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Sample records for normal esophageal epithelium

  1. Critical role of p63 in the development of a normal esophageal and tracheobronchial epithelium.

    PubMed

    Daniely, Yaron; Liao, Grace; Dixon, Darlene; Linnoila, R Ilona; Lori, Adriana; Randell, Scott H; Oren, Moshe; Jetten, Anton M

    2004-07-01

    The trachea and esophagus originate from the foregut endoderm during early embryonic development. Their epithelia undergo a series of changes involving the differentiation of stem cells into unique cell types and ultimately forming the mature epithelia. In this study, we monitored the expression of p63 in the esophagus and the trachea during development and examined in detail morphogenesis in p63(-/-) mice. At embryonic day 15.5 (E15.5), the esophageal and tracheobronchial epithelia contain two to three layers of cells; however, only the progenitor cells express p63. These progenitor cells differentiate first into ciliated cells (p63(-)/beta-tubulin IV(+)) and after birth into mature basal cells (p63(+)/K14(+)/K5(+)/BS-I-B4(+)). In the adult pseudostratified, columnar tracheal epithelium, K14(+)/K5(+)/BS-I-B4(+) basal cells stain most intensely for p63, whereas ciliated and mucosecretory cells are negative. In stratified squamous esophageal epithelium and during squamous metaplasia in the trachea, cells in the basal layer stain strongest for p63, whereas p63 staining declines progressively in transient amplifying and squamous differentiated cells. Generally, p63 expression is restricted to human squamous cell carcinomas, and adenocarcinomas and Barrett's metaplasia do not stain for p63. Examination of morphogenesis in newborn p63(-/-) mice showed an abnormal persistence of ciliated cells in the esophagus. Significantly, in both tissues, lack of p63 expression results in the development of a highly ordered, columnar ciliated epithelium deficient in basal cells. These observations indicate that p63 plays a critical role in the development of normal esophageal and tracheobronchial epithelia and appears to control the commitment of early stem cells into basal cell progeny and the maintenance of basal cells. PMID:15189821

  2. 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

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

    PubMed Central

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

    2013-01-01

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

  4. Hyaluronan distribution in the normal epithelium of esophagus, stomach, and colon and their cancers.

    PubMed Central

    Wang, C.; Tammi, M.; Guo, H.; Tammi, R.

    1996-01-01

    The distribution of hyaluronan (HA) in normal gastrointestinal wall and in tumors originating from their epithelium was studied using a specific probe prepared from cartilage proteoglycan (bHABC, biotinylated hyaluronan binding complex). The normal stratified squamous epithelium of esophagus showed an intense HA staining in the basal and lower intermediate layers, whereas the simple epithelia in the stomach and large intestine were HA negative. Esophageal in situ carcinomas expressed HA also in the cell layers close to the luminal surface, in regions normally negative. Most of the invasive squamous cell carcinomas maintained their HA expression, but in very poorly differentiated types the tumor parenchyma was devoid of HA. In both gastric and colonic adenocarcinomas the tumor parenchyma showed no HA. The stromal tissue was intensely HA positive in all tumors. Cancer cells invading the intestinal smooth muscle were surrounded by copious amounts of HA, whereas the muscular layer was otherwise very poor in HA staining. These results show that relatively well differentiated carcinoma cells themselves retain the high or low HA expression pattern of their original epithelium, whereas tumors stimulate HA deposition in the surrounding stroma. Images Figure 1 Figure 2 Figure 3 PMID:8669472

  5. 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

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

    PubMed

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

    2015-06-01

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

  7. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make ... Epithelium. In: Kierszenbaum AL, Tres LL. Histology and Cell Biology - An Introduction to Pathology , 3rd ed. Philadelphia, ...

  8. Alcohol consumption is associated with an increased risk of erosive esophagitis and Barrett's epithelium in Japanese men

    PubMed Central

    Akiyama, Tomoyuki; Inamori, Masahiko; Iida, Hiroshi; Mawatari, Hironori; Endo, Hiroki; Hosono, Kunihiro; Yoneda, Kyoko; Fujita, Koji; Yoneda, Masato; Takahashi, Hirokazu; Goto, Ayumu; Abe, Yasunobu; Kobayashi, Noritoshi; Kubota, Kensuke; Saito, Satoru; Nakajima, Atsushi

    2008-01-01

    Background Evidence regarding the association between alcohol consumption and the gastro-esophageal reflux disease (GERD) spectrum has been conflicting. We examined the association between alcohol consumption and erosive esophagitis and Barrett's epithelium in Japanese men. Methods The study population comprised 463 men subjects who had undergone an upper endoscopy at the Gastroenterology Division of Yokohama City University Hospital between August 2005 and July 2006. The presence of erosive esophagitis and Barrett's epithelium was diagnosed based on the Los Angeles Classification and the Prague C and M Criteria, respectively. We divided the study population into four groups: never drinkers, light drinkers (less than 25.0 g of ethanol per day), moderate drinkers (25.0 to 50.0 g of ethanol per day), and heavy drinkers (more than 50.0 g of ethanol per day). A linear regression of the logistic regression analysis was used to analyze the dose-response trends. Results Compared with never drinkers, light drinkers (less than 25.0 g ethanol per day), moderate drinkers (25.0 to 50.0 g per day), and heavy drinkers (more than 50.0 g per day) had ORs for erosive esophagitis of 1.110 (95% CI: 0.553 – 2.228, p = 0.7688), 1.880 (95% CI: 1.015 – 3.484, p = 0.0445) and 1.988 (95% CI: 1.120 – 3.534, p = 0.0190), respectively. These groups had ORs for Barrett's epithelium of 1.278 (95% CI: 0.752 – 2.170, p = 0.3643), 1.458 (95% CI: 0.873 – 2.433, p = 0.1500), and 1.912 (95% CI: 1.185 – 3.086, p = 0.0079), respectively. The odds ratios/grams (alcohol)/day of dose response trends for erosive esophagitis and Barrett's epithelium were 1.015 (95% CI: 1.004–1.026, p = 0.0066) and 1.012 (95% CI: 1.003–1.021, p = 0.0079), respectively. Conclusion These findings suggest that alcohol consumption in Japanese men tends to be associated with an increased risk of erosive esophagitis and Barrett's epithelium. PMID:19077221

  9. LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium

    PubMed Central

    D’Mello, RJ; Caldwell, JM; Azouz, NP; Wen, T; Sherrill, JD; Hogan, SP; Rothenberg, ME

    2015-01-01

    Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus featuring increased esophageal interleukin 13 (IL-13) levels and impaired barrier function. Herein, we investigated leucine-rich repeat–containing protein 31 (LRRC31) in human EoE esophageal tissue and IL-13–treated esophageal epithelial cells. LRRC31 had basal mRNA expression in colonic and airway mucosal epithelium. Esophageal LRRC31 mRNA and protein increased in active EoE and strongly correlated with esophageal eosinophilia and IL13 and CCL26 mRNA expression. IL-13 treatment increased LRRC31 mRNA and protein in air-liquid interface–differentiated esophageal epithelial cells (EPC2s). At baseline, differentiated LRRC31-overexpressing EPC2s had increased barrier function (1.9-fold increase in transepithelial electrical resistance [P < 0.05] and 2.8-fold decrease in paracellular flux [P < 0.05]). RNA sequencing analysis of differentiated LRRC31-overexpressing EPC2s identified 38 dysregulated genes (P < 0.05), including 5 kallikrein (KLK) serine proteases. Notably, differentiated LRRC31-overexpressing EPC2s had decreased KLK expression and activity, whereas IL-13–treated, differentiated LRRC31 gene-silenced EPC2s had increased KLK expression and suprabasal epithelial detachment. We identified similarly dysregulated KLK expression in the esophagus of patients with active EoE and in IL-13–treated esophageal epithelial cells. We propose that LRRC31 is induced by IL-13 and modulates epithelial barrier function, potentially through KLK regulation. PMID:26462420

  10. 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...

  11. 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...

  12. Demonstration of substances of innate immunity in the esophageal epithelium of domesticated mammals: Part II--Defence mechanisms, including species comparison.

    PubMed

    Nina Hornickel, Isabelle; Kacza, Johannes; Schnapper, Anke; Beyerbach, Martin; Schoennagel, Britta; Seeger, Johannes; Meyer, Wilfried

    2011-02-01

    The second part of our study deals with a comparative evaluation and discussion of the immunohistochemical results that were obtained. The cryoscanning electron microscopy (cryoSEM) observations confirmed a monolayer colonization of the esophageal surface with bacteria and fungi (yeasts); the latter in particular was prominent in the ruminant species studied. We demonstrated the existence of several innate immune parameters, including pathogen recognition receptors (PRRs), such as Toll-like receptor 2, which was primarily expressed in the stratum basale; however, the presence β-glucan receptors remained inconclusive. Furthermore, the group of cationic antimicrobial peptides (CAPs) was shown, comprising β-defensins 2 and 3 and cathelicidin. The less keratinized esophageal epithelium of the carnivorous cat was protected by high amounts of CAPs; whereas the more strongly keratinized epithelium of the herbivorous and omnivorous species with its characteristic layer structure exhibited clearly weaker reactions. Moreover, lysozyme could distinctly be demonstrated in the cells of the esophageal epithelium. It can be concluded that a first line of defence mechanisms of the innate immune system contributes to maintaining a microbial homeostasis on the surface of the esophageal epithelium of domesticated mammals. The results are discussed in comparison to findings from studies on the human esophagus. PMID:20022082

  13. Prognostic Value and Targeted Inhibition of Survivin Expression in Esophageal Adenocarcinoma and Cancer-Adjacent Squamous Epithelium

    PubMed Central

    Malhotra, Usha; Zaidi, Ali H.; Kosovec, Juliann E.; Kasi, Pashtoon M.; Komatsu, Yoshihiro; Rotoloni, Christina L.; Davison, Jon M.; R, Clint; Irvin; Hoppo, Toshitaka; Nason, Katie S.; Kelly, Lori A.; Gibson, Michael K.; Jobe, Blair A.

    2013-01-01

    Background Survivin is an inhibitor of apoptosis and its over expression is associated with poor prognosis in several malignancies. While several studies have analyzed survivin expression in esophageal squamous cell carcinoma, few have focused on esophageal adenocarcinoma (EAC) and/or cancer-adjacent squamous epithelium (CASE). The purpose of this study was 1) to determine the degree of survivin up regulation in samples of EAC and CASE, 2) to evaluate if survivin expression in EAC and CASE correlates with recurrence and/or death, and 3) to examine the effect of survivin inhibition on apoptosis in EAC cells. Methods Fresh frozen samples of EAC and CASE from the same patient were used for qRT-PCR and Western blot analysis, and formalin-fixed, paraffin-embedded tissue was used for immunohistochemistry. EAC cell lines, OE19 and OE33, were transfected with small interfering RNAs (siRNAs) to knockdown survivin expression. This was confirmed by qRT-PCR for survivin expression and Western blot analysis of cleaved PARP, cleaved caspase 3 and survivin. Survivin expression data was correlated with clinical outcome. Results Survivin expression was significantly higher in EAC tumor samples compared to the CASE from the same patient. Patients with high expression of survivin in EAC tumor had an increased risk of death. Survivin expression was also noted in CASE and correlated with increased risk of distant recurrence. Cell line evaluation demonstrated that inhibition of survivin resulted in an increase in apoptosis. Conclusion Higher expression of survivin in tumor tissue was associated with increased risk of death; while survivin expression in CASE was a superior predictor of recurrence. Inhibition of survivin in EAC cell lines further showed increased apoptosis, supporting the potential benefits of therapeutic strategies targeted to this marker. PMID:24223792

  14. 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

  15. Esophagitis

    MedlinePlus

    Esophagitis is often caused by stomach fluid that flows back into the esophagus. The fluid contains acid which irritates the tissue. This problem is called gastroesophageal reflux . An autoimmune disorder called ...

  16. Esophagitis

    MedlinePlus

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

  17. 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.

  18. Multichannel intraluminal impedance and esophageal manometry data for unrestricted swallowing: establishing normal values.

    PubMed

    Wilson, J A; Mainie, I; Tutuian, R; Agrawal, A; Castell, D O

    2008-01-01

    Standard esophageal manometric testing evaluates swallowing in the supine position using small boluses, with a recovery period imposed between swallows. Manometric tests of more physiologic unrestricted swallowing have had limited practical application due to highly variable results. The purpose of this study is to apply multichannel intraluminal impedance and manometry (MII-EM) to test esophageal function during unrestricted upright meal consumption, and to assess results in a normal healthy population. Ten healthy volunteers with normal esophageal impedance and manometry by published criteria underwent MII-EM testing using a combined 5-channel catheter. After transnasal placement of the catheter, each subject sat upright and consumed a meal that consisted of two pieces of toasted bread and two ounces of Gatorade. There were no restrictions placed on chewing, swallowing, or eating time. All data assessed by the MII-EM meal test were normally distributed. Impedance results with limited variability included the meal duration, number of swallows, postprandial emptying time and the percent of bolus presence times at 15, 10, and 5 cm above the lower esophageal sphincter. Manometric results with limited variability included the number of peristaltic sequences, mean time between these sequences and their distal esophageal amplitudes. MII-EM can be used to collect data with minimal variability in healthy subjects during unrestricted upright meal consumption. This technique may be used to identify abnormal motility patterns during physiologic swallowing. PMID:18197939

  19. Downregulation of p63 upon exposure to bile salts and acid in normal and cancer esophageal cells in culture.

    PubMed

    Roman, Sabine; Pétré, Aurélia; Thépot, Amélie; Hautefeuille, Agnès; Scoazec, Jean-Yves; Mion, François; Hainaut, Pierre

    2007-07-01

    p63 is a member of the p53 protein family that regulates differentiation and morphogenesis in epithelial tissues and is required for the formation of squamous epithelia. Barrett's mucosa is a glandular metaplasia of the squamous epithelium that develops in the lower esophagus in the context of chronic, gastroesophageal reflux and is considered as a precursor for adenocarcinoma. Normal or squamous cancer esophageal cells were exposed to deoxycholic acid (DCA, 50, 100, or 200 microM) and chenodeoxycholic and taurochenodeoxycholic acid at pH 5. p63 and cyclooxygenase-2 (COX-2) expressions were studied by Western blot and RT-PCR. DCA exposure at pH 5 led to a spectacular decrease in the levels of all isoforms of the p63 proteins. This decrease was observed within minutes of exposure, with a synergistic effect between DCA and acid. Within the same time frame, levels of p63 mRNA were relatively unaffected, whereas levels of COX-2, a marker of stress responses often induced in Barrett's mucosa, were increased. Similar results were obtained with chenodeoxycholic acid but not its taurine conjugate at pH 5. Proteasome inhibition by lactacystin or MG-132 partially blocked the decrease in p63, suggesting a posttranslational degradation mechanism. These results show that combined exposure to bile salt and acid downregulates a critical regulator of squamous differentiation, providing a mechanism to explain the replacement of squamous epithelium by a glandular metaplasia upon exposure of the lower esophagus to gastric reflux. PMID:17615180

  20. 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

  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. Cyclin dependent kinase inhibitor p27Kip1 expression in normal and neoplastic cervical epithelium.

    PubMed Central

    Troncone, G; Vetrani, A; de Rosa, G; Gerbasio, D; Palombini, L

    1999-01-01

    AIM: To investigate whether there is loss of the p27Kip1 protein in developing cervical cancer and whether p27Kip1 immunoreactivity has any relation to the proliferative indicator Ki-67. METHODS: The expression of p27Kip1 and Ki-67 was assessed by immunohistochemistry in serial sections from normal epithelium (13), low grade (27) and high grade (19) squamous intraepithelial lesions (LSIL, HSIL), and invasive cervical cancer (23). In the SIL cases the presence of human papillomavirus (HPV) genomic sequences was assessed by in situ hybridisation. The results were evaluated by image analysis, and reported as mean score of the percentage of p27Kip1 and of Ki-67 positive cells in each histological group. RESULTS: In general, p27Kip1 immunostaining was related to squamous differentation, and was intense in normal epithelium (47%), while it was reduced in SIL lesions as an effect of the decreased number of differentiating cells. However, decrease in the p27Kip1 expression was more evident in LSIL (36%) than in HSIL (39%); in the latter, p27Kip1 had a different intraepithelial distribution in that the staining extended to the basal cells. The average levels of p27Kip1 were similar in SIL lesions associated to low, intermediate, and high risk HPV types. Compared with normal epithelium and dysplasia, invasive cancer showed significantly lower p27Kip1 levels (23%). There was no relation between p27Kip1 and Ki-67 labelling indices in any of the histological groups examined. CONCLUSIONS: A reduction in p27Kip1 protein occurs in cervical cancer independently of the proliferative status. The changes in p27Kip1 expression may be related to the unregulated kinetics of developing cervical cancer. Images PMID:10711250

  3. Normal 24-hour Ambulatory Esophageal pH Values in Koreans

    PubMed Central

    Moon, Won; Kim, Gyung Mi; Kim, Kyu Jong; Park, Seun Ja; Mun, Hyo Sung; Lee, Kang Dae

    2008-01-01

    Background/Aims Twenty-four-hour ambulatory esophageal pH monitoring is considered the gold standard for diagnosing gastroesophageal reflux disease. The aim of this study was to quantify normal distal esophageal acid parameters in healthy Koreans. Methods Thirty healthy adults who were not on medication and were free from gastrointestinal symptoms were analyzed. Ambulatory esophageal acid (pH <4) exposure parameters were recorded at 5 cm above the lower esophageal sphincter. Results The 95th percentiles for reflux parameters assessed in the distal esophagus were as follows: percentage of total time with pH <4, 5.10%; percentage of upright time with pH <4, 7.88%; percentage of supine time with pH <4, 4.00%; number of reflux episodes, 62.7; number of reflux episodes with pH <4 for >5 minutes, 5.3; and the longest single acid-exposure episode, 21.3 minutes. Conclusions Physiological gastroesophageal reflux occurs frequently in healthy Koreans. These data provide a reference range that could be utilized in studies involving Korean subjects. PMID:20485604

  4. In vivo antioxidant gene expression in human airway epithelium of normal individuals exposed to 100% O2.

    PubMed

    Erzurum, S C; Danel, C; Gillissen, A; Chu, C S; Trapnell, B C; Crystal, R G

    1993-09-01

    Human bronchial epithelium is exquisitely sensitive to high O2 levels, with tracheobronchitis usually developing after 12 h of exposure to 100% O2. To evaluate whether this vulnerability results from inability of the bronchial epithelium to provide adequate antioxidant protection, we quantified antioxidant gene expression in bronchial epithelium of normal volunteers at baseline and after exposure to 100% O2 in vivo. After 14.8 +/- 0.2 h of 100% O2, 24 of 33 individuals had evidence of tracheobronchitis. Baseline gene expression of CuZn superoxide dismutase (SOD), MnSOD, and catalase in bronchial epithelium was very low (CuZnSOD 4.1 +/- 0.8 transcripts/cell, MnSOD 5.1 +/- 0.9, catalase 1.3 +/- 0.2), with control gamma-actin expression relatively abundant (50 +/- 6 transcripts/cell). Importantly, despite 100% O2 exposure sufficient to cause tracheobronchitis in most individuals, antioxidant mRNA transcripts/cell in bronchial epithelium did not increase (P > 0.5). Catalase activity in bronchial epithelium did not change after exposure to hyperoxia (P > 0.05). Total SOD activity increased mildly (P < 0.01) but not sufficiently to protect the epithelium. Together, the very low levels of expression of intracellular antioxidant enzymes and the inability to upregulate expression at the mRNA level with oxidant stress likely have a role in human airway epithelium susceptibility to hyperoxia. PMID:8226538

  5. Current smoking-specific gene expression signature in normal bronchial epithelium is enhanced in squamous cell lung cancer.

    PubMed

    Boelens, Mirjam C; van den Berg, Anke; Fehrmann, Rudolf S N; Geerlings, Marie; de Jong, Wouter K; te Meerman, Gerard J; Sietsma, Hannie; Timens, Wim; Postma, Dirkje S; Groen, Harry J M

    2009-06-01

    Cigarette smoking is the main risk factor for the development of squamous cell lung carcinoma (SCC). However, the smoking-related molecular changes in SCC have not been studied. Gene expression studies in both histologically normal bronchial epithelium and SCC epithelial samples identified genes differentially expressed between current and ex-smokers. Subsequently, expression levels of the smoking-related genes in normal bronchial epithelium were compared with those in SCC cells, since we hypothesized that the smoking-induced changes would be also deregulated in SCC. Gene expression profiles were generated using Agilent whole human genome microarrays on laser-microdissected normal bronchial epithelium and SCC samples. Expression levels of 246 genes, mainly related to oxidative stress response, were significantly different between normal bronchial epithelium of current and ex-smokers. Such a differential gene expression profile did not exist in SCC cells of smokers and ex-smokers. Interestingly, when comparing SCC and normal bronchial epithelium from ex-smokers, the vast majority of these 246 genes were also deregulated in SCC. When comparing SCC with normal epithelium from smokers, 22% of the up-regulated genes showed a similar high expression in SCC whereas 79% of the down-regulated genes were even further reduced in SCC as compared to current smokers. The down-regulated genes included several tumour suppressor genes, such as C9orf9, INHBB, LRIG1, SCGB3A1, SERPINI2, STEAP3 and ZMYND10. Thus, our study shows that the majority of genes up-regulated in normal bronchial epithelium of current smokers show similar high expression levels in SCC, while down-regulated genes are even further repressed in SCC. Our data indicate that smoking-related changes in normal bronchial epithelial cells persist in malignant transformed squamous cells. PMID:19334046

  6. Detection of aryl hydrocarbon hydroxylase activity in normal and neoplastic human breast epithelium

    SciTech Connect

    Greiner, J.W.; Malan-Shibley, L.B.; Janss, D.H.

