of refluxes were significantly higher in patients compared to controls. Number of refluxes was higher in patients with symptomatic refluxes than in those without. Infants with recurrent bronchitis had more refluxes than those with chronic cough and controls. Extent and timing of gastric emptying were similar in patients and controls. CONCLUSION: Esophageal ultrasonography is a useful and physiological test in infants with recurrent respiratory diseases, which have a high prevalence of abnormal postcibal esophageal reflux and a gastric emptying similar to that of normal controls. Esophageal reflux is more severe in subjects with recurrent bronchitis than in those with chronic cough. PMID:16437631

  16. The Effect of Beta-Aminopropionitrile and Prednisolone on the Prevention of Fibrosis in Alkali Esophageal Burns: An Experimental Study

    PubMed Central

    Aciksari, Kurtulus; Yanar, Hakan Teoman; Hepgul, Gulcin; Yanar, Fatih; Agcaoglu, Orhan; Eser, Mediha; Tanriverdi, Gamze; Topacoglu, Hakan; Ayvaci, Baris Murat; Dogan, Halil; Gunay, Kayihan; Ertekin, Cemalettin; Celikmen, Ferudun

    2013-01-01

    Objective. The aim of this study was to investigate the efficacy of beta-aminopropionitrile (BAPN) and prednisolone on the prevention of esophageal damage and stricture formation after caustic esophageal burn. Method. Twenty-eight rats were divided into four equal groups. In groups 1, 2, and 3, caustic esophageal burns were generated by applying NaOH to the 1.5 cm segment of the abdominal esophagus. Group 4 was for the sham. Normal saline to group 1, BAPN to group 2, and prednisolone to group 3 were administered intraperitoneally as a single daily dose. Results. Treatment with BAPN decreased the stenosis index (SI) and histopathologic damage score (HDS) seen in caustic esophageal burn rats. The SI in group 4 was significantly lower compared with groups 1, 2, and 3. Group 2 had the minimum SI value in corrosive burn groups. The differences related to SI between groups 1, 2, and 3 were not statistically significant. The HDS was significantly lower in group 4 compared with groups 1, 2, and 3. The HDS in group 2 was significantly lower compared with groups 1 and 3. Conclusion. This study demonstrated that BAPN was able to decrease the development of stenosis and tissue damage better than prednisolone. PMID:24391