Science.gov

Sample records for normal esophageal epithelium

  1. Nrf2 deficiency impairs the barrier function of mouse esophageal epithelium

    PubMed Central

    Chen, Hao; Hu, Yuhui; Fang, Yu; Djukic, Zorka; Yamamoto, Masayuki; Shaheen, Nicholas J.; Orlando, Roy C.; Chen, Xiaoxin

    2013-01-01

    Objective As a major cellular defense mechanism, the Nrf2/Keap1 pathway regulates expression of genes involved in detoxification and stress response. Our previous study revealed activation of the Nrf2/Keap1 pathway at the maturation phase during mouse esophageal development, suggesting a potential function in epithelial defense. Here we hypothesize that Nrf2 is involved in the barrier function of esophageal epithelium, and plays a protective role against gastroesophageal reflux disease (GERD). Design Human esophageal biopsy samples, mouse surgical models and Nrf2-/- mice were used to assess the role of the Nrf2/Keap1 pathway in esophageal mucosal barrier function. Trans-epithelial electrical resistance (TEER) was measured with mini-Ussing chambers. Hematoxylin and eosin (HE) staining and transmission electron microscopy were used to examine cell morphology, while gene microarray, immunohistochemistry, Western blotting and ChIP analysis were used to assess the expression of pathway genes. Results Nrf2 was expressed in normal esophageal epithelium and activated in GERD of both humans and mice. Nrf2 deficiency and gastroesophageal reflux in mice, either alone or in combination, reduced TEER and increased intercellular space diameter in esophageal epithelium. Nrf2 target genes and gene sets associated with oxidoreductase activity, mitochondrial biogenesis and energy production were down-regulated in the esophageal epithelium of Nrf2-/- mice. Consistent with the antioxidative function of Nrf2, a DNA oxidative damage marker (8OHdG) dramatically increased in esophageal epithelial cells of Nrf2-/- mice compared with those of wild-type mice. Interestingly, ATP biogenesis, Cox IV (a mitochondrial protein) and Claudin-4 (Cldn4) expression were down-regulated in the esophageal epithelium of Nrf2-/- mice, suggesting that energy-dependent tight junction integrity was subject to Nrf2 regulation. ChIP analysis confirmed the binding of Nrf2 to Cldn4 promoter. Conclusion Nrf2

  2. Esophageal epithelium of women with AIDS: thickness and local immunity.

    PubMed

    Rocha, Laura; Silva, Renata; Olegário, Janaínna; Corrêa, Rosana; Teixeira, Vicente; Cavellani, Camila

    2010-04-15

    The aim of this study was to evaluate the morphological characteristics of the esophageal epithelium (EE) and its local immunity. Esophageal fragments of autopsied women were collected from 1980 to 2008, and two groups were analyzed: with AIDS (n=17) and without AIDS (n=12). The measurement of the esophageal epithelium was carried out through the image analysis software ImageJ, and the immunostaining of Langerhans cells (LCs) was carried out using anti-S100 antibody. Women with AIDS, when compared with women without AIDS, had significantly thinner EE (220.6 versus 243.5 microm), a less number of LCs (6.2 versus 18.8 LCs/mm(2)), and a higher percentage of immature or morphologically altered LCs (66.6 versus 40.0%). The malnourished women, when compared with normonourished women, regardless of AIDS, had significantly thinner EE (227.1 versus 238.0 microm) and a less number of LCs (6.2 versus 12.5 LCs/mm(2)). The percentage of immature or morphologically altered LCs was the same in both groups. Additionally, the women with AIDS (7.0 versus 2.8%) and the malnourished women (5.8 versus 3.1%) presented a significantly higher percentage of fibrosis. We concluded that AIDS and malnutrition contribute to the decrease in esophagus local immunity and, therefore, to a possible increase in local opportunistic infections.

  3. Keratinization of the esophageal epithelium of domesticated mammals.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2013-05-01

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

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

    PubMed

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

    2006-11-01

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

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

    PubMed

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

    1981-02-01

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

  10. The ionic components of normal human oesophageal epithelium.

    PubMed

    Hopwood, D; Milne, G; Curtis, M; Nicholson, G

    1979-11-01

    The distribution of cations and anions in normal human oesophageal epithelium has been investigated with the pyroantimonate and silver-osmium tetroxide techniques. There is a discontinuous distribution of both ions in the intercellular space. The ions are associated with various organelles, as has already been described in the literature. Specifically, in the oesophageal epithelium, there are a few deposits of pyroantimonate and occasional silver in the membrane coating granules, but here is no apparent relationship of either ion with the tonofilaments or glycogen particles. The superficial cells are leaky and contain fewer ions than the deeper functional layer cells.