    1980-01-28

    Studies were conducted to determine whether normal and/or neoplastic (MCF-7) human breast epithelial cells contain the microsomal aryl hydrocarbon hydroxylase (AHH) which catalyses the conversion of polycyclic aromatic hydrocarbons (PAH) to carcinogenic intermediates. Low constitutive levels of AHH activity were found in homogenates of both normal human breast epithelial and MCF-7 cells. The addition of 7,12-dimethylbenz(a)anthracene (DMBA) to the culture medium of either cell type significantly increased AHH activity. Peak induction of hydroxylase activity occurred following the in vitro addition of 10 ..mu..M DMBA. A time course of DMBA-induced AHH activity in both normal human breast epithelium and MCF-7 cells revealed maximal induction 16 hr after 10 ..mu..M DMBA was added to the culture medium. Benzo(a)pyrene (BP), 3-methylcholanthrene (MCA) and benz(a)anthracene (BA) also induced AHH activity in normal and MCF-7 cells. For example, the addition of 10 ..mu..M BP to the culture medium of either normal human breast epithelial or MCF-7 cells for 16 hr increased AHH activity 13.8 and 65.3-fold, respectively. For all PAH, the magnitude of AHH induction was substantially greater in MCF-7 than normal breast epithelial cells. Finally, ..cap alpha..-naphthoflavone inhibited BA-induced AHH activity in MCF-7 cells. The study demonstrates the presence of a PAH-inducible AHH enzyme(s) in normal human breast epithelial cells grown in primary culture and in the human breast tumor cell line, MCF-7.

  7. Demonstration of substances of innate immunity in the esophageal epithelium of domesticated mammals. Part I--Methods and evaluation of comparative fixation.

    PubMed

    Nina Hornickel, Isabelle; Kacza, Johannes; Schnapper, Anke; Beyerbach, Martin; Schoennagel, Britta; Seeger, Johannes; Meyer, Wilfried

    2011-02-01

    The aim of the investigation was to demonstrate that the esophageal epithelium of domesticated mammals exhibits characteristic features of innate immunity. The esophageal samples used were obtained immediately after euthanization from seven species of domesticated mammals of three nutrition groups (herbivores: horse, goat, cattle; omnivores: pig, dog, laboratory rat; carnivores: cat). The experimental basis was immunohistochemistry, which was evaluated in a qualitative and statistically relevant semi-quantitative manner. The first part of the study analyzed the influence of different fixation media on the immunohistochemical reactivities. Two formalin-based routine fixation solutions (Bouin's solution, Ca-acetate formalin) were compared with the recently introduced formalin-free HOPE® fixative. In this context, we clearly demonstrated a diminished immunoreactivity for Ca-formol fixed samples; satisfactory results were obtained, particularly, from samples fixed in Bouin's solution. The HOPE® fixation method offers a relatively cheap alternative, as the antibody amounts can be reduced. An application in routine diagnostic is not advisable, because of several variable parameters. It can be concluded that immunohistochemical results have always to be evaluated and discussed in close relation to the fixation medium used. PMID:19850328

  8. 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

  9. [Cell oncogene expression in normal, metaplastic, dysplastic epithelium and squamous cell carcinoma of the uterine cervix].

    PubMed

    Petrov, S V; Mazurenko, N N; Sukhova, N M; Moroz, I P; Katsenel'son, V M; Raĭkhlin, N T; Kiselev, F L

    1994-01-01

    Immunohistochemical analysis of the protein expression c-myc, ets 1, ets 2, TPR-met, c-fos, c-jun, c-ras-pan, p53, yes, src in 79 samples of normal, metaplastic squamous epithelium, intraepithelial and invasive squamous cell carcinoma of uterine cervix was performed using polyclonal rabbit antibodies to the synthetic peptides homologous active areas of corresponding oncoproteins. Higher content of myc, fos, ets2, p53, ras is noted in metaplasia, dysplasia and in tumours as compared to the normal tissues. Protein myc is revealed in the cytoplasm at a grave dysplasia and in the nucleus in the intraepithelial carcinoma: this may serve as a criterion at a differential diagnosis of these conditions. Expression of the oncoproteins fos, ets2, p53, src in the metaplastic squamous cell carcinoma was higher than in the true squamous cell (ectocervical) carcinoma. When compared to the advanced carcinomas, increase of ets2, p53, and at some degree that of myc, the increase is noted in the latter. Invasive carcinoma with a high level of oncoproteins showed a tendency to the synchronization of myc and ras expression. Poor prognosis was associated with a low level (before treatment) of the expression of the majority of the oncoproteins studied. PMID:7848100

  10. The Incidence of Gastro-Esophageal Disease for the Patients with Typical Chest Pain and a Normal Coronary Angiogram

    PubMed Central

    Nam, Chang-Wook; Lee, Young-Soo; Lee, Sang-Hoon; Han, Seong-Wook; Hur, Seung-Ho; Kim, Yoon-Nyun; Kim, Kwon-Bae; Jang, Byoung-Kuk

    2006-01-01

    Background Although patients may present with typical chest pain and exhibit ischemic changes on the cardiac stress test, they are frequently found to have a normal coronary angiogram. Thus, we wanted to determine which procedures should be performed in order to make an adequate diagnosis of the cause of chest pain. Methods 121 patients (males: 42, 34.7%) who had a normal coronary angiogram with typical chest pain were included in this study. All the patients underwent upper endoscopy, Bernstein's test and esophageal manometry. Results Among the 121 patients, clinically stable angina was noted in 107 (88.4%). Stress testing was done in 82 (67.8%); it was positive in 52 (63.4%). Endoscopic findings were erosive gastritis in 18 (14.8%), gastric ulcer in 4 (3.3%), duodenal ulcer in 5 (4.1%), and reflux esophagitis in 16 (13.2%). Positive results were observed on Berstein's test for 68 patients (56.2%); 59 (86.8%) of them had non-erosive reflux disease. On the esophageal manometry, 35 (28.9%) of these patients had motility disorders. Nutcracker esophagus was observed in 27 patients (22.3%), nonspecific esophageal motility disorder was observed in 5 (4.1%), and hypertensive lower esophageal sphincter was observed in 3 (2.5%). Among the 52 patients with positive cardiac stress testing and a negative coronary angiogram (this clinically corresponded to microvascular angina), 46 patients (85.1%) showed abnormal findings on the gastro-esophageal studies. Conclusions In our study, 85.1% of the patients with microvascular angina revealed positive results of gastric or esophageal disease. In spite of any existing evidence of microvascular angina or cardiac syndrome X, it would be more advisable to perform gastro-esophageal studies to adequately manage chest pain. PMID:16913437

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

    PubMed Central

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

    2015-01-01

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

  12. Different expression of calgizzarin (S100A11) in normal colonic epithelium, adenoma and colorectal carcinoma.

    PubMed

    Melle, Christian; Ernst, Günther; Schimmel, Bettina; Bleul, Annett; Mothes, Henning; Kaufmann, Roland; Settmacher, Utz; Von Eggeling, Ferdinand

    2006-01-01

    The aim of the study was to detect proteomic markers usable to distinguish colorectal carcinoma from colon adenoma for a better understanding of the molecular mechanisms in the process of tumourigenesis. Therefore, we microdissected colon carcinoma tissue, epithelial colon adenoma tissue as well as normal adjacent colon epithelium and determined protein profiles by SELDI-TOF MS. A multitude of significantly different signals was detected. For their identification colon biopsis were lysed and subjected to a two-dimensional gel electrophoresis for separation. Subsequently, we identified nearly 100 proteins by tryptic digestion, peptide fingerprint mapping and database search. Calgizzarin (S100A11; S100C) identified by peptide fingerprint mapping correlated very well with a significantly differentially expressed signal found in prior protein profiling. Using an immunodepletion assay we confirmed the identity of this signal as calgizzarin. To localise calgizzarin in tissues we performed immunohistochemistry. For further confirmation of the identity of calgizzarin we re-analysed IHC-positive as well as IHC-negative tissue sections on ProteinChip arrays. This work demonstrates that biomarkers in colorectal cancer can be detected, identified and assessed by a proteomic approach comprising tissue-microdissection, protein profiling and immunological techniques. PMID:16327996

  13. Immunolocalization of NLRP3 Inflammasome in Normal Murine Airway Epithelium and Changes following Induction of Ovalbumin-Induced Airway Inflammation.

    PubMed

    Tran, Hai B; Lewis, Martin D; Tan, Lor Wai; Lester, Susan E; Baker, Leonie M; Ng, Jia; Hamilton-Bruce, Monica A; Hill, Catherine L; Koblar, Simon A; Rischmueller, Maureen; Ruffin, Richard E; Wormald, Peter J; Zalewski, Peter D; Lang, Carol J

    2012-01-01

    Little is known about innate immunity and components of inflammasomes in airway epithelium. This study evaluated immunohistological evidence for NLRP3 inflammasomes in normal and inflamed murine (Balb/c) airway epithelium in a model of ovalbumin (OVA) induced allergic airway inflammation. The airway epithelium of control mice exhibited strong cytoplasmic staining for total caspase-1, ASC, and NLRP3, whereas the OVA mice exhibited strong staining for active caspase-1, with redistribution of caspase-1, IL-1β and IL-18, indicating possible activation of the NLRP3 inflammasome. Active caspase-1, NLRP3, and other inflammasome components were also detected in tissue eosinophils from OVA mice, and may potentially contribute to IL-1β and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1β and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1β and TNFα. In cultured normal human bronchial epithelial cells, LPS priming resulted in a significant increase in NLRP3 and II-lp protein expression. This study is the first to demonstrate NLRP3 inflammasome components in normal airway epithelium and changes with inflammation. We propose activation and/or luminal release of the inflammasome is a feature of allergic airway inflammation which may contribute to disease pathogenesis. PMID:22523501

  14. 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.

  15. Esophageal blood flow in the cat. Normal distribution and effects of acid perfusion

    SciTech Connect

    Hollwarth, M.E.; Smith, M.; Kvietys, P.R.; Granger, D.N.

    1986-03-01

    The radioactive microsphere technique was used to estimate blood flow to different regions of the esophagus and to adjacent regions of the stomach before and after perfusion of the esophagus with hydrochloric acid (pH 1.5) for 5 min. Under resting conditions total blood flow, as well as blood flow to the mucosal-submucosal layer and the muscular layer, to both sphincters was significantly higher than to the esophageal body. Blood flow to the adjacent regions of the stomach was significantly higher than esophageal blood flow. Acid perfusion resulted in a large increase in total blood flow in both sphincters and the lower esophageal body. Gastric blood flow was not altered by acid perfusion. The esophageal hyperemia resulted primarily from an increase in blood flow to the muscular layer; mucosal-submucosal blood flow was increased only in the lower esophageal sphincter. The present study indicates that short periods (5 min) of gastroesophageal reflux may increase esophageal blood flow.

  16. Effects of Platinum Nanocolloid in Combination with Gamma Irradiation on Normal Human Esophageal Epithelial Cells.

    PubMed

    Li, Qiang; Tanaka, Yoshiharu; Saitoh, Yasukazu; Miwa, Nobuhiko

    2016-05-01

    Our previous study demonstrated that platinum nanocolloid (Pt-nc), combined with lower-dose gamma irradiation at 3, 5, and 7 Gy significantly decreased proliferation and accelerated apoptosis of the human esophageal squamous cell carcinoma-derived cell line KYSE-70. The aim of the present study was to determine, under the same conditions as our previous study where gamma rays combined with Pt-nc were carcinostatic to KYSE-70 cells, if we could induce a radioprotective or the radiation-sensitizing effect on the human normal esophageal epithelial cells (HEEpiC). HEEpiC were treated with various Pt-nc concentrations and then irradiated with various gamma-ray doses. The proliferative status of HEEpiC was evaluated using trypan blue dye-exclusion and WST-8 assays. The cellular and nucleic morphological features were determined using crystal violet and Hoechst 33342 stainings, respectively. The intracellular level of reactive oxygen species (ROS) in HEEpiC was evaluated with a nitro blue tetrazolium (NBT) assay. The apoptotic status was detected with caspase-3, Bax, and Bcl-2 by Western blotting. Either Pt-nc or gamma irradiation could inhibit the growth of HEEpiC; however, their combined use exerted a significant proliferation-inhibitory effect in a Pt-nc dose-dependent manner than gamma irradiation alone. Pt-nc resulted in radiation sensitization rather than radiation protection on HEEpiC in vitro similar to KYSE-70 cells, when Pt-nc was administrated alone or combined with gamma irradiation. Thus, Pt-nc has an inhibitory effect on cell proliferation, a facilitative effect on apoptosis, and a certain degree of toxicity against HEEpiC. PMID:27483929

  17. Quantitative assessment of normal and potentially premalignant epithelium at different levels of human colorectal crypts.

    PubMed

    Tipoe, G L; White, F H

    1998-04-01

    The present study uses morphometric techniques to assess whether altered differentiation patterns exist in PPM which might reflect its premalignant status. Samples were obtained from resected malignant lesions of large bowels of 10 Chinese patients. Normal (N) samples were biopsied from the margins of each resected large bowel. Potentially premalignant (PPM) mucosae were obtained from within 2 cm of the margins of the malignant lesions. Tissues were processed for histological examination and using strict criteria, colorectal crypts were divided into basal (B), intermediate (I) and surface (S) segments. Interactive digitisation of sections from each group was used to generate the following morphometric parameters in each segment: nuclear profile circularity indices (NSF and NCI); nuclear numerical density (NA and NV); the degree of deviation of the major nuclear axis in relation to the epithelial-connective junction (AGDMAX); cell height (CH); the distance between nuclear apex to cell apex (DNACA); the distance between cell base to nuclear apex (DCBNA); stratification index (SI)--the ratio of DCBNA and CH; and the volume density of mucous vacuoles in the reference epithelium (VVMV,EP). In comparisons of different segments within groups, the nuclei at the S segment of N and PPM crypts were more irregular and less circular in shape than nuclei from other segments. There was a shift of nuclear profile shape (NSF and NCI) from circular to ellipsiodal between B and S segments. In comparisons of similar segments between groups, no significant nuclear shape changes were detected in nuclei of PPM crypts when compared with nuclei in similar segments of N crypts and the pattern of nuclear shape alterations resembled those of normal crypts. In comparisons of different segments within groups of N and PPM crypts, AGDMAX, DNACA, DCBNA, CH and SI parameters demonstrated that epithelial cells at the I segments have more centrally positioned nuclei with the tallest epithelial height

  18. Somatically Acquired LINE-1 Insertions in Normal Esophagus Undergo Clonal Expansion in Esophageal Squamous Cell Carcinoma.

    PubMed

    Doucet-O'Hare, Tara T; Sharma, Reema; Rodić, Nemanja; Anders, Robert A; Burns, Kathleen H; Kazazian, Haig H

    2016-09-01

    Squamous cell carcinoma of the esophagus (SCC) is the most common form of esophageal cancer in the world and is typically diagnosed at an advanced stage when successful treatment is challenging. Understanding the mutational profile of this cancer may identify new treatment strategies. Because somatic retrotransposition has been shown in tumors of the gastrointestinal system, we focused on LINE-1 (L1) mobilization as a source of genetic instability in this cancer. We hypothesized that retrotransposition is ongoing in SCC patients. The expression of L1 encoded proteins is necessary for retrotransposition to occur; therefore, we evaluated the expression of L1 open reading frame 1 protein (ORF1p). Using immunohistochemistry, we detected ORF1p expression in all four SCC cases evaluated. Using L1-seq, we identified and validated 74 somatic insertions in eight tumors of the nine evaluated. Of these, 12 insertions appeared to be somatic, not genetically inherited, and sub-clonal (i.e., present in less than one copy per genome equivalent) in the adjacent normal esophagus (NE), while clonal in the tumor. Our results indicate that L1 retrotransposition is active in SCC of the esophagus and that insertion events are present in histologically NE that expands clonally in the subsequent tumor. PMID:27319353

  19. Short segments of Barrett's epithelium and intestinal metaplasia in normal appearing oesophagogastric junctions: the same or two different entities?

    PubMed Central

    Pereira, A; Suspiro, A; Chaves, P; Saraiva, A; Gloria, L; d Mendes; Leitao, C; Soares, J; Mira, F

    1998-01-01

    Background—Endoscopic diagnosis of short segments of Barrett's epithelium (SSBE) is difficult and its meaning in terms of the presence of specialised columnar epithelium (SCE) has not been prospectively evaluated. 
Aims—To evaluate the prevalence of SCE in patients with an endoscopic diagnosis of SSBE and in individuals with normal appearing oesophagogastric junctions, and to compare the clinical characteristics of these two groups. 
Patients—Thirty one patients with an endoscopic diagnosis of short Barrett's oesophagus, less than 3 cm in length (group A), and 44 consecutive patients with normal appearing oesophagogastric junctions (group B). 
Methods—Multiple biopsies were performed in suspicious epithelium and at the oesophagogastric junction in groups A and B, respectively. 
Results—Age and sex distribution were similar in both groups. Reflux symptoms were more frequent in group A (p<0.001), as were endoscopic and histological signs of oesophagitis (p<0.0001 and p=0.001, respectively). SCE was found in 61.3% of group A patients compared with 25% in group B (p<0.002), with men predominating in group A while women were more frequent in group B (p=0.02). The differences in reflux symptoms and endoscopic/histological oesophagitis remained significant. 
Conclusions—These results show that endoscopic diagnosis of SSBE is associated with a high prevalence of SCE, significantly higher than that found in normal appearing oesophagogastric junctions. Differences between patients with SCE in the two groups suggest they may represent two different entities. 

 Keywords: Barrett oesophagus; short segments; endoscopic diagnosis PMID:9659160

  20. Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects

    PubMed Central

    Lee, Robert H; Korsapati, Hariprasad; Bhalla, Vikas; Varki, Nissi; Mittal, Ravinder K

    2016-01-01

    Background/Aims Transient receptor potential vanilloid-1 (TRPV1) is a candidate for mediating acid-induced symptoms in the esophagus. We conducted studies to determine if the presence of acid in the mucosa/submucosa and direct activation of TRPV1 by capsaicin elicited symptoms in normal healthy subjects. We also studied the presence of TRPV1 receptors in the esophagus. Methods Unsedated endoscopy was performed on healthy subjects with no symptoms. Using a sclerotherapy needle, normal saline (pH 2.0–7.5) was injected into the mucosa/submucosa, 5 cm above the Z line. In a separate group of healthy subjects, injection of capsaicin and vehicle was also studied. Quality of symptoms was reported using the McGill Pain Questionnaire, and symptom intensity using the visual analogue scale (VAS). Immunohistochemistry was performed on 8 surgical esophagus specimens using TRPV1 antibody. Results Acid injection either did not elicit or elicited mild symptoms in subjects at all pH solutions. Capsaicin but not the vehicle elicited severe heartburn/chest pain in all subjects. Mean VAS for capsaicin was 91 ± 3 and symptoms lasted for 25 ± 1 minutes. Immunohistochemistry revealed a linear TRPV1 staining pattern between the epithelial layer and the submucosa that extended into the papillae. Eighty-five percent of papillae stained positive for TRPV1 with a mean 1.1 positive papillae per high-powered field. Conclusions The mechanism of acid-induced heartburn and chest pain is not the simple interaction of hydrogen ions with afferents located in the esophageal mucosa and submucosa. TRPV1 receptors are present in the lamina propria and their activation induces heartburn and chest pain. PMID:26932896

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Prytherch, Zoë C; BéruBé, 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

  3. 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, Céline; Gondouin, Pauline; Bigot, Karine; Viénot, Françoise; Gutman, Emmanuel; Fontaine, Valérie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, José-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

  4. 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

  5. Production, Characterization and Potential Uses of a 3D Tissue-engineered Human Esophageal Mucosal Model.

    PubMed

    Green, Nicola H; Corfe, Bernard M; Bury, Jonathan P; MacNeil, Sheila

    2015-01-01

    The incidence of both esophageal adenocarcinoma and its precursor, Barrett's Metaplasia, are rising rapidly in the western world. Furthermore esophageal adenocarcinoma generally has a poor prognosis, with little improvement in survival rates in recent years. These are difficult conditions to study and there has been a lack of suitable experimental platforms to investigate disorders of the esophageal mucosa. A model of the human esophageal mucosa has been developed in the MacNeil laboratory which, unlike conventional 2D cell culture systems, recapitulates the cell-cell and cell-matrix interactions present in vivo and produces a mature, stratified epithelium similar to that of the normal human esophagus. Briefly, the model utilizes non-transformed normal primary human esophageal fibroblasts and epithelial cells grown within a porcine-derived acellular esophageal scaffold. Immunohistochemical characterization of this model by CK4, CK14, Ki67 and involucrin staining demonstrates appropriate recapitulation of the histology of the normal human esophageal mucosa. This model provides a robust, biologically relevant experimental model of the human esophageal mucosa. It can easily be manipulated to investigate a number of research questions including the effectiveness of pharmacological agents and the impact of exposure to environmental factors such as alcohol, toxins, high temperature or gastro-esophageal refluxate components. The model also facilitates extended culture periods not achievable with conventional 2D cell culture, enabling, inter alia, the study of the impact of repeated exposure of a mature epithelium to the agent of interest for up to 20 days. Furthermore, a variety of cell lines, such as those derived from esophageal tumors or Barrett's Metaplasia, can be incorporated into the model to investigate processes such as tumor invasion and drug responsiveness in a more biologically relevant environment. PMID:26067284

  6. Infrared spectroscopy characterization of normal and lung cancer cells originated from epithelium

    PubMed Central

    Lee, So Yeong; Yoon, Kyong-Ah; Jang, Soo Hwa; Ganbold, Erdene Ochir; Uuriintuya, Dembereldorj; Shin, Sang-Mo; Ryu, Pan Dong

    2009-01-01

    The vibrational spectral differences of normal and lung cancer cells were studied for the development of effective cancer cell screening by means of attenuated total reflection infrared spectroscopy. The phosphate monoester symmetric stretching νs(PO32-) band intensity at ~970 cm-1 and the phosphodiester symmetric stretching νs(PO2-) band intensity at ~1,085 cm-1 in nucleic acids and phospholipids appeared to be significantly strengthened in lung cancer cells with respect to the other vibrational bands compared to normal cells. This finding suggests that more extensive phosphorylation occur in cancer cells. These results demonstrate that lung cancer cells may be prescreened using infrared spectroscopy tools. PMID:19934594

  7. 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.

  8. Widespread expression of serum amyloid A in histologically normal human tissues. Predominant localization to the epithelium.

    PubMed

    Urieli-Shoval, S; Cohen, P; Eisenberg, S; Matzner, Y

    1998-12-01

    Serum amyloid A (SAA) is an acute-phase reactant whose level in the blood is elevated to 1000-fold as part of the body's responses to various injuries, including trauma, infection, inflammation, and neoplasia. As an acute-phase reactant, the liver has been considered to be the primary site of expression. However, limited extrahepatic SAA expression was described in mouse tissues and in cells of human atherosclerotic lesions. Here we describe nonradioactive in situ hybridization experiments revealing that the SAA mRNA is widely expressed in many histologically normal human tissues. Expression was localized predominantly to the epithelial components of a variety of tissues, including breast, stomach, small and large intestine, prostate, lung, pancreas, kidney, tonsil, thyroid, pituitary, placenta, skin epidermis, and brain neurons. Expression was also observed in lymphocytes, plasma cells, and endothelial cells. RT-PCR analysis of selected tissues revealed expression of the SAA1, SAA2, and SAA4 genes but not of SAA3, consistent with expression of these genes in the liver. Immunohistochemical staining revealed SAA protein expression that co-localized with SAA mRNA expression. These data indicate local production of the SAA proteins in histologically normal human extrahepatic tissues. PMID:9815279

  9. Apical Secretion of FSTL1 in the Respiratory Epithelium for Normal Lung Development

    PubMed Central

    Li, Xue; Liang, Jiurong; Jiang, Dianhua; Geng, Yan; Ning, Wen

    2016-01-01

    Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC-Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function. Moreover, we found that FSTL1 function was blocked by the epithelial polarization, which was reflected by the remarkable apical secretion of FSTL1 and the basolateral BMP signaling. Taken together, this study demonstrates that tightly spatial interaction of FSTL1 and BMP signaling plays an essential role in lung development. PMID:27355685

  10. Apical Secretion of FSTL1 in the Respiratory Epithelium for Normal Lung Development.

    PubMed

    Li, Xiaohe; Fang, Yinshan; Li, Xue; Liang, Jiurong; Jiang, Dianhua; Geng, Yan; Ning, Wen

    2016-01-01

    Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC-Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function. Moreover, we found that FSTL1 function was blocked by the epithelial polarization, which was reflected by the remarkable apical secretion of FSTL1 and the basolateral BMP signaling. Taken together, this study demonstrates that tightly spatial interaction of FSTL1 and BMP signaling plays an essential role in lung development. PMID:27355685

  11. Comparative gene expression analysis of ovarian carcinoma and normal ovarian epithelium by serial analysis of gene expression.

    PubMed

    Peters, David G; Kudla, Donna M; Deloia, Julie A; Chu, Tian Jiao; Fairfull, Liane; Edwards, Robert P; Ferrell, Robert E

    2005-07-01

    Despite the poor prognosis of ovarian cancer and the importance of early diagnosis, there are no reliable noninvasive biomarkers for detection in the early stages of disease. Therefore, to identify novel ovarian cancer markers with potential utility in early-stage screening protocols, we have undertaken an unbiased and comprehensive analysis of gene expression in primary ovarian tumors and normal human ovarian surface epithelium (HOSE) using Serial Analysis of Gene Expression (SAGE). Specifically, we have generated SAGE libraries from three serous adenocarcinomas of the ovary and, using novel statistical tools, have compared these to SAGE data derived from two pools of normal HOSE. Significantly, in contrast to previous SAGE-based studies, our normal SAGE libraries are not derived from cultured cell lines. We have also compared our data with publicly available SAGE data obtained from primary tumors and "normal" HOSE-derived cell lines. We have thus identified several known and novel genes whose expressions are elevated in ovarian cancer. These include but are not limited to CLDN3, WFDC2, FOLR1, COL18A1, CCND1, and FLJ12988. Furthermore, we found marked differences in gene expression patterns in primary HOSE tissue compared with cultured HOSE. The use of HOSE tissue as a control for these experiments, along with hierarchical clustering analysis, identified several potentially novel biomarkers of ovarian cancer, including TACC3, CD9, GNAI2, AHCY, CCT3, and HMGA1. In summary, these data identify several genes whose elevated expressions have not been observed previously in ovarian cancer, confirm the validity of several existing markers, and provide a foundation for future studies in the understanding and management of this disease. PMID:16030107

  12. Detection of molecular signatures of oral squamous cell carcinoma and normal epithelium - application of a novel methodology for unsupervised segmentation of imaging mass spectrometry data.

    PubMed

    Widlak, Piotr; Mrukwa, Grzegorz; Kalinowska, Magdalena; Pietrowska, Monika; Chekan, Mykola; Wierzgon, Janusz; Gawin, Marta; Drazek, Grzegorz; Polanska, Joanna

    2016-06-01

    Intra-tumor heterogeneity is a vivid problem of molecular oncology that could be addressed by imaging mass spectrometry. Here we aimed to assess molecular heterogeneity of oral squamous cell carcinoma and to detect signatures discriminating normal and cancerous epithelium. Tryptic peptides were analyzed by MALDI-IMS in tissue specimens from five patients with oral cancer. Novel algorithm of IMS data analysis was developed and implemented, which included Gaussian mixture modeling for detection of spectral components and iterative k-means algorithm for unsupervised spectra clustering performed in domain reduced to a subset of the most dispersed components. About 4% of the detected peptides showed significantly different abundances between normal epithelium and tumor, and could be considered as a molecular signature of oral cancer. Moreover, unsupervised clustering revealed two major sub-regions within expert-defined tumor areas. One of them showed molecular similarity with histologically normal epithelium. The other one showed similarity with connective tissue, yet was markedly different from normal epithelium. Pathologist's re-inspection of tissue specimens confirmed distinct features in both tumor sub-regions: foci of actual cancer cells or cancer microenvironment-related cells prevailed in corresponding areas. Hence, molecular differences detected during automated segmentation of IMS data had an apparent reflection in real structures present in tumor. PMID:27168173

  13. 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

  14. 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 α-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

  15. Pattern of antioxidant and DNA repair gene expression in normal airway epithelium associated with lung cancer diagnosis.

    PubMed

    Blomquist, Thomas; Crawford, Erin L; Mullins, D'Anna; Yoon, Youngsook; Hernandez, Dawn-Alita; Khuder, Sadik; Ruppel, Patricia L; Peters, Elizabeth; Oldfield, David J; Austermiller, Brad; Anders, John C; Willey, James C

    2009-11-15

    In previous studies, we reported that key antioxidant and DNA repair genes are regulated differently in normal bronchial epithelial cells of lung cancer cases compared with non-lung cancer controls. In an effort to develop a biomarker for lung cancer risk, we evaluated the transcript expressions of 14 antioxidant, DNA repair, and transcription factor genes in normal bronchial epithelial cells (HUGO names CAT, CEBPG, E2F1, ERCC4, ERCC5, GPX1, GPX3, GSTM3, GSTP1, GSTT1, GSTZ1, MGST1, SOD1, and XRCC1). A test comprising these 14 genes accurately identified the lung cancer cases in two case-control studies. The receiver operating characteristic-area under the curve was 0.82 (95% confidence intervals, 0.68-0.91) for the first case-control set (25 lung cancer cases and 24 controls), and 0.87 (95% confidence intervals, 0.73-0.96) for the second set (18 cases and 22 controls). For each gene included in the test, the key difference between cases and controls was altered distribution of transcript expression among cancer cases compared with controls, with more lung cancer cases expressing at both extremes among all genes (Kolmorogov-Smirnov test, D = 0.0795; P = 0.041). A novel statistical approach was used to identify the lower and upper boundaries of transcript expression that optimally classifies cases and controls for each gene. Based on the data presented here, there is an increased prevalence of lung cancer diagnosis among individuals that express a threshold number of key antioxidant, DNA repair, and transcription factor genes at either very high or very low levels in the normal airway epithelium. PMID:19887610

  16. Expression of Cell Competition Markers at the Interface between p53 Signature and Normal Epithelium in the Human Fallopian Tube

    PubMed Central

    Kito, Masahiko; Maeda, Daichi; Kudo-Asabe, Yukitsugu; Sato, Naoki; Shih, Ie-Ming; Wang, Tian-Li; Tanaka, Masamitsu; Terada, Yukihiro; Goto, Akiteru

    2016-01-01

    There is a growing body of evidence regarding cell competition between normal and mutant mammalian cells, which suggest that it may play a defensive role in the early phase of carcinogenesis. In vitro study in the past has shown that overexpression of vimentin in normal epithelial cells at the contact surface with transformed cells is essential for the cell competition involved in epithelial defense against cancer. In this study, we attempted to examine cell competition in human tissue in vivo by investigating surgically resected human fallopian tubes that contain p53 signatures and serous tubal intraepithelial lesions (STILs), a linear expansion of p53-immunopositive/TP53 mutant tubal epithelial cells that are considered as precursors of pelvic high grade serous carcinoma. Immunofluorescence double staining for p53 and the cell competition marker vimentin was performed in 21 sections of human fallopian tube tissue containing 17 p53 signatures and 4 STILs. The intensities of vimentin expression at the interface between p53-positive cells at the end of the p53 signature/STIL and adjacent p53-negative normal tubal epithelial cells were compared with the background tubal epithelium. As a result, the average vimentin intensity at the interfaces relative to the background intensity was 1.076 (95% CI, 0.9412 – 1.211 for p53 signature and 0.9790 (95% CI, 0.7206 – 1.237) for STIL. Thus, it can be concluded that overexpression of the cell competition marker vimentin are not observed in human tissue with TP53 alterations. PMID:27258067

  17. 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

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

    PubMed Central

    Hirano, Ikuo; Aceves, Seema S.

    2014-01-01

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

  19. N-Ethylmaleimide–Sensitive Factor b (nsfb) Is Required for Normal Pigmentation of the Zebrafish Retinal Pigment Epithelium

    PubMed Central

    Hanovice, Nicholas J.; Daly, Christina M. S.; Gross, Jeffrey M.

    2015-01-01

    Purpose Despite the number of albinism-causing mutations identified in human patients and animal models, there remain a significant number of cases for which no mutation has been identified, suggesting that our understanding of melanogenesis is incomplete. Previously, we identified two oculocutaneous albinism mutations in zebrafish, au13 and au18. Here, we sought to identify the mutated loci and determine how the affected proteins contribute to normal pigmentation of the retinal pigment epithelium (RPE). Methods Complementation analyses revealed that au13 and au18 belonged to a single complementation group, suggesting that they affected the same locus. Whole-genome sequencing and single nucleotide polymorphism (SNP) analysis was performed to identify putative mutations, which were confirmed by cDNA sequencing and mRNA rescue. Transmission electron microscopy (TEM) and image quantification were used to identify the cellular basis of hypopigmentation. Results Whole-genome sequencing and SNP mapping identified a nonsense mutation in the N-ethylmaleimide–sensitive factor b (nsfb) gene in au18 mutants. Complementary DNA sequencing confirmed the presence of the mutation (C893T), which truncates the nsfb protein by roughly two-thirds (Y297X). No coding sequence mutations were identified in au13, but quantitative PCR revealed a significant decrease in nsfb expression, and nsfb mRNA injection rescued the hypopigmentation phenotype, suggesting a regulatory mutation. In situ hybridization revealed that nsfb is broadly expressed during embryonic development, including in the RPE. Transmission electron microscopy analyses indicated that average melanosome density and maturity were significantly decreased in nsfb mutants. Conclusions au18 and au13 contain mutations in nsfb, which encodes a protein that is required for the maturation of melanosomes in zebrafish RPE. PMID:26618645

  20. 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.

  1. 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.

  2. Three-dimensional telomere architecture of esophageal squamous cell carcinoma: comparison of tumor and normal epithelial cells.

    PubMed

    Sunpaweravong, S; Sunpaweravong, P; Sathitruangsak, C; Mai, S

    2016-05-01

    Telomeres are repetitive nucleotide sequences (TTAGGG)n located at the ends of chromosomes that function to preserve chromosomal integrity and prevent terminal end-to-end fusions. Telomere loss or dysfunction results in breakage-bridge-fusion cycles, aneuploidy, gene amplification and chromosomal rearrangements, which can lead to genomic instability and promote carcinogenesis. Evaluating the hypothesis that changes in telomeres contribute to the development of esophageal squamous cell carcinoma (ESCC) and to determine whether there are differences between young and old patients, we compared the three-dimensional (3D) nuclear telomere architecture in ESCC tumor cells with that of normal epithelial cells obtained from the same patient. Patients were equally divided by age into two groups, one comprising those less than 45 years of age and the other consisting of those over 80 years of age. Tumor and normal epithelial cells located at least 10 cm from the border of the tumor were biopsied in ESCC patients. Hematoxylin and eosin staining was performed for each sample to confirm and identify the cancer and normal epithelial cells. This study was based on quantitative 3D fluorescence in situ hybridization (Q-FISH), 3D imaging and 3D analysis of paraffin-embedded slides. The 3D telomere architecture data were computer analyzed using 100 nuclei per slide. The following were the main parameters compared: the number of signals (number of telomeres), signal intensity (telomere length), number of telomere aggregates, and nuclear volume. Tumor and normal epithelial samples from 16 patients were compared. The normal epithelial cells had more telomere signals and higher intensities than the tumor cells, with P-values of P < 0.0001 and P = 0.0078, respectively. There were no statistically significant differences in the numbers of telomere aggregates or the nuclear volumes between the tumor and normal epithelial cells. Secondary analyses examined the effects of age on 3D telomere

  3. Intraepithelial p63-dependent expression of distinct components of cell adhesion complexes in normal esophageal mucosa and squamous cell carcinoma.

    PubMed

    Thépot, Amélie; Hautefeuille, Agnès; Cros, Marie-Pierre; Abedi-Ardekani, Behnoush; Pétré, Aurélia; Damour, Odile; Krutovskikh, Vladimir; Hainaut, Pierre

    2010-11-01

    TP63 gene is a member of TP53 tumor suppressor gene family that encodes several protein isoforms involved in the process of epithelial stratification and in epithelial-mesenchyme interactions. TP63 is amplified in a significant proportion of squamous cell carcinoma of the esophagus (ESCC), resulting in the hyper-expression of DeltaNp63 as the major p63 isoform. To better understand the contribution of this high expression to tumorigenesis, we have analyzed the impact of intraepithelial p63 expression on the expression of cell adhesion complexes in normal esophagus and in ESCC cell lines. Cells expressing p63 showed an adhesion pattern characterized by lack of tight junctions and presence of adherens junctions. Cell differentiation was accompanied by a decrease in p63 and by a shift to adhesion patterns involving tight junctions. Silencing of p63 mRNA in ESCC cell lines resulted in a similar shift, characterized by increased expression of component of tight junctions, decreased cell-to-cell communication and downregulation of cell proliferation. These results indicate that DeltaNp63 may contribute to esophageal squamous carcinogenesis by maintaining cell adhesion patterns compatible with cell proliferation. PMID:20127860

  4. Intrinsic resistance triggered under acid loading within normal esophageal epithelial cells: NHE1- and ROS-mediated survival.

    PubMed

    Park, Sun Young; Lee, Yeon Joo; Cho, Eun Jeong; Shin, Chang Yell; Sohn, Uy Dong

    2015-07-01

    The transition to a pathological phenotype such as Barrett's esophagus occurs via induction of resistance upon repeated contact with gastric refluxate in esophagus. This study examined the molecular changes within normal esophageal epithelial cells (EECs) under short-term acid loading and the role of these changes in defensive resistance against acidic cytotoxicity. After primary cultured EECs were exposed to pH 4-acidified medium (AM4), cell viability was determined by the MTT assay. Reactive oxygen species (ROS) and NAD(P)H oxidase (NOX) activity were measured. Activation of the mitogen-activated protein kinases (MAPKs) MEK/ERK1/2, p38 and JNK; phosphoinositol-3-kinase (PI3K)/Akt, and nuclear factor-kappa B (NF-κB) were detected by Western blot analysis or immunofluorescence staining. AM4 incubation induced intracellular ROS generation accompanied by increase in NOX activity, which was further increased by Na(+) /H(+) exchange-1 (NHE1)-dependent inhibition but was prevented by inhibition of NOX or mitochondria complex I. AM4 also induced phosphorylation of MEK/ERK1/2, p38 MAPK, PI3K/Akt, and nuclear translocation of NF-κB, and all these effects, except for p38 MAPK phosphorylation, were abolished by inhibition of ROS. ROS-dependent PI3K/Akt activation, which mediates NF-κB nuclear translocation, was inhibited by protein tyrosine kinase (PTK) inhibitors and NHE1-specific inhibitor. All inhibitors of NHE, ROS, PTK, PI3K, or NF-κB further decreased AM4-induced cell viability. Acid loading in the presence of NHE1-dependent protection induced ROS generation by activating NOX and mitochondria complex I, which stimulated PTK/PI3K/Akt/NF-κB-dependent survival in EEC. Our data indicate that normal EEC initially respond to acid loading through intrinsic survival activation. PMID:25522216

  5. Studies on the Thomsen-Friedenreich antigen in human colon with the lectin Amaranthin. Normal and neoplastic epithelium express only cryptic T antigen.

    PubMed

    Sata, T; Roth, J; Zuber, C; Stamm, B; Rinderle, S J; Goldstein, I J; Heitz, P U

    1992-02-01

    The lectin Amaranthin has been shown to be highly specific for the galactose beta 1,3 N-acetylgalactosamine-alpha and sialic acid alpha 2,3 galactose beta 1,3 N-acetylgalactosamine-alpha sequence which represents the Thomsen-Friedenreich (T) antigen and its cryptic form, respectively. Previously, we demonstrated the usefulness of gold-labeled Amaranthin for the histochemical detection of the T antigen and its cryptic form. Application of the galactose oxidase (GO)-Schiff sequence abolished lectin binding to the T antigen but not its cryptic form, and therefore permitted their differentiation. In the present study we have analyzed by light and electron microscopy the distribution and subcellular localization of Amaranthin binding sites in normal, dysplastic and neoplastic colonic epithelium. Furthermore, a monoclonal antibody raised against synthetic galactose bera 1,3 N-acetylgalactosamine-alpha-bovine serum albumin was applied as a reagent for the T antigen. In normal colonic mucosa, two different Amaranthin staining patterns existed: (a) reactivity restricted to the lower portion of the crypts which was principally observed in the left colon, and (b) reactivity along the entire length of the crypts and in the surface epithelium with goblet cell staining in the upper portion of the crypts which was principally observed in the right colon. This Amaranthin staining was resistant to GO-Schiff treatment. No immunostaining with the monoclonal anti-T antigen was observed. Investigation of transitional mucosa, adenocarcinomas of different degrees of differentiation and mucinous carcinomas as well as adenomas with different degrees of dysplasia all revealed positive Amaranthin staining. The lectin staining was resistant to GO-Schiff treatment, and immunolabeling with the monoclonal antibody against the T antigen was absent. These results indicate that only the cryptic form of the T antigen is expressed in normal, dysplastic and neoplastic human colonic epithelium. PMID

  6. Salvage endoscopic resection as a treatment for locoregional failure or recurrence following chemoradiotherapy or radiotherapy for esophageal cancer

    PubMed Central

    NAKAMURA, RIEKO; OMORI, TAI; TAKEUCHI, HIROYA; KAWAKUBO, HIROFUMI; TAKAHASHI, TSUNEHIRO; WADA, NORIHITO; SAIKAWA, YOSHIRO; KITAGAWA, YUKO

    2016-01-01

    Radiotherapy (RT) or chemoradiotherapy (CRT) is a potentially curative, non-surgical treatment option for esophageal cancer, although the rate of local failure within the esophagus remains relatively high. Salvage esophagectomy is not regarded as a common treatment for esophageal cancer, since it is a high-risk surgery with a relatively high surgical mortality rate. Salvage endoscopic resection (ER) for local failure is used for treatment when esophageal cancer is localized and superficial. To evaluate to usefulness of salvage ER, the present study reviewed the clinicopathological records and follow-up data of 37 patients that underwent salvage ER for esophageal cancer, following initial treatment with RT or CRT. Salvage ER was conducted on a total of 78 lesions observed in the 37 patients. Since a thick epithelium and lack of normal vessels on the surface of the mucosa are characteristics of esophageal mucosa following RT or CRT, almost all the lesions were detected using iodine dyeing, and not by narrow band imaging. The growth rate of the detected lesions was relatively high, and early treatment was required. No particular complications occurred during the endoscopic treatment. A total of 11 patients survived for >5 years subsequent to initial endoscopic treatment. Only 4 patients succumbed to esophageal cancer. In conclusion, the present study demonstrated that salvage ER following CRT or RT for esophageal cancer is a minimally invasive, safe, adaptive and curative method for superficial lesions without distant metastases in patients with esophageal cancer with local failure following CRT or RT. PMID:27284365

  7. Normal values of 24-hour ambulatory esophageal impedance-pH monitoring in a rural South African cohort of healthy participants.

    PubMed

    Ndebia, E J; Sammon, A M; Umapathy, E; Iputo, J E

    2016-05-01

    There are no data on 24-hour multichannel intraluminal impedance and pH monitoring in African populations. The purpose of this study was to provide the normal values of esophageal impedance and pH monitoring in a rural African populations. South African healthy rural participants were recruited and underwent 24 hours of esophageal impedance and pH monitoring. The median and the 95th percentiles of the total reflux episodes were 49 and 97, respectively, of which the corresponding number of acidic, weakly acidic, and weakly alkaline reflux were 15 and 55, 17 and 51, and 8 and 36, respectively. The compositions of the total reflux were 5 and 21 for liquid, 27 and 72 for mixed, and 10 and 39 for gas reflux, respectively. The median bolus clearance was 18 seconds and the median bolus exposure was 14 minutes/24 hours. The proximal extent was 6%. The 95th percent time of esophageal exposure to acid was 8.6 in 24 hours. Female and overweight participants were associated with an increased number of reflux events. There were more reflux episodes, and of which, more were weakly alkaline compared with previous similar studies. The findings provide reference values of gastroesophageal reflux for a South African rural population. PMID:25721534

  8. Normal esophageal high-resolution manometry and impedance values in the supine and sitting positions in the population of Northern China.