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

    PubMed

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

    2013-05-01

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

  12. Orthogonal arrays in normal and injured respiratory airway epithelium.

    PubMed

    Gordon, R E

    1985-02-01

    Orthogonal arrays are found on plasma membranes of glial cells, in the central nervous system, on muscle plasma membranes at neuromuscular junctions, and on a variety of epithelial cells. These structures have been correlated with ion flux. With the aid of freeze fracture technique, orthogonal particle arrays were found on plasma membranes on airway epithelial cells of rats and hamsters. They have been found in abundance at the base of secretory cells throughout normal airway epithelium. These structures were found to increase in number during regeneration in response to injury and they were found in great numbers on plasma membranes of all airway cells in response to acute and chronic NO2 exposure. The lateral and basal plasma membranes of the respiratory epithelium are a new source for studying orthogonal arrays. The normal number and distribution of these arrays can be perturbed in response to mechanical and chemical injury. PMID:3968185

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2015-01-01

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

  16. Expression of Ki-67 in normal oral epithelium, leukoplakic oral epithelium and oral squamous cell carcinoma

    PubMed Central

    Birajdar, Smita Shrishail; Radhika, MB; Paremala, K; Sudhakara, M; Soumya, M; Gadivan, Mohsin

    2014-01-01

    Aims and Objective: To demonstrate the presence, location and pattern of cell proliferation in different histological grades of oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC) and normal oral epithelium (NOE) using an antibody directed against the Ki-67 antigen and its intensity of staining evaluated respectively. Materials and Methods: A total number of 100 archival paraffin embedded blocks obtained from Department of Oral and Maxillofacial Pathology were studied. The case details were retrieved which consisted of histopathologically diagnosed cases of OSCC (n = 20), low risk OED (n = 30), high risk OED (n = 30) and normal appearing mucosa (n = 20) were taken as standard for comparison. Ki-67 immunostaining was detected. Ki-67 positive cells were counted in the five random high power fields in each case. Results: Ki-67 labeling Index (LI) was restricted to the basal and parabasal layers of the normal oral epithelium irrespective of age, sex and site whereas it was seen in the basal, suprabasal and spinous layers in OED. Ki-67 LI is increased in high risk cases than the low risk cases of OED. Ki-67 positive cells in OSCC were located in the periphery of the tumor nests than the center, where frequent mitoses were observed. Conclusion: The architectural alteration evaluated by Ki-67 antibody in proliferating cell distribution in the layers of epithelial dysplasias may provide useful information to evaluate the grading of OED. Ki-67 LI increased in high risk cases than low risk cases of OED. This study showed that over expression of Ki-67 antigen between well-differentiated and poorly differentiated OSCC was in accordance with histologic grade of malignancy but not in accordance with moderately differentiated OSCC. PMID:25328294

  17. 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

  18. [Carcinogenic and promoting effects of fish juice, preserved rice and salted dry fish on the forestomach epithelium of mice and esophageal epithelium of rats].

    PubMed

    Lin, P Z; Zhang, J S; Ding, Z W; Cai, H Y

    1986-09-01

    The carcinogenic and promoting effects of fish juice, preserved rice and salted dry fish from Nanau county, Guangdong province, a high incidence area of esophageal cancer, were studied in mice and rats. The homemade fish juice as well as fish juice in market, whether or not added with NaNO2, did not cause tumor in the forestomach of mice and the esophagus of rats. When the mice were intubated with an initiator, nitrososarcosinethylester (NSEE) twice, no carcinoma was found at the end of the experiment (D 120). Only papilloma appeared in the forestomach epithelium. The incidence was only 37.5%. However, when the mice were intubated with NSEE for 2 times followed by gastric doses of homemade fish juice, the tumor incidence in the forestomach was increased to 89.7%, in which 20.5% was carcinoma. The tumor and carcinoma incidences of initiator (NSEE and NMBzA) group and initiator + market fish juice group in mice and rats were without significant difference. The experimental results show that the homemade fish juice proved distinct promoting effect on the process of cocarcinogenesis initiated by NSEE in the forestomach of mice, while the market fish juice has no significant promoting effect on the forestomach epithelium of mice and the esophageal epithelium of rats. NSEE induced 31.6% carcinoma in the forestomach epithelium of mice on standard diet. While in mice fed with preserved rice and salted dry fish, the carcinoma incidence was increased to 63.6%. It appears that preserved rice and salted dry fish have promoting effect on the process of cocarcinogenesis initiated by NSEE in the forestomach of mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3568985

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

    PubMed

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

    2014-01-01

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

  20. Epithelium

    MedlinePlus

    The term "epithelium" refers to layers of cells that line hollow organs and glands. It is also those cells that make up the outer surface of the body. Epithelial cells help to protect or enclose organs. Most produce mucus or other secretions. Certain ...

  1. 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...