    PubMed

    Gao, F; Gao, Y; Hobson, A R; Huang, W N; Shang, Z M

    2016-04-01

    The aim of this study was to investigate the normal high-resolution manometry and impedance (HRiM) values in the supine and sitting positions in the population of Northern China, and to investigate the influence of different body positions and bolus consistency on esophageal HRiM findings. In this study, healthy volunteers in the supine position underwent esophageal HRiM examination of 10 swallows of 5 mL normal saline solution and 10 swallows of 5 mL synthetic gel of known viscosity, and in the sitting position of an additional five swallows of a synthetic gel of known viscosity. Total bolus transit time (TBTT), complete bolus transit rate (CBTR), distal contractile integral (DCI), distal esophageal amplitude (DEA), and integrated relaxation pressure (IRP) were measured. Sixty-two healthy volunteers were examined in the supine position and 45 of these performed additional swallows of the viscous gel in the sitting position. In the supine position, normal values for swallowing the liquid and viscous boli were as follows: TBTT 6.9 ± 0.9 and 8.0 ± 1.2 s (P < 0.001), CBTR 90.3 ± 14.0 and 77.9 ± 20.3% (P < 0.001), DCI 1891.5 ± 1131.9 and 1967.8 ± 1140.1 mmHg.s.cm (P = 0.227), DEA 95.3 ± 35.4 and 98.7 ± 37.5 mmHg (P = 0.148), and IRP 10.4 ± 4.9 and 9.0 ± 4.2 mmHg (P < 0.001), respectively. For swallows of the viscous boli in the sitting position, TBTT, DCI, DEA, and IRP were significantly decreased, while CBTR was unchanged (P = 0.075). Normal HRiM values of the population of Northern China were established. Esophageal transit times of viscous boli were significantly slower, more often incomplete and produced less normal peristalsis in the supine position than swallows of liquid boli. Independent reference values for different manometric systems, body positions, and population need to be established before clinical application. PMID:25516299

  9. 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

  10. Esophageal anastomosis - how the granulation phase of wound healing improves the incidence of anastomotic leakage

    PubMed Central

    Tabola, Renata; Augoff, Katarzyna; Lewandowski, Andrzej; Ziolkowski, Piotr; Szelachowski, Piotr; Grabowski, Krzysztof

    2016-01-01

    A two-stage esophagectomy with an interval for reconstruction of the esophagus creates an opportunity for the esophageal stump to recover from vessel injury and allows the formation of granulation tissue rich in proangiogenic factors, including transforming growth factor β (TGF-β) and vascular endothelial growth factor A (VEGF-A), which may have an impact on anastomosis healing. The present study comprised 25 patients (27 in total, 2 succumbed to complications following surgery) who underwent two-stage esophagectomy for squamous cell carcinoma in the Department of Gastrointestinal and General Surgery, Wrocław Medical University (Wrocław, Poland) between January 2007 and December 2012. Immunohistochemical staining for VEGF-A and TGF-β was performed to evaluate esophageal wall specimens at the time of esophagostomy construction and prior to anastomosis, in which the cervical esophagus was connected with the colon or ileum. At the time of reconstructive surgery, a significant increase in microvessel density was observed in all esophageal specimens (P<0.03). Significant differences were also identified in the immunohistochemical staining intensity of TGF-β and VEGF-A in the epithelium of all esophageal specimens between biopsies obtained from normal esophageal tissues at the time of esophagectomy and during reconstructive surgery. Delayed anastomosis construction provides an advantage for the esophageal stump to accumulate proangiogenic growth factors, which overlap with the subsequent proliferative stage of the anastomosed tissue and thus supports its recovery, creating an optimal environment for the healing of any fistulas. PMID:27602135

  11. 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

  12. 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 ...

  13. Esophageal Cancer

    MedlinePlus

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

  14. 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 ...

  15. CIP2A expression and prognostic role in patients with esophageal adenocarcinoma.

    PubMed

    Rantanen, Tuomo; Kauttu, Tuuli; Åkerla, Jonne; Honkanen, Teemu; Krogerus, Leena; Salo, Jarmo; Paavonen, Timo; Oksala, Niku

    2013-01-01

    CIP2A is overexpressed in many cancers, including esophageal squamous cell carcinoma. The regulation of c-MYC and CIP2A expression is characterized by a positive feedback mechanism facilitating the expression of both of them and accelerating cancer cell proliferation in gastric cancer. Increased CIP2A expression is a predictor of poor survival in some cancers. The incidence of positive CIP2A immunostaining and its association with c-MYC and its predictive value in esophageal adenocarcinoma are unknown. All esophageal adenocarcinoma patients from 1990 to 2007 with sufficient material for analysis of CIP2A and c-MYC in two university hospitals were included in the study. In addition, biopsies from Barrett's epithelium from the cancer patients and control tissue from normal esophageal mucosa adjacent to the tumor were included. CIP2A was moderately or strongly positive in 77.9 %, and c-MYC in 93.8 % of the cancer specimens. These frequencies were statistically different from the expression in normal esophageal epithelium. In addition, there was a positive correlation between CIP2A and c-MYC expression (p = 0.018). According to adjusted Cox regression survival analysis, CIP2A and c-MYC had no effect on survival. However, among patients with stage IVA-IVB cancer, there was a trend toward poor prognosis in CIP2A-positive patients. The expression of CIP2A and c-MYC was associated with each other, and their overexpression was found in most cases of esophageal adenocarcinoma. However, CIP2A and c-MYC had no effect on survival. PMID:23925667

  16. Understanding the sensory irregularities of esophageal disease.

    PubMed

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

    2016-08-01

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

  17. 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

  18. Growth Hormone Is Secreted by Normal Breast Epithelium upon Progesterone Stimulation and Increases Proliferation of Stem/Progenitor Cells

    PubMed Central

    Lombardi, Sara; Honeth, Gabriella; Ginestier, Christophe; Shinomiya, Ireneusz; Marlow, Rebecca; Buchupalli, Bharath; Gazinska, Patrycja; Brown, John; Catchpole, Steven; Liu, Suling; Barkan, Ariel; Wicha, Max; Purushotham, Anand; Burchell, Joy; Pinder, Sarah; Dontu, Gabriela

    2014-01-01

    Summary Using in vitro and in vivo experimental systems and in situ analysis, we show that growth hormone (GH) is secreted locally by normal human mammary epithelial cells upon progesterone stimulation. GH increases proliferation of a subset of cells that express growth hormone receptor (GHR) and have functional properties of stem and early progenitor cells. In 72% of ductal carcinoma in situ lesions, an expansion of the cell population that expresses GHR was observed, suggesting that GH signaling may contribute to breast cancer development. PMID:24936466

  19. 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 Barrett’s 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

  20. Pigment epithelium-derived factor (PEDF) normalizes matrix defects in iPSCs derived from Osteogenesis imperfecta Type VI.

    PubMed

    Belinsky, Glenn S; Ward, Leanne; Chung, Chuhan

    2016-01-01

    Osteogenesis imperfecta (OI) Type VI is characterized by a defect in bone mineralization, which results in multiple fractures early in life. Null mutations in the PEDF gene, Serpinf1, are the cause of OI VI. Whether PEDF restoration in a murine model of OI Type VI could improve bone mass and function was previously unknown. In Belinsky et al, we provided evidence that PEDF delivery enhanced bone mass and improved parameters of bone function in vivo. Further, we demonstrated that PEDF temporally inhibits Wnt signaling to enhance osteoblast differentiation. Here, we demonstrate that generation of induced pluripotent stem cells (iPSCs) from a PEDF null patient provides additional evidence for PEDF's role in regulating extracellular matrix proteins secreted from osteoblasts. PEDF null iPSCs have marked abnormalities in secreted matrix proteins, capturing a key feature of human OI Type VI, which were normalized by exogenous PEDF. Lastly, we place our recent findings within the broader context of PEDF biology and the developmental signaling pathways that are implicated in its actions. PMID:27579219

  1. Pigment epithelium-derived factor (PEDF) normalizes matrix defects in iPSCs derived from Osteogenesis imperfecta Type VI

    PubMed Central

    Belinsky, Glenn S.; Ward, Leanne; Chung, Chuhan

    2016-01-01

    ABSTRACT Osteogenesis imperfecta (OI) Type VI is characterized by a defect in bone mineralization, which results in multiple fractures early in life. Null mutations in the PEDF gene, Serpinf1, are the cause of OI VI. Whether PEDF restoration in a murine model of OI Type VI could improve bone mass and function was previously unknown. In Belinsky et al, we provided evidence that PEDF delivery enhanced bone mass and improved parameters of bone function in vivo. Further, we demonstrated that PEDF temporally inhibits Wnt signaling to enhance osteoblast differentiation. Here, we demonstrate that generation of induced pluripotent stem cells (iPSCs) from a PEDF null patient provides additional evidence for PEDF's role in regulating extracellular matrix proteins secreted from osteoblasts. PEDF null iPSCs have marked abnormalities in secreted matrix proteins, capturing a key feature of human OI Type VI, which were normalized by exogenous PEDF. Lastly, we place our recent findings within the broader context of PEDF biology and the developmental signaling pathways that are implicated in its actions. PMID:27579219

  2. 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

  3. Eosinophilic esophagitis.

    PubMed

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

    2015-01-01

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

  4. Esophageal Cancer.

    PubMed

    Alsop, Benjamin R; Sharma, Prateek

    2016-09-01

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

  5. Progenitor Epithelium

    PubMed Central

    Marty-Santos, Leilani

    2015-01-01

    Insulin-producing β 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 β 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 β 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 β cells and other pancreatic lineages. PMID:26216134

  6. Esophageal melanocytosis in oral opium consumption.

    PubMed

    Geramizadeh, Bita; Asadian, Fatemeh; Taghavi, Alireza

    2014-01-01

    Esophageal melanocytosis is a rare and benign condition, characterized by melanocytic proliferation of the esophageal squamous epithelium with heavy melanin deposition. The etiology and pathogenesis has not been exactly known but it seems to be a chronic stimulus such as gastroesophageal reflux. This condition is very rare and about 35 cases have been reported so far, most of which have been from India and Japan. Herein, we present a case of esophageal melanocytosis in a patient with long history of oral opium consumption. To the best of our knowledge, such a history has not been reported. PMID:24719715

  7. 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-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE. PMID:24910846

  8. The Pathophysiology of Eosinophilic Esophagitis

    PubMed Central

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

    2014-01-01

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

  9. The Discovery and Validation of Biomarkers for the Diagnosis of Esophageal Squamous Dysplasia and Squamous Cell Carcinoma.

    PubMed

    Couch, George; Redman, James E; Wernisch, Lorenz; Newton, Richard; Malhotra, Shalini; Dawsey, Sanford M; Lao-Sirieix, Pierre; Fitzgerald, Rebecca C

    2016-07-01

    The 5-year survival rate of esophageal cancer is less than 10% in developing countries, where more than 90% of these cancers are esophageal squamous cell carcinomas (ESCC). Endoscopic screening is undertaken in high incidence areas. Biomarker analysis could reduce the subjectivity associated with histologic assessment of dysplasia and thus improve diagnostic accuracy. The aims of this study were therefore to identify biomarkers for esophageal squamous dysplasia and carcinoma. A publicly available dataset was used to identify genes with differential expression in ESCC compared with normal esophagus. Each gene was ranked by a support vector machine separation score. Expression profiles were examined, before validation by qPCR and IHC. We found that 800 genes were overexpressed in ESCC compared with normal esophagus (P < 10(-5)). Of the top 50 genes, 33 were expressed in ESCC epithelium and not in normal esophagus epithelium or stroma using the Protein Atlas website. These were taken to qPCR validation, and 20 genes were significantly overexpressed in ESCC compared with normal esophagus (P < 0.05). TNFAIP3 and CHN1 showed differential expression with IHC. TNFAIP3 expression increased gradually through normal esophagus, mild, moderate and severe dysplasia, and SCC (P < 0.0001). CHN1 staining was rarely present in the top third of normal esophagus epithelium and extended progressively towards the surface in mild, moderate, and severe dysplasia, and SCC (P < 0.0001). Two novel promising biomarkers for ESCC were identified, TNFAIP3 and CHN1. CHN1 and TNFAIP3 may improve diagnostic accuracy of screening methods for ESCC. Cancer Prev Res; 9(7); 558-66. ©2016 AACR. PMID:27072986

  10. Esophageal manometry

    MedlinePlus

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

  11. 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 ...

  12. Esophagitis - infectious

    MedlinePlus

    ... system Organisms (germs) that cause esophagitis include fungi, yeast, and viruses. Common organisms include: Candida albicans Cytomegalovirus ( ... Difficulty swallowing and painful swallowing Fever and chills Yeast infection of the tongue and lining of the ...

  13. Esophageal Cancer

    MedlinePlus

    ... Resources Conducting Clinical Trials Statistical Tools and Data Terminology Resources NCI Data Catalog Cryo-EM NCI's Role ... release mucus and other fluids. Smoking and heavy alcohol use increase the risk of esophageal squamous cell ...

  14. Esophageal perforation

    MedlinePlus

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

  15. Esophagitis in Adolescents.

    PubMed

    Putnam, Philip E

    2016-01-01

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

  16. A case of cervical esophageal duplication cyst in a newborn infant.

    PubMed

    Kawashima, Shoko; Segawa, Osamu; Kimura, Shuri; Tsuchiya, Masayoshi; Henmi, Nobuhide; Hasegawa, Hisaya; Fujibayashi, Mariko; Naritaka, Yoshihiko

    2016-12-01

    Esophageal duplication cyst is a rare congenital anomaly resulting from a foregut budding error during the fourth to sixth week of embryonic development. Cervical esophageal duplication cysts are very rare and may cause respiratory distress in infancy. A full-term newborn girl who was born by normal delivery was transferred to our hospital because of swelling of the right anterior neck since birth. Cervical ultrasonography showed a 40 × 24 × 33 mm simple cyst on the right neck. Tracheal intubation was required at 2 weeks of age because of worsening external compression of the trachea. Fine-needle aspiration cytology revealed the existence of ciliated epithelium. At 1 month of age, exploration was performed through a transverse neck incision. The cyst had a layer of muscle connected to the lateral wall of the esophagus. Histopathological diagnosis was a cervical esophageal duplication cyst. We describe the clinical features of infantile cervical esophageal duplication cysts based on our experience of this rare disease in a neonate, along with a review of 19 cases previously reported in literature. PMID:27037803

  17. Human esophageal myofibroblasts secrete proinflammatory cytokines in response to acid and Toll-like receptor 4 ligands.

    PubMed

    Gargus, Matthew; Niu, Chao; Vallone, John G; Binkley, Jana; Rubin, Deborah C; Shaker, Anisa

    2015-06-01

    The pathophysiology of esophageal injury, repair, and inflammation in gastroesophageal reflux-disease (GERD) is complex. Whereas most studies have focused on the epithelial response to GERD injury, we are interested in the stromal response. We hypothesized that subepithelial esophageal myofibroblasts in GERD secrete proinflammatory cytokines in response to injurious agents encountered via epithelial barrier breaches or through dilated epithelial intercellular spaces. We determined the percentage of myofibroblasts [-smooth muscle actin (-SMA)+vimentin+CD31-] in the subepithelial GERD and normal esophageal stroma by immunomorphologic analysis. We performed -SMA coimmunostaining with IL-6 and p65. We established and characterized primary cultures of -SMA+vimentin+CD31-CD45- human esophageal myofibroblasts (HuEso MFs). We modeled GERD by treatment with pH 4.5-acidified media and Toll-like receptor 4 (TLR4) ligands, LPS and high-mobility group box 1 protein (HMGB1), and determined myofibroblast cytokine secretion in response to GERD injury. We demonstrate that spindle-shaped cell myofibroblasts are located near the basement membrane of stratified squamous epithelium in normal esophagus. We identify an increase in subepithelial myofibroblasts and activation of proinflammatory pathways in patients with GERD. Primary cultures of stromal cells obtained from normal esophagus retain myofibroblast morphology and express the acid receptor transient receptor potential channel vanilloid subfamily 1 (TRPV1) and TLR4. HuEso MFs stimulated with acid and TLR4 agonists LPS and HMGB1 increase IL-6 and IL-8 secretion via TRPV1 and NF-B activation. Our work implicates a role for human subepithelial stromal cells in the pathogenesis of GERD-related esophageal injury. Findings of this study can be extended to the investigation of epithelial-stromal interactions in inflammatory esophageal mucosal disorders. PMID:25882613

  18. Human esophageal myofibroblasts secrete proinflammatory cytokines in response to acid and Toll-like receptor 4 ligands

    PubMed Central

    Gargus, Matthew; Niu, Chao; Vallone, John G.; Binkley, Jana; Rubin, Deborah C.

    2015-01-01

    The pathophysiology of esophageal injury, repair, and inflammation in gastroesophageal reflux-disease (GERD) is complex. Whereas most studies have focused on the epithelial response to GERD injury, we are interested in the stromal response. We hypothesized that subepithelial esophageal myofibroblasts in GERD secrete proinflammatory cytokines in response to injurious agents encountered via epithelial barrier breaches or through dilated epithelial intercellular spaces. We determined the percentage of myofibroblasts [α-smooth muscle actin (α-SMA)+vimentin+CD31−] in the subepithelial GERD and normal esophageal stroma by immunomorphologic analysis. We performed α-SMA coimmunostaining with IL-6 and p65. We established and characterized primary cultures of α-SMA+vimentin+CD31−CD45− human esophageal myofibroblasts (HuEso MFs). We modeled GERD by treatment with pH 4.5-acidified media and Toll-like receptor 4 (TLR4) ligands, LPS and high-mobility group box 1 protein (HMGB1), and determined myofibroblast cytokine secretion in response to GERD injury. We demonstrate that spindle-shaped cell myofibroblasts are located near the basement membrane of stratified squamous epithelium in normal esophagus. We identify an increase in subepithelial myofibroblasts and activation of proinflammatory pathways in patients with GERD. Primary cultures of stromal cells obtained from normal esophagus retain myofibroblast morphology and express the acid receptor transient receptor potential channel vanilloid subfamily 1 (TRPV1) and TLR4. HuEso MFs stimulated with acid and TLR4 agonists LPS and HMGB1 increase IL-6 and IL-8 secretion via TRPV1 and NF-κB activation. Our work implicates a role for human subepithelial stromal cells in the pathogenesis of GERD-related esophageal injury. Findings of this study can be extended to the investigation of epithelial-stromal interactions in inflammatory esophageal mucosal disorders. PMID:25882613

  19. Eosinophilic esophagitis

    PubMed Central

    Gupte, Anand R; Draganov, Peter V

    2009-01-01

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

  20. Pediatric esophageal scintigraphy. Results of 200 studies

    SciTech Connect

    Guillet, J.; Wynchank, S.; Basse-Cathalinat, B.; Christophe, E.; Ducassou, D.; Blanquet, P.

    1983-09-01

    Esophageal transit of a small volume of watery liquid has been observed scintigraphically in 200 studies performed on patients aged between 6 days and 16 years. Qualitative information concerning esophageal morphology and function in the various phases of deglutition, and scintigraphic features of achalasia, stenosis, and other pathologies are described. Measured esophageal transit time and its normal variation, its relevance to the diagnosis of esophagitis, and the monitoring of treatment are discussed. This technique observing distinct deglutitions has proven a useful diagnostic tool. Its advantages and limitations are discussed in comparison with other methods.

  1. Eosinophilic Esophagitis

    PubMed Central

    Furuta, Glenn T.; Katzka, David A.

    2016-01-01

    Once considered a rare condition, eosinophilic esophagitis is now one of the most common conditions diagnosed during the assessment of feeding problems in children and during the evaluation of dysphagia and food impaction in adults.1 The entity exists worldwide but has been most extensively studied in Western countries, where its prevalence has been estimated to be 0.4% among all children and adults.2 Whether eosinophilic esophagitis is truly a new disease or simply a recently recognized one is uncertain.3 In this review, we consider the diagnostic criteria, pathophysiological and clinical features, and treatment of this increasingly prevalent disease. PMID:26488694

  2. 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

  3. Whole genome expression array profiling highlights differences in mucosal defense genes in Barrett's esophagus and esophageal adenocarcinoma.

    PubMed

    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

  4. 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

  5. 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

  6. 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

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

    PubMed

    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

    2015-10-01

    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

  8. 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

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

    PubMed Central

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

    2015-01-01

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

  10. Esophageal perforation

    MedlinePlus

    ... esophagus into the space around the lungs Collapsed lung. X-rays taken after you drink a non-harmful dye can help pinpoint the location of the perforation. You may also have chest CT scan look for an abscess in the chest or esophageal cancer.

  11. [Eosinophilic esophagitis].

    PubMed

    Couto, Mariana; Rodrigues, Susana; Piedade, Susana; Gaspar, Ângela; Morais-Almeida, Mário; Macedo, Guilherme

    2011-12-01

    Eosinophilic esophagitis (EE) is an inflammatory disease of the esophagus characterized by significant and isolated infiltration of the esophageal mucosa by eosinophils, associated with clinical symptoms of esophageal dysfunction, affecting children and adults. It is an increasingly frequent cause of symptoms similar to gastroesophageal reflux disease but refractory to anti-acid therapeutic. It is commonly associated with food allergies or other atopic diseases. Since there are no symptoms, signs, serological biomarkers or endoscopic findings pathognomonic of EE, the diagnosis requires a high degree of suspicion; moreover, due to its chronic relapsing nature the potential to cause major esophageal structural changes, its early recognition and close cooperation between gastroenterologists and immunoallergologists is essential for the timely institution of appropriate therapy. The treatment is based on two main strategies: diet and / or pharmacotherapy, depending on the co-existence of sensitization to food allergens. It is our aim to review this issue, considering recent guidelines, as well as propose a diagnostic and therapeutic algorithm. PMID:22863504

  12. 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

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

    PubMed Central

    2013-01-01

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

  14. 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

  15. 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

  16. 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

  17. Radiation esophagitis.

    PubMed

    Murro, Diana; Jakate, Shriram

    2015-06-01

    The esophagus is frequently exposed to radiation during treatment of advanced stages of common cancers such as lung, breast, and esophagus. However, symptomatic radiation esophagitis requiring endoscopic and histologic evaluation occurs quite rarely, affecting less than 1% of patients receiving radiation treatment. Symptoms occur acutely, generally within the first 2 months. Patients typically present with nonspecific symptoms such as dysphagia and odynophagia. Endoscopic changes such as erythema and ulceration are also nonspecific and nondiagnostic. Biopsies from affected areas show variable inflammatory changes and radiation-related atypia of endothelial and stromal cells. Such atypia mimics cytomegalovirus cytopathic changes, which are ruled out through absence of immunostaining. Radiation esophagitis is thus clinically unsuspected and endoscopically and histologically quite different from the more common and familiar radiation proctitis for which angioectasia is the predominant finding. PMID:26030254

  18. Eosinophilic esophagitis–linked calpain 14 is an IL-13–induced protease that mediates esophageal epithelial barrier impairment

    PubMed Central

    Davis, Benjamin P.; Stucke, Emily M.; Khorki, M. Eyad; Litosh, Vladislav A.; Rymer, Jeffrey K.; Rochman, Mark; Travers, Jared; Kottyan, Leah C.; Rothenberg, Marc E.

    2016-01-01

    We recently identified a genome-wide genetic association of eosinophilic esophagitis (EoE) at 2p23 spanning the calpain 14 (CAPN14) gene, yet the causal mechanism has not been elucidated. We now show that recombinant CAPN14 cleaves a calpain-specific substrate and is inhibited by 4 classical calpain inhibitors: MDL-28170, acetyl-calpastatin, E-64, and PD151746. CAPN14 is specifically induced (>100-fold) in esophageal epithelium after IL-13 treatment. Epithelial cells overexpressing CAPN14 display impaired epithelial architecture, characterized by acantholysis, epidermal clefting, and epidermolysis. CAPN14 overexpression impairs epithelial barrier function, as demonstrated by decreased transepithelial resistance (2.1-fold) and increased FITC-dextran flux (2.6-fold). Epithelium with gene-silenced CAPN14 demonstrates increased dilated intercellular spaces (5.5-fold) and less organized basal cell layering (1.5-fold) following IL-13 treatment. Finally, CAPN14 overexpression results in loss of desmoglein 1 (DSG1) expression, whereas the IL-13–induced loss of DSG1 is normalized by CAPN14 gene silencing. Importantly, these findings were specific to CAPN14, as they were not observed with modulation of CAPN1 expression. These results, along with the potent induction of CAPN14 by IL-13 and genetic linkage of EoE to the CAPN14 gene locus, demonstrate a molecular and cellular pathway that contributes to T helper type 2 responses in mucosal epithelium. PMID:27158675

  19. 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

  20. Nanoscale markers of esophageal field carcinogenesis: potential implications for esophageal cancer screening

    PubMed Central

    Konda, Vani JA; Cherkezyan, Lusik; Subramanian, Hariharan; Wroblewski, Kirsten; Damania, Dhwanil; Becker, Valentin; Gonzalez, Mariano Haba Ruiz; Koons, Ann; Goldberg, Michael; Ferguson, Mark K; Waxman, Irving; Roy, Hermant K; Backman, Vadim

    2014-01-01

    Background and study aims Esophageal adenocarcinoma (EAC) has a dismal prognosis unless treated early or prevented at the precursor stage of Barrett’s esophagus-associated dysplasia. However, some patients with cancer or dysplastic Barrett’s esophagus (DBE) may not be captured by current screening and surveillance programs. Additional screening techniques are needed to determine who would benefit from endoscopic screening or surveillance. Partial wave spectroscopy (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld), a statistic that characterizes the spatial distribution of the intracellular mass at the nanoscale level and thus provides insights into the cell nanoscale architecture beyond that which is revealed by conventional microscopy. The aim of the present study was to compare the disorder strength measured by PWS in normal squamous epithelium in the proximal esophagus to determine whether nanoscale architectural differences are detectable in the field area of EAC and Barrett’s esophagus. Methods During endoscopy, proximal esophageal squamous cells were obtained by brushings and were fixed in alcohol and stained with standard hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells was determined by PWS. Results A total of 75 patient samples were analyzed, 15 of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non-dysplastic Barrett’s esophagus; 32 of the patients, most of whom had reflux symptoms, acted as controls. The mean disorder strength per patient in cytologically normal squamous cells in the proximal esophagus of patients with EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also had a disorder strength 1.63-times higher than controls (P<0.01). Conclusion Intracellular nanoarchitectural changes were found in the proximal squamous epithelium in patients harboring distal EAC and DBE using PWS. Advances in this technology and the biological

  1. Esophageal pH monitoring

    MedlinePlus

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

  2. 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

  3. Role of ion transporters in the bile acid-induced esophageal injury.

    PubMed

    Laczkó, Dorottya; Rosztóczy, András; Birkás, Klaudia; Katona, Máté; Rakonczay, Zoltán; Tiszlavicz, László; Róka, Richárd; Wittmann, Tibor; Hegyi, Péter; Venglovecz, Viktória

    2016-07-01

    Barrett's esophagus (BE) is considered to be the most severe complication of gastro-esophageal reflux disease (GERD), in which the prolonged, repetitive episodes of combined acidic and biliary reflux result in the replacement of the squamous esophageal lining by columnar epithelium. Therefore, the acid-extruding mechanisms of esophageal epithelial cells (EECs) may play an important role in the defense. Our aim was to identify the presence of acid/base transporters on EECs and to investigate the effect of bile acids on their expressions and functions. Human EEC lines (CP-A and CP-D) were acutely exposed to bile acid cocktail (BAC) and the changes in intracellular pH (pHi) and Ca(2+) concentration ([Ca(2+)]i) were measured by microfluorometry. mRNA and protein expression of ion transporters was investigated by RT-PCR, Western blot, and immunohistochemistry. We have identified the presence of a Na(+)/H(+) exchanger (NHE), Na(+)/HCO3 (-) cotransporter (NBC), and a Cl(-)-dependent HCO3 (-) secretory mechanism in CP-A and CP-D cells. Acute administration of BAC stimulated HCO3 (-) secretion in both cell lines and the NHE activity in CP-D cells by an inositol triphosphate-dependent calcium release. Chronic administration of BAC to EECs increased the expression of ion transporters compared with nontreated cells. A similar expression pattern was observed in biopsy samples from BE compared with normal epithelium. We have shown that acute administration of bile acids differently alters ion transport mechanisms of EECs, whereas chronic exposure to bile acids increases the expression of acid/base transporters. We speculate that these adaptive processes of EECs represent an important mucosal defense against the bile acid-induced epithelial injury. PMID:27198194

  4. 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.

  5. Human lung cancer cell lines express cell membrane complement inhibitory proteins and are extremely resistant to complement-mediated lysis; a comparison with normal human respiratory epithelium in vitro, and an insight into mechanism(s) of resistance.

    PubMed

    Varsano, S; Rashkovsky, L; Shapiro, H; Ophir, D; Mark-Bentankur, T

    1998-08-01

    Human lung cancer expresses cell membrane complement inhibitory proteins (CIP). We investigated whether human lung cancer cell lines also express cell-membrane CIP molecules and whether the biology of CIP molecules in these cell lines differs from that of CIP in normal human respiratory epithelium in culture. The cell lines ChaGo K-1 and NCI-H596 were compared with normal human nasal epithelium in primary cultures in respect to the level of cell membrane CIP expression of membrane cofactor protein (MCP; CD46), decay-accelerating factor (DAF; CD55) and CD59, in respect to the level of cell resistance to complement-mediated lysis, and in respect to the contribution of cell membrane CIP to cell resistance against complement-mediated lysis. We found, using flow cytometry, that both human lung cancer cell lines expressed MCP, DAF and CD59, as did normal nasal epithelial cells. However, normal cells showed a large subpopulation of low DAF-expressing cells (60% of all cells) and a smaller subpopulation of high DAF-expressing cells (40%), while the lung cancer cell lines showed only one cell population, of high DAF expression. In addition, both lung cancer cell lines expressed higher MCP levels, and NCI-H596 cells showed higher levels of CD59. Cell resistance to complement-mediated lysis of both lung cancer cell lines was much higher than that of normal cells. Fifty percent normal human serum, under the same concentrations of complement activators, induced lysis of less than a mean of 10% of lung cancer cells, while lysing up to a mean of 50% of nasal epithelial cells. Lung cancer cell resistance to complement was due to its ability to prevent significant activation of complement upon its cell membrane, as manifested by a failure of complement activators to increase cell membrane deposition of C3-related fragments. The exact mechanism for this resistance remains obscure. Unexpectedly, neutralizing antibodies, anti-MCP and anti-DAF were entirely ineffective and anti-CD59

  6. Management of delayed intrathoracic esophageal perforation with modified intraluminal esophageal stent.

    PubMed

    Zhou, J-H; Gong, T-Q; Jiang, Y-G; Wang, R-W; Zhao, Y-P; Tan, Q-Y; Ma, Z; Lin, Y-D; Deng, B

    2009-01-01

    In this article, we reviewed our experience of treatment of the delayed intrathoracic nonmalignant esophageal perforation employing modified intraluminal esophageal stent. Between February 1990 and August 2006, eight patients were included in this study. Five patients experienced sepsis. The interval time between perforation and stent placement ranged from 36 h to 27 days (average, 8.6 days). Esophageal stenting and throracotomy for foreign body removal were performed in four patients. The remaining four patients underwent stent placement and thoracostomy. Nutrition was initiated through gastrostomy after 7 to 10 days after the stenting. The stent was removed after the patients resumed oral intake of food and the esophagogram showed that perforation was closed. There was no death in this group. Signs of sepsis remitted 1 week after stent placement. Complications included stress ulcer, stimulative cough, and pneumonia each. Stent removal ranged 32 to 120 days (average 66.7) after its placement. The stent was kept in place for 4 months to prevent formation of esophageal stricture in one patient with caustic esophageal burns. The follow-up was completed in all the patients. The mean follow-up period was 59 months (range 12-180). One patient with caustic esophageal burn underwent cicatricial esophagectomy and gastric transposition 3 years later due to the esophageal stricture. Barium swallow demonstrated that there was a diverticulum-like outpouching in one patient and slight esophageal stricture at T2 and T3 level in another. One patient developed reflux esophagitis 5 years after stent removal. All the patients finally had a normal intake of food. Modified esophageal stenting is an effective method to manage the delayed intrathoracic esophageal perforation. Prevention of stent migration and its convenient adjustment might be the major advantages of this method. PMID:19191858

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

    PubMed Central

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

    2014-01-01

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

  8. Knockdown of DDX46 inhibits proliferation and induces apoptosis in esophageal squamous cell carcinoma cells.

    PubMed

    Li, Bin; Li, Yu-Min; He, Wen-Ting; Chen, Hao; Zhu, Hong-Wen; Liu, Tao; Zhang, Jian-Hua; Song, Tie-Niu; Zhou, Ya-Li

    2016-07-01

    Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma and remains the leading cause of cancer-related death worldwide. DEAD-box RNA helicases play critical roles in cellular metabolism and in many cases have been implicated in cellular proliferation and neoplastic transformation. DDX46 belongs to DEAD-box helicase family, the expression pattern of DDX46 in ESCC tissues and the biologic role in ESCC progression have not been implicated previously. In this study, DDX46 expression in human ESCC and adjacent normal tissues were explored using immunohistochemistry, and ESCC cell lines compared with normal esophageal epithelium cell were quantified using real‑time PCR. Next, lentivirus-mediated RNA interference was applied to silence DDX46 in TE-1 and Eca-109 cells. Cell growth was monitored using high content screening. Cell viability was measured by MTT assay. Cell colony-forming capacity was measured by colony formation assay. Cell cycle progression and apoptosis were determined by flow cytometry. Further, the stress and apoptosis signaling antibody array kit was used to detect the changes of signaling molecules in TE-1 cells after DDX46 knockdown. We found that DDX46 was significantly upregulated in ESCC tissues and cells compared with normal tissues and cells. DDX46 knockdown led to decreased proliferation and increased apoptosis in TE-1 and Eca-109 cells. Moreover, DDX46 silencing resulted in apoptotic induction via decreased phosphorylation of Akt and IκBα, as well as negative regulation of NF-κB signaling. In conclusion, these results demonstrate that DDX46 knockdown inhibited cell growth, and induced apoptosis, suggest that DDX46 is critical for ESCC cells proliferation. In addition, this study provides a foundation for further study into the clinical potential diagnosis and novel therapeutic target for ESCC. PMID:27176873

  9. 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

  10. 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

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

    PubMed

    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

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

    PubMed

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

    2016-08-01

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

  13. 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.

  14. Perception of Syllable Stress in Esophageal Speech.

    ERIC Educational Resources Information Center

    Walker, Christopher Niles; Morris, Hughlett L.

    1988-01-01

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

  15. Caustic ingestion: a possible cause of eosinophilic esophagitis?

    PubMed

    Homan, Matjaž; Orel, Rok; Liacouras, Chris

    2013-04-01

    Eosinophilic esophagitis (EoE) is an emerging disease in both pediatric and adult patients. It is a chronic disease of the esophagus and refers to intense eosinophilic infiltration limited to the esophageal epithelium in the absence of gastroesophageal reflux disease. In most patients, EoE is thought to be part of an allergic response to food antigens or aeroallergens. One such trigger could be caustic damage of the mucosa. To the best of our knowledge, the following case report describes for the first time the possible association between caustic injury of the esophagus and EoE. PMID:23478872

  16. ESOPHAGEAL DYSMOTILITY IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS. A STUDY USING PROLONGED ESOPHAGEAL MANOMETRY

    PubMed Central

    Nurko, Samuel; Rosen, Rachel; Furuta, Glenn T.

    2010-01-01

    Background The pathophysiology of dysphagia in patients with eosinophilic esophagitis (EoE) is unknown, but may be related to abnormal esophageal motor function. Symptoms rarely occur during stationary esophageal manometry so it has been difficult to establish an association between symptoms and motor events. Aim To evaluate esophageal motor function in children with EoE with the use of stationary manometry and ambulatory prolonged esophageal manometry and pH-metry (PEMP) Methods PEMP was performed in children with EoE, compared with controls and children with GERD. Effective peristalsis was considered when the esophageal contractions had a normal amplitude and propagation. Results expressed as mean ± S.E. Results Seventeen patients with EoE, 13 with GERD and 11 controls were studied. Values are expressed as mean ± se. Stationary manometry identified abnormal peristalsis in 41% of children with EoE. During PEMP, children with EoE had an increased number of isolated (16.7 ± 3.8 vs 9.5 ± 1.6 vs 6.5 ± 1.1 ; p< 0.03) and high amplitude contractions (4.1 ± 1.2 vs 1.8 ±0.8 vs 0.1 ± 0.1; p< 0.03), and more % ineffective peristalsis both during fasting (70.5% ± 2.5 vs 57.8% ± 3.0 vs 53.8% ± 1.9; p <0.05) and during meals (68.4 ± 3.4 vs 55.3 ± 2.8 vs 48.1 ± 2.8; p < 0.05) when compared with children with GERD and controls. Thirteen patients with EoE experienced 21 episodes of dysphagia and all correlated with simultaneous abnormal motor function. Conclusions PEMP allowed the detection of ineffective peristalsis in children with EoE. Symptoms observed in children with EoE may be related to esophageal motor dysfunction. PMID:19755968

  17. [Morphological changes in esophageal mucosa in children with overweight].

    PubMed

    Dubrovskaia, M I; Tertychnyĭ, A S; Mukhina, Iu G; Volodina, I I; Mamchenko, S I

    2010-01-01

    In present work we studied the morphological features of the esophageal mucosa in 63 children with endoscopic diagnosis of the distal esophagitis having overweight and normal weight of a body. The biopsies were taken at level of 3 cm above a Z-line and at level of 1 cm above a Z-line. Dystrophic and dysregenerative changes were revealed at the majority of children and half of children had inflammatory changes of the esophageal mucosa regardless of weight of a body. These changes are more pronounced at level of 1 cm above a Z-line, their occurrence decreases with a distance from low esophageal sphincter. We used the pathology score system for assess the esophageal biopsies. According our scale we obtained following results: at level of 1 cm above Z-lines at 95% of children had the normal, minimum or mild features of esophagitis regardless of weight of a body. Morphological evidence of a reflux esophagitis was diagnosed statistically more often at level of 1 cm above Z lines in comparison with level of 3 cm above Z-lines (p < 0.01) as among children with overweight of the body (78 and 43% accordingly), and among children with normal weight of the body (78 and 35% accordingly). The obtained data will be allowed to avoid hyperdiagnostics of esophageal lesions in children. PMID:20405708

  18. Esophageal culture

    MedlinePlus

    ... lab. There, it is placed in a special dish (culture) and watched for the growth of bacteria, ... means that no germs grew in the laboratory dish. Normal value ranges may vary slightly among different ...

  19. 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 Barrett’s esophagus; micronutrients, trace elements, and risk of Barrett’s 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

  20. 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

  1. Functional luminal imaging probe topography: an improved method for characterizing esophageal distensibility in eosinophilic esophagitis

    PubMed Central

    Kahrilas, Peter J.; Xiao, Yinglian; Nicodème, Frédéric; Gonsalves, Nirmala; Hirano, Ikuo; Pandolfino, John E.

    2013-01-01

    Objectives: The aims of this study were to develop a new method for analysis and presentation of esophageal distensibility data using high-resolution impedance planimetry recordings during a volume-controlled distention. Methods: Two control subjects and six patients with eosinophilic esophagitis (EoE) with stricture, narrow caliber or normal endoscopy according to EndoFLIP studies were included for analysis. Median filtering and pulse detection techniques were applied to the pressure signal and a wavelet decomposition technique was applied to the 16 channels of raw esophageal diameter data to reduce vascular artifact, respiratory effect and remove esophageal contraction interference. These data were used to generate a functional luminal imaging probe (FLIP) topography plot that describes regional variation of cross-sectional area (CSA). A previously developed computer program was used to calculate and model the CSA-pressure data to derive the slope of line fitting and distension plateau for each individual subject. The results were compared among the four endoscopic phenotypes. Results: Patients with EoE and normal endoscopy had similar esophageal distensibility parameters to those of normal controls whereas patients with EoE and stricture or narrow caliber had much lower distensibility than patients with EoE and normal endoscopy. The FLIP topography plots provided a global assessment of the esophageal distensibility along the axial plane of measurement that differentiated patients with varying degrees of endoscopic abnormality. Conclusions: New techniques can be leveraged to improve data analysis and presentation using EndoFLIP assessment of the esophageal body in EoE. These techniques may be helpful in defining clinically relevant phenotypes and guiding treatment strategies and should be helpful in structuring future outcome trials. PMID:23503784

  2. Intra-abdominal esophageal duplication cyst in an adult.

    PubMed

    Kim, Young Wan; Sohn, Tai Il; Shim, Hyo Sup; Kim, Choong Bai

    2005-12-31

    Esophageal duplication cysts are congenital anomalies of the foregut that are rarely found in the abdomen. An accurate preoperative diagnosis is not always possible, so the definitive diagnosis can be made by histologic examination of the surgical specimen. We experienced a case of Intra-abdominal esophageal duplication cyst in a 52-year-old female, who initially presented with an esophageal submucosal tumor on upper gastrointestinal endoscopy. She did not have any gastrointestinal symptoms. Barium esophagography, chest computed tomography scan and endoscopic ultrasonography demonstrated the cystic lesion in the intra-abdominal esophagus. Transhiatal enucleation of the lesion was performed successfully via the abdominal approach with no postoperative complications. Histologic study showed that the cyst wall contained a two-layered muscle coat and the surface of the lumen was lined by pseudo-ciliated columnar epithelium. The patient has been doing well without any complaints for 3 months of follow-up period. PMID:16385665

  3. 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.

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

    PubMed Central

    Doucet-O'Hare, Tara T.; Rodić, 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

    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

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

    PubMed

    Doucet-O'Hare, Tara T; Rodić, 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

  6. Functional esophageal disorders

    PubMed Central

    Clouse, R; Richter, J; Heading, R; Janssens, J; Wilson, J

    1999-01-01

    The functional esophageal disorders include globus, rumination syndrome, and symptoms that typify esophageal diseases (chest pain, heartburn, and dysphagia). Factors responsible for symptom production are poorly understood. The criteria for diagnosis rest not only on compatible symptoms but also on exclusion of structural and metabolic disorders that might mimic the functional disorders. Additionally, a functional diagnosis is precluded by the presence of a pathology-based motor disorder or pathological reflux, defined by evidence of reflux esophagitis or abnormal acid exposure time during ambulatory esophageal pH monitoring. Management is largely empirical, although efficacy of psychopharmacological agents and psychological or behavioral approaches has been established for serveral of the functional esophageal disorders. As gastroesophageal reflux disease overlaps in presentation with most of these disorders and because symptoms are at least partially provoked by acid reflux events in many patients, antireflux therapy also plays an important role both in diagnosis and management. Further understanding of the fundamental mechanisms responsible for symptoms is a priority for future research efforts, as is the consideration of treatment outcome in a broader sense than reduction in esophageal symptoms alone. Likewise, the value of inclusive rather than restrictive diagnostic criteria that encompass other gastrointestinal and non-gastrointestinal symptoms should be examined to improve the accuracy of symptom-based criteria and reduce the dependence on objective testing.


Keywords: globus; rumination; chest pain; esophageal motility disorders; esophageal spasm; gastroesophageal reflux disease; Rome II PMID:10457042

  7. Eosinophilic esophagitis: an autoimmune esophageal disorder.

    PubMed

    Malhotra, Neha; Levine, Jeremiah

    2014-12-01

    Eosinophilic esophagitis (EoE) represents a chronic, immune/antigen-mediated esophageal inflammatory disease associated with esophageal dysfunction resulting from severe inflammation. The incidence and prevalence of EoE have been increasing in the past decade; however, the reason for this increase is unclear. There is a chronic inflammatory infiltrate that is present in EoE which promotes inflammation, symptoms, and dysfunction. In addition to eosinophils, interleukin (IL)-5 expressing T cells, B cells, eotaxin-3, IL-13, and IgE-bearing mast cells are present in EoE and are thought to contribute to the disease process. Eosinophils are pro-inflammatory and modulate multiple aspects of the immune response. Eosinophils produce a wide range of inflammatory cytokines, chemokines, granulocyte-monocyte colony-stimulating factors, and tumor necrosis factors. Once activated, eosinophils release granule components, which are toxic to a variety of tissues. Transforming growth factor β1 is a pro-fibrotic molecule produced by epithelial and inflammatory cells, is overexpressed in EoE, and plays a role in esophageal remodeling. Fibrous remodeling in EoE could be associated with symptoms of dysphagia and may explain and predict future esophageal strictures and dysmotility. EoE is a complex disease involving multiple activation pathways, a large number of cells, and various inflammatory molecules. It, along with other atopic disease, is becoming increasingly prevalent and has an important genetic load and may represent as an immunological tolerance disorder of the GI tract. PMID:25499460

  8. High prevalence of esophageal dysmotility in asymptomatic obese patients

    PubMed Central

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

    2014-01-01

    % [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

  9. Intraluminal acid activates esophageal nodose C fibers after mast cell activation.

    PubMed

    Zhang, Shizhong; Liu, Zhenyu; Heldsinger, Andrea; Owyang, Chung; Yu, Shaoyong

    2014-02-01

    Acid reflux in the esophagus can induce esophageal painful sensations such as heartburn and noncardiac chest pain. The mechanisms underlying acid-induced esophageal nociception are not clearly understood. In our previous studies, we characterized esophageal vagal nociceptive afferents and defined their responses to noxious mechanical and chemical stimulation. In the present study, we aim to determine their responses to intraluminal acid infusion. Extracellular single-unit recordings were performed in nodose ganglion neurons with intact nerve endings in the esophagus using ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal intraluminal acid perfusion were compared in naive and ovalbumin (OVA)-challenged animals, followed by measurements of transepithelial electrical resistance (TEER) and the expression of tight junction proteins (zona occludens-1 and occludin). In naive guinea pigs, intraluminal infusion with either acid (pH = 2-3) or capsaicin did not evoke an action potential discharge in esophageal nodose C fibers. In OVA-sensitized animals, following esophageal mast cell activation by in vivo OVA inhalation, intraluminal acid infusion for about 20 min started to evoke action potential discharges. This effect is further confirmed by selective mast cell activation using in vitro tissue OVA challenge in esophageal-vagal preparations. OVA inhalation leads to decreased TEER and zona occludens-1 expression, suggesting an impaired esophageal epithelial barrier function after mast cell activation. These data for the first time provide direct evidence of intraluminal acid-induced activation of esophageal nociceptive C fibers and suggest that mast cell activation may make esophageal epithelium more permeable to acid, which subsequently may increase esophageal vagal nociceptive C fiber activation. PMID:24264049

  10. Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line

    PubMed Central

    Niu, Chao; Chauhan, Uday; Gargus, Matthew; Shaker, Anisa

    2016-01-01

    Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies. PMID:27055018

  11. Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line.

    PubMed

    Niu, Chao; Chauhan, Uday; Gargus, Matthew; Shaker, Anisa

    2016-01-01

    Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies. PMID:27055018

  12. Candida Esophagitis in an Immunocompetent Pregnant Woman

    PubMed Central

    Kivnick, Seth

    1993-01-01

    Background: Nausea and vomiting are common during the first half of pregnancy and usually require only supportive measures. When symptoms are progressive and weight loss occurs, treatable causes should be sought by means of upper gastrointestinal endoscopy. We report a case of an immunocompetent gravida with invasive Candida albicans esophagitis. Case: The immunocompetent primigravida developed progressive nausea, vomiting, epigastric pain, and a 4.1 kg weight loss during the second trimester of pregnancy. Treatment with metoclopramide and cimetidine for presumed gastroesophageal reflux was not effective. The patient had normal T-cell CD4 and CD8 subsets and was human immunodeficiency virus (HIV) antibody negative. Upper gastrointestinal endoscopy revealed C. albicans esophagitis which was treated with oral nystatin. The esophagitis had resolved completely when reassessed postpartum. The use of histamine2 blockers is associated with an increased risk for fungal esophagitis and may have been a contributing cause in this case. Conclusion: Pregnant patients with persistent nausea, vomiting, and weight loss should be evaluated by endoscopy for fungal esophagitis. PMID:18475336

  13. 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 16.2±3.7μm, whereas that of IPCLs in cancerous lesions was 21.0±4.4μm. Conclusions The development of iodine-unstained areas tends to precede any changes in the vascularity of the esophageal surface epithelium. PMID:26301414

  14. Axial force measurement for esophageal function testing.

    PubMed

    Gravesen, Flemming H; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn Mohr

    2009-01-14

    The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the "golden standard" for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method. PMID:19132762

  15. Remodeling of the Fetal Collecting Duct Epithelium

    PubMed Central

    Hiatt, Michael J.; Ivanova, Larissa; Toran, Nuria; Tarantal, Alice F.; Matsell, Douglas G.

    2010-01-01

    Congenital urinary tract obstruction induces changes to the renal collecting duct epithelium, including alteration and depletion of intercalated cells. To study the effects of obstruction on the ontogeny of intercalated cell development, we examined normal and obstructed human fetal and postnatal kidneys. In the normal human fetal kidney, intercalated cells originated in the medullary collecting duct at 8 weeks gestation and remained most abundant in the inner medulla throughout gestation. In the cortex, intercalated cells were rare at 18 and 26 weeks gestation and observed at low abundance at 36 weeks gestation. Although early intercalated cells exhibit an immature phenotype, Type A intercalated cells predominated in the inner and outer medullae at 26 and 36 weeks gestation with other intercalated cell subtypes observed rarely. Postnatally, the collecting duct epithelium underwent a remodeling whereby intercalated cells become abundant in the cortex yet absent from the inner medulla. In 18-week obstructed kidneys with mild to moderate injury, the intercalated cells became more abundant and differentiated than the equivalent age-matched normal kidney. In contrast, more severely injured ducts of the late obstructed kidney exhibited a significant reduction in intercalated cells. These studies characterize the normal ontogeny of human intercalated cell development and suggest that obstruction induces premature remodeling and differentiation of the fetal collecting duct epithelium. PMID:20035053

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

    ClinicalTrials.gov

    2016-09-15

    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

  17. Comparison of long non-coding RNAs, microRNAs and messenger RNAs involved in initiation and progression of esophageal squamous cell carcinoma

    PubMed Central

    LI, SU-QING; LI, FENG; XIAO, YUN; WANG, CHUN-MEI; TUO, LEI; HU, JING; YANG, XIAO-BIN; WANG, JIN-SONG; SHI, WEI-HONG; LI, XIA; CAO, XIU-FENG

    2014-01-01

    Traditionally, cancer research has focused on protein-coding genes, which are considered the principal effectors and regulators of tumorigenesis. Non-coding RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have been widely reported to be important in the regulation of tumorigenesis and cancer development. However, to the best of our knowledge, investigation of the expression profiles of lncRNAs and a comparison of the involvement of lncRNAs, miRNAs and messenger RNAs (mRNAs) in esophageal tumorigenesis and development have not previously been performed. In the current study, intrinsic associations among the expression profiles of lncRNAs, miRNAs and mRNAs from normal esophageal tissues and those from cancer tissues were investigated. Oligonucleotide microarrays were used to detect the expression profiles of the three types of RNA in the canceration processes of human esophageal squamous cell carcinoma (ESCC) tissues. It was demonstrated that the different RNAs exhibit associated patterns of expression among normal esophageal epithelium, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and carcinoma tissues, particularly in the critical period of canceration (HGIN to ESCC). Furthermore, the results indicated a high level of similarity in the potential function of lncRNAs, miRNAs and mRNAs in the processes of ESCC development. In the current study, a first generation atlas of lncRNA profiling and its association with miRNAs and mRNAs in the canceration processes of ESCC were presented. PMID:24888564

  18. Endoscopic and Abdominal Management of Complete Benign Esophageal Obstruction

    PubMed Central

    2016-01-01

    Benign esophageal strictures leading to complete esophageal occlusion are well known. In the pre-endoscopic era, such cases required surgery, but over the last decade, various novel endoscopic techniques have been developed to prevent morbidity and mortality. A 37-year-old man presented after 1 year of dysphagia and weight loss, and was found to have complete esophageal obstruction, not allowing even passage of guidewire. We used a combination antegrade endoscopic abdominal procedures to deploy a stent, obviating the need for surgery. His symptoms improved dramatically, and the stent was successfully removed 12 weeks later. He is now swallowing normally and has gained significant weight. PMID:27144192

  19. Esophageal stricture - benign

    MedlinePlus

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

  20. [Esophageal motor disturbances in sclerodermia].

    PubMed

    Stanciu, C; Cijevschi, C; Dobrescu, A; Petrescu, Z

    1981-01-01

    By the manometric method the esophageal motility in 14 patients with sclerodermia was studied. All patients presented an esophageal motor dysfunction characterized by the decrease in amplitude of the spohageal contractions, presence of aperistaltic contractions, decrease of basal pressure of the lower esophageal sphincter and its incomplete relaxation at deglutition. These esophageal motor disturbances may appear in association or separately in the same patient. The pathogenesis of the esophageal motor dysfunction in sclerodermia is not yet fully understood. Besides the theoretical interest, the knowledge of the esophageal motor dysfunction in sclerodermia has also a practical value in respect of the tretment which is to be set up. PMID:25528800

  1. [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

  2. Altered Esophageal Histamine Receptor Expression in Eosinophilic Esophagitis (EoE): Implications on Disease Pathogenesis

    PubMed Central

    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

  3. Abnormalities of esophageal and gastric emptying in progressive systemic sclerosis

    SciTech Connect

    Maddern, G.J.; Horowitz, M.; Jamieson, G.G.; Chatterton, B.E.; Collins, P.J.; Roberts-Thomson, P.

    1984-10-01

    Gastric and esophageal emptying were assessed using scintigraphic techniques in 12 patients with progressive systemic sclerosis and 22 normal volunteers. Esophageal emptying was significantly delayed in the patient group, with 7 of the 12 patients beyond the normal range. Gastric emptying was slower in patients than in controls, with 9 patients being outside the normal range for solid emptying and 7 patients outside the normal range for liquid emptying. Findings from gastric and esophageal emptying tests generally correlated well with symptoms of dysphagia and gastroesophageal reflux. However, 2 patients with normal emptying studies had symptomatic heartburn, and 2 patients with delay of both solid and liquid gastric emptying gave no history of gastroesophageal reflux. Delayed gastric emptying may be an important factor in the development of upper gastrointestinal symptoms in patients with progressive systemic sclerosis.

  4. Esophageal pH monitoring

    MedlinePlus

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

  5. Achalasia and Esophageal Motility Disorders

    MedlinePlus

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

  6. General Information about Esophageal Cancer

    MedlinePlus

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

  7. 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 ...

  8. Clinical and endoscopic characteristics of drug-induced esophagitis

    PubMed Central

    Kim, Su Hwan; Jeong, Ji Bong; Kim, Ji Won; Koh, Seong-Joon; Kim, Byeong Gwan; Lee, Kook Lae; Chang, Mee Soo; Im, Jong Pil; Kang, Hyoun Woo; Shin, Cheol Min

    2014-01-01

    AIM: To investigate clinical, endoscopic and pathological characteristics of drug-induced esophagitis. METHODS: Data for patients diagnosed with drug-induced esophagitis from April 2002 to May 2013 was reviewed. Patients diagnosed with malignancy, viral or fungal esophagitis were excluded. Clinical, endoscopic and pathological characteristics of patients diagnosed with drug-induced esophagitis were analyzed. RESULTS: Seventy-eight patients were diagnosed with drug-induced esophagitis. Their mean age was 43.9 ± 18.9 years and 35.9% were male. Common symptoms were chest pain (71.8%), odynophagia (38.5%) and dysphagia (29.5%). The endoscopic location was in the middle third of esophagus in 78.2%. Endoscopic findings were ulcer (82.1%), erosion (17.9%), ulcer with bleeding (24.4%), coating with drug material (5.1%), impacted pill fragments (3.8%) and stricture (2.6%). Kissing ulcers were observed in 43.6%. The main causative agents were antibiotics and non-steroidal anti-inflammatory drugs. All the patients were treated with proton pump inhibitors (PPIs) or sucralfate, and the causative drugs were discontinued. Nineteen patients with drug-induced esophagitis were followed up with endoscopy and revealed normal findings, scars or healing ulcers. CONCLUSION: Drug-induced esophagitis mainly presents as chest pain, odynophagia and dysphagia, and may be successfully treated with PPIs and discontinuation of the causative drug. Kissing ulcers were observed in 43.6%. PMID:25152603

  9. 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-κB (NF-κB) dependent. Acid and/or bile salt incubations were performed in Het-1A cells. Experiments were performed with or without inhibiting the NF-κB 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-κB 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-κB pathway. PMID:24006894

  10. Minimally invasive surgery for esophageal achalasia

    PubMed Central

    Chen, Huan-Wen

    2016-01-01

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

  11. Small Cell Type of Esophageal Neuroendocrine Carcinoma Resembling a Submucosal Tumor.

    PubMed

    Chino, Osamu; Makuuchi, Hiroyasu; Ozawa, Soji; Shimada, Hideo; Nishi, Takayuki; Kise, Yoshifumi; Hara, Tadashi; Yamamoto, Soichiro; Kazuno, Akihito; Kajiwara, Hiroshi

    2015-07-01

    We report a rare case of primary small cell type esophageal neuroendocrine carcinoma with a unusual endoscopic form similar to a submucosal tumor with the results of the histological and immunohistochemical analyses. A 57-year-old woman with dysphagia was referred to our hospital for further examination and treatment, and was diagnosed as type 1s esophageal carcinoma in the middle thoracic esophagus. Endoscopy revealed a protruding esophageal carcinoma resembling a submucosal tumor with an irregular and nodular surface covered by non-neoplastic epithelium stained with iodine. Analysis of the esophageal biopsy specimen revealed poorly differentiated squamous cell carcinoma. Based on a diagnosis of type 1s carcinoma in the middle thoracic esophagus that was 5 cm in size longitudinally, a radical esophagectomy with three-field lymph node dissection was performed. The pathological examination with histological and immunohistochemical analysis of the resected specimen revealed a small cell type neuroendocrine carcinoma overlaid by a non-neoplastic epithelium, extending into the adventitia without lymph node metastasis (T3, N0, M0, Stage II). However, multiple metastases in the brain and lung developed 3 months postoperatively, and the patient died of the cancer 7 months after the operation. This was a rare case of a highly malignant primary small cell type esophageal neuroendocrine carcinoma showing extremely rare form. PMID:26150181

  12. Virological Diagnosis of Herpes Simplex Virus 1 Esophagitis by Quantitative Real-Time PCR Assay

    PubMed Central

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

    2012-01-01

    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 × 106 ± 1.1 × 108) than in histopathologically negative herpetic esophagitis (median = 3.1 × 103 ± 6.2 × 103) (P = 0.0009). Moreover, a receiver operating characteristics analysis revealed that a viral load threshold greater than 2.5 × 104 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. 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

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

    PubMed

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

    2015-03-14

    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

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

    PubMed

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

    1980-01-01

    Autoradiographic patterns of [3H]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. Whereas the normal tracheal basal layer exhibited an LI smaller than 1%, a clear difference between the carcinomas (in situ and invasive) on one hand (LI approximately 32%) and all the remaining epithelia on the other hand (LI approximately 18%) was detected. The LIs of the suprabasal cells exhibited a statistically significant difference between the squamous epithelia without atypia (LI approximately 2%) and the group comprising all the atypical lesions (LI approximately 9%). 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

  16. 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.

  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. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

    Knowles, M. R.; Stutts, M. J.; Spock, A.; Fischer, N.; Gatzy, J. T.; Boucher, R. C.

    1983-09-01

    The epithelium of nasal tissue excised from subjects with cystic fibrosis exhibited higher voltage and lower conductance than tissue from control subjects. Basal sodium ion absorption by cystic fibrosis and normal nasal epithelia equaled the short-circuit current and was amiloride-sensitive. Amiloride induced chloride ion secretion in normal but not cystic fibrosis tissue and consequently was more effective in inhibiting the short-circuit current in cystic fibrosis epithelia. Chloride ion-free solution induced a smaller hyperpolarization of cystic fibrosis tissue. The increased voltage and amiloride efficacy in cystic fibrosis reflect absorption of sodium ions across an epithelium that is relatively impermeable to chloride ions.

  19. 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 10 weeks. 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 6-10 weeks 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

  20. Methyl-methanesulfonate sensitivity 19 expression is associated with metastasis and chemoradiotherapy response in esophageal cancer

    PubMed Central

    Zhang, Jin-Liang; Wang, Hui-Yun; Yang, Qing; Lin, Shi-Yong; Luo, Guang-Yu; Zhang, Rong; Xu, Guo-Liang

    2015-01-01

    AIM: To investigate the clinical significance of methyl-methanesulfonate sensitivity 19 (MMS19) expression in esophageal squamous cell carcinoma (ESCC). METHODS: Between June 2008 and May 2013, specimens from 103 patients who underwent endoscopic biopsy for the diagnosis of ESCC at the endoscopy center of Sun Yat-Sen University Cancer Center were collected; 52 matched-normal esophageal squamous epithelium samples were biopsied as controls. MMS19 protein expression was measured by immunohistochemistry. Of the 103 cases of ESCC, 49 received radical surgery following neoadjuvant chemoradiotherapy consisting of concurrent radiation in a total dose of 40 Gy and two cycles of chemotherapy with vinorelbine and cisplatin. Relationships between MMS19 expression, clinicopathologic characteristics and chemoradiotherapy response were analyzed. RESULTS: The MMS19 protein could be detected in both the cytoplasm and nucleus of most specimens. High cytoplasmic expression of MMS19 was detected in 63.1% of ESCC samples, whereas high nuclear expression of MMS19 was found in 35.0%. High cytoplasmic MMS19 expression was associated with regional lymph node metastases (OR = 11.3, 95%CI: 2.3-54.7; P < 0.001) and distant metastases (OR = 13.1, 95%CI: 1.7-103.0; P = 0.002). Furthermore, high cytoplasmic MMS19 expression was associated with a response of ESCC to chemoradiotherapy (OR = 11.5, 95%CI: 3.0-44.5; P < 0.001), with a high cytoplasmic MMS19 expression rates in 79.3% and 25.0% of patients from the good chemoradiotherapy response group and poor response group, respectively. Nuclear MMS19 expression did not show any significant association with clinicopathologic characteristics or chemoradiotherapy response in ESCC. CONCLUSION: The results of our preliminary study suggest that MMS19 may be a potential new predictor of metastasis and chemoradiotherapy response in ESCC. PMID:25892874

  1. Effect of bolus composition on esophageal transit: concise communication

    SciTech Connect

    Fisher, R.S.; Malmud, L.S.; Applegate, G.; Rock, E.; Lorber, S.H.

    1982-10-01

    The technique of esophageal scintigraphy was developed as a sensitive, quantitative, noninvasive test of esophageal transit. Esophageal scintigraphy was performed in 40 asymptomatic normal volunteers in order to determine the effect on esophageal transit of the following: body posture (sitting vs. supine), liquid vs. solid, the solid being either a standard number4 gelatin capsule of the size used for antibiotic capsules, or a cube of solid food such as cooked chicken liver. The results showed that liquids emptied completely from the esophagus after one swallow, whether supine or sitting. Capsules or liver cubes, when ingested without water, frequently remained in the esophagus for up to two hours without the subject's having any sensation that the solid had not left the esophagus. Both capsules and liver cubes cleared the esophagus better in the upright than in the supine position. When gelatin capsules were swallowed with as little as 15 ml of water, but after a preliminary sip of water, there was complete transit in each case. The study suggests that the practice of assisting patients into a sitting position and instructing them to take a sip of water before attempting to swallow a capsule will assure better transit of the capsule even when swallowed with as little as 15 ml of water. This may reduce the incidence of esophagitis following oral antibiotics, and of esophageal erosions from aspirin-containing medications.

  2. Effect of bolus composition on esophageal transit: concise communication

    SciTech Connect

    Fisher, R.S.; Malmud, L.S.; Appelgate, G.; Rock, E.; Lorber, S.H.

    1982-10-01

    The technique of esophageal scintigraphy was developed as a sensitive, quantitative, noninvasive test of esophageal transit. Esophageal scintigraphy was performed in 40 asymptomatic normal volunteers in order to determine the effect on esophageal transit of the following: body posture (sitting vs. supine), liquid vs. solid, the solid being either a standard gelatin capsule of the size used for antibiotic capsules, or a cube of solid food such as cooked chicken liver. The results showed that liquids emptied completely from the esophagus after one swallow whether supine or sitting. Capsules or liver cubes, when ingested without water, frequently remained in the esophagus for up to two hours without the subject's having any sensation that the solid had not left the esophagus. Both capsules and liver cubes cleared the esophagus better in the upright than in the supine position. When gelatin capsules were swallowed with as little as 15 ml of water, but after a preliminary sip of water, there was complete transit in each case. The study suggests that the practice of assisting patients into a sitting position and instructing them to take a sip of water before attempting to swallow a capsule will assure better transit of the capsule even when swallowed with as little as 15 ml of water. This may reduce the incidence of esophagitis following oral antibiotics, and of esophageal erosions from aspirin-containing medications.

  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. Eosinophilic esophagitis in children with esophageal atresia.

    PubMed

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

    2014-01-01

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

  5. Aberrant esophageal HLA-DR expression in a high percentage of patients with Crohn's disease.

    PubMed

    Oberhuber, G; Püspök, A; Peck-Radosavlevic, M; Kutilek, M; Lamprecht, A; Chott, A; Vogelsang, H; Stolte, M

    1999-08-01

    Esophageal histology is not well studied in patients with Crohn's disease (CD). We, therefore, analyzed the histologic and immunohistologic appearance of esophageal mucosa in CD. Biopsy specimens taken from the esophagus of 57 consecutive patients with known CD of the large and/or small bowel, of 200 Crohn's-free controls, of 15 cases with ulcerative colitis, and of 5 cases with viral esophagitis were evaluated. In controls, most patients had either HLA-DR negative esophageal epithelium or showed focal or diffuse basal staining. HLA-DR expression of all epithelial layers (transepithelial staining) was observed in only four (2%) control subjects, in one case with herpes esophagitis, but not in patients with ulcerative colitis. In contrast, transepithelial HLA-DR expression was found in 19 (33%) patients with CD (p < 0.0001). In CD patients, it was associated with a significantly increased epithelial content in T-cells (CD3+, TIA-1+, granzyme B+), B-cells (CD79a+), natural killer cells (CD57+), and macrophages (CD68+). There was no correlation with either histological findings elsewhere in the upper gastrointestinal tract or with laboratory findings, symptoms, CDAI, or medication. Transepithelial esophageal HLA-DR expression is common in CD. Immunohistochemistry may prove useful in supporting the histologic diagnosis of CD in staging procedures, for initial diagnosis as well as in doubtful cases. PMID:10435568

  6. Esophageal contractions in type 3 achalasia esophagus: simultaneous or peristaltic?

    PubMed

    Kim, Tae Ho; Patel, Nirali; Ledgerwood-Lee, Melissa; Mittal, Ravinder K

    2016-05-01

    Absence of peristalsis and impaired relaxation of lower esophageal sphincter are the hallmarks of achalasia esophagus. Based on the pressurization patterns, achalasia has been subdivided into three subtypes. The goal of our study was to evaluate the esophageal contraction pattern and bolus clearance in type 3 achalasia esophagus. High-resolution manometry (HRM) recordings of all patients diagnosed with achalasia esophagus in our center between the years 2011 and 2013 were reviewed. Recordings of 36 patients with type 3 achalasia were analyzed for the characteristics of swallow-induced "simultaneous esophageal contraction." The HRM impedance recordings of 14 additional patients with type 3 achalasia were analyzed for bolus clearance from the impedance recording. Finally, the HRM impedance along with intraluminal ultrasound imaging was conducted in six patients to further characterize the simultaneous esophageal contractions. Among 187 achalasia patients, 30 were type 1, 121 type 2, and 36 type 3. A total of 434 swallows evaluated in type 3 achalasia patients revealed that 95% of the swallow-induced contractions met criteria for simultaneous esophageal contraction, based on the onset of contraction. Interestingly, the peak and termination of the majority of simultaneous esophageal contractions were sequential. The HRM impedance revealed that 94% of the "simultaneous contractions" were associated with complete bolus clearance. Ultrasound image analysis revealed that baseline muscle thickness of patients in type 3 achalasia is larger than normal but the pattern of axial shortening is similar to that in normal subjects. The majority of esophageal contractions in type 3 achalasia are not true simultaneous contractions because the peak and termination of contraction are sequential and they are associated with complete bolus clearance. PMID:26950858

  7. Olfactory Epithelium Grafts in the Cerebral Cortex: An Immunohistochemical Analysis

    PubMed Central

    Holbrook, Eric H.; DiNardo, Laurence J.; Costanzo, Richard M.

    2009-01-01

    Objective To develop an alternative model for studying the regenerative capacity of olfactory neurons. Study Design An immunohistochemical analysis of mouse olfactory epithelium transplanted to the cerebral cortex. Methods Strips of olfactory epithelium removed from donor mice at postnatal day 5 to day 20 were inserted into the parietal cortex of adult mice. Recipient animals were allowed to survive for 25 to 120 days and then perfused with 4% paraformaldehyde 1 hour after bromodeoxyuridine injection. The brains were processed, and frozen sections were obtained. Sections through transplant tissue were analyzed using immunohistochemistry and compared with normal olfactory epithelium. Results Graft survival approached 85% with mature olfactory neurons detected in 35% of the transplants stained for olfactory marker protein. Transplant epithelium resembled normal olfactory epithelium containing mature olfactory neurons and axon bundles. Conclusions Studies of olfactory neuron regeneration have been limited by the inability to produce cultures with long-term viability. Olfactory epithelial grafts to the cerebral cortex provide an alternative approach to the study of olfactory neuron regeneration. PMID:11801979

  8. Esophageal trichomoniasis in chickens.

    PubMed

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

    1995-01-01

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

  9. Hypnotherapy for Esophageal Disorders.

    PubMed

    Riehl, Megan E; Keefer, Laurie

    2015-07-01

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

  10. [Eosinophilic esophagitis: an "emerging disease"].

    PubMed

    Collardeau-Frachon, Sophie; Hervieu, Valérie; Scoazec, Jean-Yves

    2007-12-01

    Eosinophilic esophagitis is a recently identified disease. The histological examination of esophageal biopsies is essential for its diagnosis, which is made with steadily increasing frequency. Eosinophilic esophagitis is an anatomoclinical entity, involving both children and adults, characterized by a dense and isolated infiltration of the esophageal mucosa by eosinophils, revealed by clinical symptoms of upper digestive tract origin and resistant to anti-acid treatment with IPP at high doses. Eosinophilic esophagitis is currently interpreted as an allergic disease, even though its pathogenesis remains unclear. The disease has a chronic course with persistent or relapsing symptoms, present with symptoms similar to those of gastro-esophageal reflux or with dysphagia. Endoscopic examination shows the presence of characteristic, but not pathognomonic, lesions (stenoses, strictures, circular rings, reduction of calibre, white specks, granularity of the mucosa). The histological diagnosis requires multiple biopsies taken all along the esophagus. The main sign is the presence of a dense eosinophilic infiltrate of the mucosa: a peak density of more than 15 eosinophils in at least one x400 field is the minimal criteria required for diagnosis. Associated lesions correspond to tissue damage and repair secondary to eosinophil activation (basal hyperplasia, microabscesses, fibrosis of the lamina propria). The treatment is based on dietary measures (allergen exclusion) and on the use of anti-inflammatory drugs, mainly corticoids. In conclusion, eosinophilic esophagitis is an emerging disease, important to identify, since it requires a specific treatment, different from that of reflux esophagitis. PMID:18554551

  11. Esophageal Manifestations of Multisystem Diseases

    PubMed Central

    Mapp, Esmond

    1980-01-01

    The esophagus may be involved directly or indirectly by numerous disease conditions. On occasion, the esophageal process may be the key to the diagnosis. In some situations, the esophageal manifestation of a disease may be more immediately life-threatening than the primary process. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:7310903

  12. Cells of origin of squamous epithelium, dysplasia and cancer in the head and neck region after bone marrow transplantation.

    PubMed

    Kano, Yoshihiro; Ishii, Hideshi; Konno, Masamitsu; Yamasaki, Makoto; Miyata, Hiroshi; Nishikawa, Shimpei; Hamabe, Atsushi; Ogawa, Hisataka; Takahashi, Hidekazu; Ohta, Katsuya; Hasegawa, Shinichiro; Tanaka, Kouji; Fukusumi, Takahito; Otsuka, Masahisa; Kawamoto, Koichi; Haraguchi, Naotsugu; Fujimoto, Rika; Isobe, Masaharu; Tomita, Yasuhiko; Matsuura, Nariaki; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2014-02-01

    Secondary solid tumors that occur after hematopoietic stem cell transplantation (HSCT) are late complications of HSCT. Previously, secondary solid tumors were considered to be recipient-derived cells because transplanted cells do not contain epithelial cells. Recently, however, not only donor‑derived epithelial cells but also donor-derived secondary solid tumors have also been reported in mice and humans. It means that circulating bone marrow-derived stem cells (BMDCs) including hematopoietic stem cells include the stem cells of many tissue types and the precancerous cells of many solid tumors. In most reports of donor-derived secondary solid tumors, however, tumors contained a low proportion of BMDC-derived epithelial cells in mixed solid tumor tissues. To our knowledge, there are only five known cases of completely donor-derived tumor tissues, i.e., four oral SCCs and a pharyngeal SCC. In this study, we analyzed five human clinical samples of solid tumors, i.e., two esophageal squamous cell carcinomas (SCCs), two oral SCCs and a tongue carcinoma. In the oral and tongue, completely donor-derived tissues were not observed, but in esophagus a completely donor-derived esophageal epidermis and SCC were observed for the first time. In addition, in another esophageal SCC patient, a completely donor-derived dysplasia region of esophageal epidermis was observed near recipient-derived SCC. This study suggests that BMDC-derived cells include the stem cells of esophageal epidermis and the precancerous cells of esophageal SCC and can differentiate into esophageal epithelium and esophageal SCC. PMID:24317739

  13. [Endoscopic Therapy for Esophageal Cancer].

    PubMed

    Sakai, Makoto; Kuwano, Hiroyuki

    2016-07-01

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

  14. Eosinophilic Esophagitis: Biology to Therapy

    PubMed Central

    Rothenberg, Marc E.

    2014-01-01

    Eosinophilic esophagitis, a recently recognized and growing clinical disorder over the past decade, is characterized by antigen-driven eosinophil accumulation in the esophagus. Symptoms frequently mimic those of gastroesophageal reflux disease (GERD) but the two diseases are quite distinct in terms of their histopathology, genetic signature, response to therapy, hereditary risk and association with allergy. Disease pathogenesis involves the interplay of external and genetic factors, particularly food antigens and the eosinophil chemoattractant eotaxin-3, respectively. Transcript signatures and animal models have uncovered the importance of adaptive T cell immunity involving IL-5 and IL-13 elicited esophageal epithelial cell responses. Notably, symptoms, dysregulated esophageal gene expression and pathology are largely reversible following reduction of specific food antigen exposure, as well as anti-inflammatory therapy, but chronic treatment is necessary to prevent relapse. As such, eosinophilic esophagitis is a disease with the unique features of chronic esophagitis, atopy, immune sensitization to oral antigens, reversibility and familial association. PMID:19596009

  15. Characterization of side population cells from human airway epithelium.

    PubMed

    Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V; Jacoby, David B; Kicic, Anthony; Stick, Stephen M; Knight, Darryl A

    2008-10-01

    The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45(-) SP, CD45(+) SP, and non-SP cells were isolated and sorted. CD45(-) SP cells made up 0.12% +/- 0.01% of the total epithelial cell population in normal airway but 4.1% +/- 0.06% of the epithelium in asthmatic airways. All CD45(-) SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45(-) SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45(-) SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and long-term proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium. Disclosure of potential conflicts of interest is found at the end of this article. PMID:18653771

  16. Cell proliferation in the human gallbladder epithelium: effect of distension.

    PubMed Central

    Putz, P; Willems, G

    1979-01-01

    DNA synthesis activity in the epithelium of the human gallbladder was studied through in vitro labelling of mucosal specimens with 3H-thymidine and autoradiography. The specimens were taken at the time of a surgical operation. Eight 'normal' gallbladders and six distended gallbladders from patients with carcinomatous obstruction of the common bile duct were examined. Proliferative activity was very low in the normal and significantly higher in the distended gallbladders. Images Figure PMID:437558

  17. 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 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

  18. Omeprazole in infants with cimetidine-resistant peptic esophagitis.

    PubMed

    Alliët, P; Raes, M; Bruneel, E; Gillis, P

    1998-02-01

    Twelve neurologically normal infants (age 2.9+/-0.9 months) with peptic esophagitis (grade 2) who did not respond to cimetidine (in addition to positioning, cisapride, and Gaviscon) were treated with omeprazole, 0.5 mg/kg once a day, for 6 weeks. The effectiveness of omeprazole was evaluated in all infants by clinical assessment and endoscopy before and after treatment and by 24-hour gastric pH monitoring during treatment in seven infants. Omeprazole therapy led to a marked decrease in symptoms, endoscopic and histologic signs of esophagitis, and intragastric acidity. PMID:9506656

  19. Radionuclide transit: a sensitive screening test for esophageal dysfunction

    SciTech Connect

    Russell, C.O.; Hill, L.D.; Holmes, E.R. III; Hull, D.A.; Gannon, R.; Pope, C.E. II

    1981-05-01

    The purpose of this study was to extend existing nuclear medicine techniques for the diagnosis of esophageal motor disorders. A standard homogeneous bolus of 99mtechnetium sulfur colloid in water was swallowed in the supine position under the collimator of a gamma camera linked to a microprocessor. Bolus transit was recorded at 0.4-s intervals, and the movie obtained was used to analyze transit in an objective manner. Ten normal volunteers and 30 subjects with dysphagia not related to mechanical obstruction were studied with this technique. Radionuclide transit studies detected a higher incidence of esophageal motor abnormality than manometry or radiology in the dysphagia group. In addition a definitive description of the functional problem was possible in most cases. Radionuclide transit is a safe noninvasive test and suitable as a screening test for esophageal motor disorders.

  20. Esophageal replacement in children: Challenges and long-term outcomes

    PubMed Central

    Soccorso, Giampiero; Parikh, Dakshesh H.

    2016-01-01

    Replacement of a nonexistent or damaged esophagus continues to pose a significant challenge to pediatric surgeons. Various esophageal replacement grafts and techniques have not produced consistently good outcomes to emulate normal esophagus. Therefore, many techniques are still being practiced and recommended with no clear consensus. We present a concise literature review of the currently used techniques and with discussions on the advantages and anticipated morbidity. There are no randomized controlled pediatric studies to compare different types of esophageal replacements. Management and graft choice are based on geographical and personal predilections rather than on any discernible objective data. The biggest series with long-term outcome are reported for gastric transposition and colonic replacement. Comparison of different studies shows no significant difference in early (graft necrosis and anastomotic leaks) or late complications (strictures, poor feeding, gastro-esophageal reflux, tortuosity of the graft, and Barrett's esophagus). The biggest series seem to have lower complications than small series reflecting the decennials experience in their respective centers. Long-term follow-up is recommended following esophageal replacement for the development of late strictures, excessive tortuosity, and Barrett's changes within the graft. Once child overcomes initial morbidity and establishes oral feeding, long-term consequences and complications of pediatric esophageal replacement should be monitored and managed in adult life. PMID:27365900

  1. Markers of tyrosine kinase activity in eosinophilic esophagitis: A pilot study of the FIP1L1-PDGFRα fusion gene, pERK 1/2, and pSTAT5

    PubMed Central

    Dellon, Evan S.; Bower, Jacquelyn J.; Keku, Temitope O.; Chen, Xiaoxin; Miller, C. Ryan; Woosley, John T.; Orlando, Roy C.; Shaheen, Nicholas J.

    2011-01-01

    Background and Aims The pathogenesis of eosinophilic esophagitis (EoE) is incompletely understood. In certain eosinophilic diseases, activation of tyrosine kinase after fusion of the Fip1-like-1 and platelet-derived growth factor receptor-α genes (F-P fusion gene) mediates eosinophilia via downstream effectors such as extracellular-regulated kinase (ERK1/2) and signal transducers and activators of transcription (STAT5). This mechanism has not been examined in EoE. Our aim was to detect the F-P fusion gene, pERK1/2, and pSTAT5 in esophageal tissue from patients with EoE, gastroesophageal reflux disease (GERD), and normal controls. Materials and Methods We performed a cross-sectional pilot study comparing patients with steroid-responsive and steroid-refractory EoE, to GERD patients and normal controls. EoE cases were defined by consensus guidelines. Fluorescence in-situ hybridization (FISH) was performed to detect the F-P fusion gene and immunohistochemistry (IHC) was performed to detect pERK1/2 and pSTAT5 in esophageal biopsies. Results Twenty-nine subjects (median age 30 yrs (range 1–59); 16 male; 24 Caucasian) were included: 8 normal, 6 GERD, and 15 EoE (5 steroid-refractory). On FISH, 98%, 99%, and 99% of the nuclei in the normal, GERD, and EoE groups, respectively, were normal (p=0.42). On IHC, a median of 250, 277, and 479 nuclei/mm2 stained for pERK1/2 in the normal, GERD, and EoE groups, respectively (p=0.07); the refractory EoE patients had the highest degree pERK1/2 staining (846 nuclei/mm2; p=0.07). No trend was seen for pSTAT5. Conclusions The F-P fusion gene was not detected with increased frequency in EoE. Patients with EoE had a trend towards higher levels of pERK1/2, but not STAT5, in the esophageal epithelium, with highest levels in steroid-refractory EoE patients. PMID:21819482

  2. 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

  3. Esophageal Lipoma: A Rare Tumor

    PubMed Central

    Feldman, Jeremy; Tejerina, Manfred; Hallowell, Michael

    2012-01-01

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

  4. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

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

  5. 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.

  6. Mechanisms of airway responses to esophageal acidification in cats.

    PubMed

    Lang, Ivan M; Haworth, Steven T; Medda, Bidyut K; Forster, Hubert; Shaker, Reza

    2016-04-01

    Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats (n = 72), we investigated the effects of vagotomy or atropine (100 μg·kg(-1)·30 min(-1) iv) on airway responses to esophageal infusion of 0.1 M PBS or 0.1 N HCl at 1 ml/min. We quantified 1) diameter of the bronchi, 2) tracheobronchial mucociliary transport rate, 3) tracheobronchial mucous secretion, and 4) mucous content of the tracheal epithelium and submucosa. We found that vagotomy or atropine blocked the airway constriction response but only atropine blocked the increase in mucous output and decrease in mucociliary transport rate caused by esophageal acidification. The mucous cells of the mucosa produced more Alcian blue- than periodic acid-Schiff (PAS)-stained mucosubstances, and the mucous cells of the submucosa produced more PAS- than Alcian blue-stained mucosubstances. Selective perfusion of the different segments of esophagus with HCl or PBS resulted in significantly greater production of PAS-stained mucus in the submucosa of the trachea adjacent to the HCl-perfused esophagus than in that adjacent to the PBS-perfused esophagus. In conclusion, airway constriction caused by esophageal acidification is mediated by a vagal cholinergic pathway, and the tracheobronchial transport response is mediated by cholinergic receptors. Acid perfusion of the esophagus selectively increases production of neutral mucosubstances of the apocrine glands by a local mechanism. We hypothesize that the airway responses to esophageal acid exposure are part of the innate, rather than acute emergency, airway defense system. PMID:26846551

  7. Relevance of N-nitrosamines to esophageal cancer in China

    SciTech Connect

    Lu, S.H.; Montesano, R.; Zhang, M.S.; Feng, L.; Luo, F.J.; Chui, S.X.; Umbenhauer, D.; Saffhill, R.; Rajewsky, M.F.

    1986-01-01

    Studies on the relevance of the N-nitrosamines to esophageal cancer in China are reviewed. Although a causal association between nitrosamines exposure and esophageal cancer in China has not yet been rigorously established, exposure of Lin-Xian subjects to nitrosamines either directly or as a result of their in vivo formation has been detected in our study. Several N-nitrosamines (NDMA, NDEA, NMBzA, NPyr, NPip, and NSAR) in gastric juice collected from Lin-Xian inhabitants have been detected. A correlation was found between the lesions of esophageal epithelium and the amount of nitrosamines present. In addition, the amounts of N-nitrosamino acids excreted in 24-hr urine of subjects in Lin-Xian were significantly higher than those in Fan-Xian, indicating a higher exposure to N-nitroso compound and their precursors of the inhabitants in the high-risk area. The effect of nitrosamines on human esophagus has been investigated at the cellular levels. The amounts of O/sup 6/-MedG in DNA of esophageal or stomach mucosa of patients from Lin-Xian were higher than that from Europe. The presence of O/sup 6/-MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O/sup 6/-MedG in esophageal DNA could be the result of a recent exposure to N-nitroso compounds or a genetically determined reduced cellular capacity for repair of O/sup 6/-MedG from DNA. The hyperplasia was induced in the esophagus of human fetus that cultured with NMBzA for 2 weeks to 2 months. The intervention studies of esophageal cancer in Lin-Xian have been pursued. Intake of moderate doses of ascorbic acids by Lin-Xian subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in the low-risk area.

  8. Neuropilins: expression and roles in the epithelium.

    PubMed

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

    2012-04-01

    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 NRP's 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

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

    PubMed Central

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

    2013-01-01

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

  10. Characterizing the inflammatory response in esophageal mucosal biopsies in children with eosinophilic esophagitis.

    PubMed

    Sayej, Wael N; Ménoret, Antoine; Maharjan, Anu S; Fernandez, Marina; Wang, Zhu; Balarezo, Fabiola; Hyams, Jeffrey S; Sylvester, Francisco A; Vella, Anthony T

    2016-07-01

    Eosinophilic esophagitis (EoE) is an emerging allergic, IgE- and non-IgE (Th2 cell)-mediated disease. There are major gaps in the understanding of the basic mechanisms that drive the persistence of EoE. We investigated whether esophageal biopsies from children with EoE demonstrate an inflammatory response that is distinct from normal controls. We prospectively enrolled 84 patients, of whom 77 were included in our analysis, aged 4-17 years (12.8±3.8 years; 81% males). Five esophageal biopsies were collected from each patient at the time of endoscopy. Intramucosal lymphocytes were isolated, phenotyped and stimulated with phorbol 12-myristate 13-acetate/ionomycin to measure their potential to produce cytokines via flow cytometry. We also performed cytokine arrays on 72-h biopsy culture supernatants. CD8(+) T cells, compared with CD4(+) T cells, synthesized more TNF-α and interferon (IFN)-γ after mitogen stimulation in the EoE-New/Active vs EoE-Remission group (P=0.0098; P=0.02) and controls (P=0.0008; P=0.03). Culture supernatants taken from explant esophageal tissue contained 13 analytes that distinguished EoE-New/Active from EoE-Remission and Controls. Principal component analysis and cluster analysis based on these analytes distinctly separated EoE-New/Active from EoE-Remission and Controls. In summary, we have identified a previously unappreciated role for CD8(+) T lymphocytes with potential to produce TNF-α and IFN-γ in EoE. Our results suggest that CD8(+) T cells have a role in the persistence or progression of EoE. We have also identified a panel of analytes produced by intact esophageal biopsies that differentiates EoE-New/Active from EoE-Remission and controls. Our results suggest that esophageal epithelial cells may have specific immune effector functions in EoE that control the type and amplitude of inflammation. PMID:27525061

  11. Characterizing the inflammatory response in esophageal mucosal biopsies in children with eosinophilic esophagitis

    PubMed Central

    Sayej, Wael N; Ménoret, Antoine; Maharjan, Anu S; Fernandez, Marina; Wang, Zhu; Balarezo, Fabiola; Hyams, Jeffrey S; Sylvester, Francisco A; Vella, Anthony T

    2016-01-01

    Eosinophilic esophagitis (EoE) is an emerging allergic, IgE- and non-IgE (Th2 cell)-mediated disease. There are major gaps in the understanding of the basic mechanisms that drive the persistence of EoE. We investigated whether esophageal biopsies from children with EoE demonstrate an inflammatory response that is distinct from normal controls. We prospectively enrolled 84 patients, of whom 77 were included in our analysis, aged 4–17 years (12.8±3.8 years; 81% males). Five esophageal biopsies were collected from each patient at the time of endoscopy. Intramucosal lymphocytes were isolated, phenotyped and stimulated with phorbol 12-myristate 13-acetate/ionomycin to measure their potential to produce cytokines via flow cytometry. We also performed cytokine arrays on 72-h biopsy culture supernatants. CD8+ T cells, compared with CD4+ T cells, synthesized more TNF-α and interferon (IFN)-γ after mitogen stimulation in the EoE-New/Active vs EoE-Remission group (P=0.0098; P=0.02) and controls (P=0.0008; P=0.03). Culture supernatants taken from explant esophageal tissue contained 13 analytes that distinguished EoE-New/Active from EoE-Remission and Controls. Principal component analysis and cluster analysis based on these analytes distinctly separated EoE-New/Active from EoE-Remission and Controls. In summary, we have identified a previously unappreciated role for CD8+ T lymphocytes with potential to produce TNF-α and IFN-γ in EoE. Our results suggest that CD8+ T cells have a role in the persistence or progression of EoE. We have also identified a panel of analytes produced by intact esophageal biopsies that differentiates EoE-New/Active from EoE-Remission and controls. Our results suggest that esophageal epithelial cells may have specific immune effector functions in EoE that control the type and amplitude of inflammation. PMID:27525061

  12. Heat treatment of human esophageal tissues: Effect on esophageal cancer detection using oxygenated hemoglobin diffuse reflectance ratio

    NASA Astrophysics Data System (ADS)

    Zhao, Q. L.; Guo, Z. Y.; Si, J. L.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Guo, X.; Zhong, H. Q.; Li, L. Q.; Li, X. Y.

    2011-03-01

    The main objective of the present work is to study the influence of heat treatment on the esophageal cancer detection using the diffuse reflectance (DR) spectral intensity ratio R540/R575 of oxygenated hemoglobin (HbO2) absorption bands to distinguish the epithelial tissues of normal human esophagus and moderately differentiated esophageal squamous cell carcinoma (ESCC) at different heat treatment temperature of 20, 37, 42, 50, and 60°C, respectively. The DR spectra for the epithelial tissues of the normal esophagus and ESCC in vitro at different heat-treatment temperature in the wavelength range 400-650 nm were measured with a commercial optical fiber spectrometer. The results indicate that the average DR spectral intensity overall enhancement with concomitant increase of heat-treatment temperature for the epithelial tissues of normal esophagus and ESCC, but the average DR spectral intensity for the normal esophageal epithelial tissues is relatively higher than that for ESCC epithelial tissues at the same heat-treatment temperature. The mean R540/R575 ratios of ESCC epithelial tissues were always lower than that of normal esophageal epithelial tissues at the same temperature, and the mean R540/R575 ratios of the epithelial tissues of the normal esophagus and ESCC were decreasing with the increase of different heat-treatment temperatures. The differences in the mean R540/R575 ratios between the epithelial tissues of normal esophagus and ESCC were 13.33, 13.59, 11.76, and 11.11% at different heat-treatment temperature of 20, 37, 42, and 50°C, respectively. These results also indicate that the DR intensity ratio R540/R575 of the hemoglobin bands is a useful tool for discrimination between the epithelial tissues of normal esophagus and ESCC in the temperature range from room temperature to 50°C, but it was non-effective at 60°C or over 60°C.

  13. Environmental Causes of Esophageal Cancer

    PubMed Central

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

    2009-01-01

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

  14. 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.

  15. Caustic ingestion and esophageal function

    SciTech Connect

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

    1990-02-01

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

  16. Uses of esophageal function testing: dysphagia.

    PubMed

    Yazaki, Etsuro; Woodland, Philip; Sifrim, Daniel

    2014-10-01

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

  17. 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

  18. 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

  19. Cloxacillin: A New Cause of Pill-Induced Esophagitis

    PubMed Central

    Zezos, Petros; Harel, Ziv; Saibil, Fred

    2016-01-01

    A large variety of medications can cause pill-induced esophagitis. Herein we present a case of cloxacillin-induced esophagitis. A 66-year-old male presented with an acute onset of epigastric and retrosternal pain on the 5th day of a course of oral cloxacillin prescribed for erysipelas. Initial clinical and imaging assessment was negative and he was sent home. A few days later, he returned with persistent severe retrosternal pain; endoscopy at the same day revealed a normal upper esophagus, several small stellate erosions in the midesophagus, and a normal squamocolumnar junction with a small hiatus hernia. Treatment with esomeprazole 40 mg bid and MucaineR suspension resulted in complete resolution of his symptoms. Pill-induced esophagitis may be underreported by patients, when symptoms are mild and unrecognized and/or underdiagnosed by the clinicians as a cause of retrosternal pain, odynophagia, or dysphagia. Failure of early recognition may result in unnecessary diagnostic investigations and prolongation of the patient's discomfort. This case signifies the importance of enhancing clinician awareness for drug-associated esophageal injury when assessing patients with retrosternal pain, as well as the value of prophylaxis against this unpleasant condition by universally recommending drinking enough water in an upright position during ingestion of any oral medication. PMID:27446834

  20. Cervical esophageal dysphagia: indications for and results of cricopharyngeal myotomy.

    PubMed Central

    Ellis, F H; Crozier, R E

    1981-01-01

    Twenty patients with cervical esophageal dysphagia were treated by cricopharyngeal myotomy. Of these 20 patients, ten had pharyngoesophageal diverticula, four had a hypertensive upper esophageal sphincter (UES), four had bulbar palsy, and two has miscellaneous forms of cricopharyngeal dysfunction. Preoperative esophageal manometric examination revealed mean UES pressures of 37.2 mmHg +/- 4.8 SEM in patients with diverticula-markedly lower (p = 0.01) than in normal patients (55.9 mmHg +/- 5.0 SEM). In patients with hypertensive UES the mean pressure was 166.2 mmHg +/- 13.4, significantly higher (p less than 0.001) than normal. Incoordination of the deglutitive response of the UES characterised by premature relaxation and contraction was present in all patients with diverticula and in one other patient. Another patient exhibited incomplete sphincteric relaxation (achalasia). A 4-5 cm myotomy of the cricopharyngeus muscle and adjacent esophageal muscle was performed in all patients. On the patients with diverticula two also had diverticulectomy. No patient with bulbar palsy was benefited. All other patients were relieved of dysphagia by the operation, with the exception of one patient with a diverticulum. A subsequent diverticulectomy was required in this patient. Postoperative manometric examination revealed an average decrease in UES pressure of 63% and an average decreased in length of the high pressure zone of 1.4 cm. Images Fig. 1. Fig. 2. Fig. 3. Fig. 6. Fig. 7. Fig. 8. PMID:6791598

  1. Esophageal space-occupying lesion caused by Ascaris lumbricoides.

    PubMed

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

    2012-04-01

    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 patient's 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

  2. 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

  3. Effect of peroral esophageal myotomy for achalasia treatment: A Chinese study

    PubMed Central

    Lu, Bin; Li, Meng; Hu, Yue; Xu, Yi; Zhang, Shuo; Cai, Li-Jun

    2015-01-01

    AIM: To assess the safety and feasibility of peroral esophageal myotomy (POEM) in patients with achalasia. METHODS: From January 2012 to March 2014, 50 patients (28 men, 22 women; mean age: 42.8 years, range: 14-70 years) underwent POEM. Pre- and postoperative symptoms were quantified using the Eckardt scoring system. Barium swallow and esophagogastroscopy were performed before and after POEM, respectively. Esophageal motility was evaluated in all patients, both preoperatively and one month after POEM treatment, using a high-resolution manometry system. Manometry data, Eckardt scores, lower esophageal sphincter pressure and barium swallow results were used to evaluate the effect of the procedure. RESULTS: POEM was successfully completed for all patients. The mean procedure time was 55.4 ± 17.3 min and the mean total length of myotomy of the circular esophagus was 10.5 ± 2.6 cm. No specific complications occurred, with the exception of two patients that developed asymptomatic pneumomediastinum and subcutaneous emphysema. Clinical improvement in symptoms was achieved in all patients. Approximately 77.5% of patients experienced weight gain 6 mo after POEM, with an average of 4.78 kg (range: 2-15 kg). The lower esophageal sphincter resting pressure, four second integrated relaxation pressure and Eckardt scores were all significantly reduced after POEM (Ps < 0.05). A small segment of proximal esophageal peristalsis appeared postoperatively in two patients, but without normal esophageal peristalsis. The average diameter of the esophageal lumen decreased significantly from 4.39 to 3.09 cm (P < 0.01). CONCLUSION: POEM can relieve achalasia symptoms, improve gastroesophageal junction relaxation and restore esophageal body motility function, but not normal esophageal peristalsis. PMID:25987787

  4. 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.

  5. Protease-activated receptor (PAR)1, PAR2 and PAR4 expressions in esophageal squamous cell carcinoma

    PubMed Central

    LI, Si-Man; JIANG, Ping; XIANG, Yang; WANG, Wei-Wei; ZHU, Yue-Chun; FENG, Wei-Yang; LI, Shu-De; YU, Guo-Yu

    2014-01-01

    Here, we used reverse transcription-PCR (RT-PCR) and western blot to detect protease-activated receptor (PAR) 1, PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma, and investigated the co-relationship between PAR expression and clinic-pathological data for esophageal cancer. The methylation of PAR4 gene promoter involved in esophageal carcinoma was also analyzed. By comparing the mRNA expressions of normal esophageal tissue and human esophageal epithelial cells (HEEpiC), we found that among the 28 cases of esophageal squamous cell carcinoma, PAR1 (60%) and PAR2 (71%) were elevated in 17 and 20 cases, respectively, and PAR4 (68%) expression was lowered in 19 cases. Whereas, in human esophageal squamous cells (TE-1 and TE-10), PAR1 and PAR2 expression was increased but PAR4 was decreased. Combined with clinical data, the expression of PAR1 in poorly differentiated (P=0.016) and middle and lower parts of the esophagus (P=0.016) was higher; expression of PAR4 in poorly differentiated carcinoma was lower (P=0.049). Regarding TE-1 and TE-10 protein expression, we found that in randomized esophageal carcinoma, PAR1 (P=0.027) and PAR2 (P=0.039) expressions were increased, but lowered for PAR4 (P=0.0001). In HEEpiC, TE-1, TE-10, esophageal and normal esophagus tissue samples (case No. 7), the frequency of methylation at the 19 CpG loci of PAR4 was 35.4%, 95.2%, 83.8%, 62.6% and 48.2%, respectively. Our results indicate that the expression of PAR1 and PAR2 in esophageal squamous cell carcinoma is increased but PAR4 is decreased. Hypermethylation of the promoter of the PAR4 gene may contribute to reduced expression of PAR4 in esophageal squamous cell carcinoma. PMID:25297082

  6. Eosinophilic Esophagitis in Pediatric and Adolescent Patients

    MedlinePlus

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

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. Suppression of esophageal tumor growth and chemoresistance by directly targeting the PI3K/AKT pathway.

    PubMed

    Li, Bin; Li, Jin; Xu, Wen Wen; Guan, Xin Yuan; Qin, Yan Ru; Zhang, Li Yi; Law, Simon; Tsao, Sai Wah; Cheung, Annie L M

    2014-11-30

    Esophageal cancer is the sixth most common cause of cancer-related deaths worldwide. Novel therapeutic intervention is urgently needed for this deadly disease. The functional role of PI3K/AKT pathway in esophageal cancer is little known. In this study, our results from 49 pairs of human esophageal tumor and normal specimens demonstrated that AKT was constitutively active in the majority (75.5%) of esophageal tumors compared with corresponding normal tissues. Inhibition of the PI3K/AKT pathway with specific inhibitors, wortmannin and LY294002, significantly reduced Bcl-xL expression, induced caspase-3-dependent apoptosis, and repressed cell proliferation and tumor growth in vitro and in vivo without obvious toxic effects. Moreover, significantly higher expression level of p-AKT was observed in fluorouracil (5-FU)-resistant esophageal cancer cells. Inactivation of PI3K/AKT pathway markedly increased the sensitivity and even reversed acquired resistance of esophageal cancer cells to chemotherapeutic drugs in vitro. More importantly, the resistance of tumor xenografts derived from esophageal cancer cells with acquired 5-FU resistance to chemotherapeutic drugs was significantly abrogated by wortmannin treatment in animals. In summary, our data support PI3K/AKT as a valid therapeutic target and strongly suggest that PI3K/AKT inhibitors used in conjunction with conventional chemotherapy may be a potentially useful therapeutic strategy in treating esophageal cancer patients. PMID:25344912

  12. 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 (0–3 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

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

    PubMed Central

    Wen, Jing; Lu, Zhongsheng; Liu, Qingsen

    2014-01-01

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

  14. 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 Barrett’s esophagus (BE), which is represented by metaplasia-dysplasia-carcinoma transition, is regarded as the premalignant lesion of esophageal neoplasm. However, our knowledge about the development of esophageal adenocarcinoma is still very limited. Material/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

  15. Investigation of Esophageal Sensation and Biomechanical Properties in Functional Chest Pain

    PubMed Central

    Nasr, Issam; Attaluri, Ashok; Hashmi, Syed; Gregersen, Hans; Rao, Satish S.C.

    2010-01-01

    OBJECTIVES There is limited and conflicting data regarding the role of esophageal hypersensitivity in the pathogenesis of functional chest pain (FCP). We examined esophageal sensori-motor properties, mechanics and symptoms in subjects with FCP. METHODS Esophageal balloon distension test (EBDT) was performed using impedance planimetry in 189 (m/f = 57/132) consecutive subjects with noncardiac, non-reflux chest pain, and 36 (m/f = 16/20) healthy controls. The biomechanical and sensory properties of subjects with and without esophageal hypersensitivity were compared to controls. The frequency, intensity and duration of chest pain were assessed. RESULTS: 143 (75 %) subjects had esophageal hypersensitivity and 46 (25%) had normal sensitivity. Typical chest pain was reproduced in 105/143 (74%) subjects. Subjects with hypersensitivity demonstrated larger cross-sectional area (CSA) (p<0.001), decreased esophageal wall strain (p<0.001) and distensibility (p<0.001), and lower thresholds for perception (p<0.01), discomfort (p<0.01) and pain (p<0.01) compared to those without hypersensitivity or healthy controls. Chest pain scores (mean ± SD) for frequency, intensity and duration were 2.5 ± 0.3, 2.2 ± 0.2 and 2.2 ± 0.2 respectively, and were similar between the two patient groups. CONCLUSIONS 75% of subjects with FCP demonstrate esophageal hypersensitivity. Visceral hyperalgesia and sensori-motor dysfunction of the esophagus play a key role in the pathogenesis of chest pain. PMID:20067548

  16. Velocity fields in a collectively migrating epithelium.

    PubMed

    Petitjean, L; Reffay, M; Grasland-Mongrain, E; Poujade, M; Ladoux, B; Buguin, A; Silberzan, P

    2010-05-19

    We report quantitative measurements of the velocity field of collectively migrating cells in a motile epithelium. The migration is triggered by presenting free surface to an initially confluent monolayer by using a microstencil technique that does not damage the cells. To avoid the technical difficulties inherent in the tracking of single cells, the field is mapped using the technique of particle image velocimetry. The main relevant parameters, such as the velocity module, the order parameter, and the velocity correlation function, are then extracted from this cartography. These quantities are dynamically measured on two types of cells (collectively migrating Madin-Darby canine kidney (MDCK) cells and fibroblastlike normal rat kidney (NRK) cells), first as they approach confluence, and then when the geometrical constraints are released. In particular, for MDCK cells filling up the patterns, we observe a sharp decrease in the average velocity after the point of confluence, whereas the densification of the monolayer is much more regular. After the peeling off of the stencil, a velocity correlation length of approximately 200 microm is measured for MDCK cells versus only approximately 40 microm for the more independent NRK cells. Our conclusions are supported by parallel single-cell tracking experiments. By using the biorthogonal decomposition of the velocity field, we conclude that the velocity field of MDCK cells is very coherent in contrast with the NRK cells. The displacements in the fingers arising from the border of MDCK epithelia are very oriented along their main direction. They influence the velocity field in the epithelium over a distance of approximately 200 microm. PMID:20441742

  17. Gallium-67 imaging in candidal esophagitis

    SciTech Connect

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

    1990-01-01

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

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

    PubMed

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

    2013-10-01

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

  19. 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.

  20. Esophageal cancer stem cells and implications for future therapeutics

    PubMed Central

    Qian, Xia; Tan, Cheng; Wang, Feng; Yang, Baixia; Ge, Yangyang; Guan, Zhifeng; Cai, Jing

    2016-01-01

    Esophageal carcinoma (EC) is a lethal disease with high morbidity and mortality worldwide, and the incidence has been increasing in recent years. Although the diagnosis and treatment of EC have improved considerably, EC has rapidly progressed in the clinical setting and has a poor prognosis for its metastasis and recurrence. The general idea of cancer stem cells (CSCs) is primarily based on clinical and experimental observations, indicating the existence of a subpopulation of cells that can self-renew and differentiate. The EC stem cells, which can be isolated from normal pluripotent stem cells by applying similar biomarkers, may participate in promoting esophageal tumorigenesis through renewal and repair. In this review, major emphasis is given to CSC markers, altered CSC-specific pathways, and molecular targeting agents currently available to target CSCs of esophageal cancer. The roles of numerous markers (CD44, aldehyde dehydrogenase, CD133, and ATP-binding cassette subfamily G member 2) and developmental signaling pathways (Wnt/β-catenin, Notch, hedgehog, and Hippo) in isolating esophageal CSCs are discussed in detail. Targeting CSCs can be a logical strategy to treat EC, as these cells are responsible for carcinoma recurrence and chemoradiation resistance. PMID:27143920

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

    PubMed

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

    2016-03-01

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

  2. 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

  3. Surgical treatments for esophageal cancers

    PubMed Central

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

    2015-01-01

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

  4. Neoadjuvant treatment of esophageal cancer

    PubMed Central

    Campbell, Nicholas P; Villaflor, Victoria M

    2010-01-01

    The management of esophageal cancer has been evolving over the past 30 years. In the United States, multimodality treatment combining chemotherapy and radiotherapy (RT) prior to surgical resection has come to be accepted by many as the standard of care, although debate about its overall effect on survival still exists, and rightfully so. Despite recent improvements in detection and treatment, the overall survival of patients with esophageal cancer remains lower than most solid tumors, which highlights why further advances are so desperately needed. The aim of this article is to provide a complete review of the history of esophageal cancer treatment with the addition of chemotherapy, RT, and more recently, targeted agents to the surgical management of resectable disease. PMID:20698042

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

    PubMed Central

    Truskaite, Kotryna

    2016-01-01

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

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

    PubMed

    Truskaite, Kotryna; Dlugosz, Aldona

    2016-01-01

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

  7. Reslizumab for pediatric eosinophilic esophagitis.

    PubMed

    Walsh, Garry M

    2010-07-01

    Pediatric eosinophilic esophagitis is an inflammatory condition associated with marked eosinophil accumulation in the mucosal tissues of the esophagus. Eosinophils are major proinflammatory cells thought to make a major contribution to allergic diseases that affect the upper and lower airways, skin and GI tract. IL-5 is central to eosinophil maturation and release from the bone marrow, and their subsequent accumulation, activation and persistence in the tissues. Reslizumab (Cinquil, Ception Therapeutics Inc., PA, USA) is a humanized monoclonal antibody with potent IL-5 neutralizing effects that represents a potential treatment for eosinophilic diseases. This article considers the current status of the clinical development of reslizumab for pediatric eosinophilic esophagitis. PMID:20636000

  8. Eosinophilic esophagitis: diagnosis and management.

    PubMed

    Lieberman, Jay A; Chehade, Mirna

    2012-02-01

    Eosinophilic esophagitis is a clinicopathologic disease that can present with a constellation of upper gastrointestinal symptoms and endoscopic findings in conjunction with significant infiltration of the esophageal tissue with eosinophils. Clinical and histologic resolution of the disease can be seen with dietary restriction therapies and systemic and topical corticosteroids. Because most patients have an atopic background and the disease seems to have an underlying T-helper type 2 pathogenesis, allergists and gastroenterologists need to be familiar with the diagnosis and management of this disease. In this review, clinical characteristics, endoscopic and histologic findings, and available therapy options are discussed. PMID:22244233

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

    PubMed Central

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

    2013-01-01

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

  10. 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