  2. Deoxycholic acid (DCA) confers an intestinal phenotype on esophageal squamous epithelium via induction of the stemness-associated reprogramming factors OCT4 and SOX2.

    PubMed

    Shen, Caifei; Zhang, Haoxiang; Wang, Pu; Feng, Ji; Li, Jingwen; Xu, Yin; Zhang, Anran; Shao, Shunzi; Yu, Xiaona; Yan, Wu; Xia, Yiju; Hu, Jiali; Fang, Dianchun

    2016-06-01

    Barrett's esophagus (BE) is essentially a metaplasia in which the normal stratified squamous epithelium is replaced by columnar epithelium. This study focuses on the involvement of OCT4 and SOX2, 2 key cell-reprogramming factors, in the deoxycholic acid (DCA)-induced expression of the intestinal hallmarks Cdx2 and MUC2 using both in vivo and in vitro models. Up-regulated expression of OCT4 and down-regulated expression of SOX2 were observed in BE compared with normal esophagus and esophagitis. Consistent with the data in vivo, DCA induced time-dependent expression of OCT4 at both the mRNA and protein levels and decreased nuclear expression of SOX2 in Het-1A cells. Down-regulation of OCT4 expression by siRNA abrogated DCA-induced expression of Cdx2 and MUC2, whereas siRNA against SOX2 significantly upregulated the expression of both Cdx2 and MUC2. Our data indicate that both OCT4 and SOX2 play important roles in the development of BE triggered by bile acid reflux. PMID:27096226

  3. Influence of reflux and central obesity on intercellular space diameter of esophageal squamous epithelium

    PubMed Central

    Blevins, Christopher H; Sharma, Anamay N; Johnson, Michele L; Geno, Deborah; Gupta, Milli; Bharucha, Adil E; Katzka, David A

    2015-01-01

    Background While central obesity increases gastroesophageal reflux (GER) by mechanically disrupting the anti-reflux barrier, limited data exist on pathways by which central obesity may potentiate esophageal injury by non-mechanical means. Obesity has been associated with an impaired epithelial intestinal barrier. Objective We aimed to assess the influence of central obesity and reflux on the squamous esophageal epithelial intercellular space diameter (ICSD). Methods The ICSD was measured using electron microscopy in esophageal biopsies from individuals who underwent ambulatory pH monitoring and endoscopy. Anthropometric measurements were obtained on all participants. Participants were classified into four groups: with and without central obesity and reflux. Results Sixteen individuals were studied with four in each study group. The mean ICSD was almost three-fold greater (p < 0.001) in the group with central obesity without reflux, compared to controls without central obesity and reflux. It was also comparable to the ICSD in groups with acid reflux only and those with both reflux and central obesity. Conclusions There is evidence of esophageal squamous ICSD increase in individuals with central obesity who do not have evidence of acid and nonacid reflux on ambulatory pH monitoring. This may reflect a mechanism by which central obesity potentiates reflux-induced esophageal injury and inflammation. PMID:27087944

  4. Infrared spectroscopic characteristics of normal and malignant colonic epithelium

    NASA Astrophysics Data System (ADS)

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

    1998-04-01

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

  5. Quantitative electron microscopic analysis of the epithelium of normal human alveolar mucosa.

    PubMed

    Bernimoulin, J P; Schroeder, H E

    1977-05-31

    The epithelium of normal human alveolar mucosa originating from the anterior vestibulum was subjected to stereologic analysis. Eight biopsies were collected half-way between the muco gingival junction and the vestibular fornix from 20 to 50 year-old females, and processed for light and electron microscopy. At two levels of magnification, electron micrographs were sampled from four artificially selected strata in regions of epithelial ridges. Stereologic point counting based on a computer-aided system for analyzing stratified epithelia served for examining a total of about 860 electron micrographs. The alveolar epithelium was 0.26 mm thick, occasionally interdigitated by short, slender connective tissue papillae, and consisted of (1) a narrow basal and suprabasal, and (2) a broad spinous and surface compartment. It displayed a differentiation pattern which, in most subjects studied, was similar to that of normal human buccal epithelium, however, on the average, produced less mature surface cells. This pattern was expressed mainly by a density increase of cytoplasmic filaments (98 A in diameter), a concomitant decrease of the cytoplasmic ground substance, the formation of dark-cored membrane coating granules, and invividually variable amounts of glycogen deposition. In some subjects, a mixed differentiation pattern was found. The structural organization of alveolar epithelium, in analogy to cheek epithelium, was compatible with the function of distensibility.

  6. Cavitary lung cancer lined with normal bronchial epithelium and cancer cells.

    PubMed

    Goto, Taichiro; Maeshima, Arafumi; Oyamada, Yoshitaka; Kato, Ryoichi

    2011-01-01

    Reports of cavitary lung cancer are not uncommon, and the cavity generally contains either dilated bronchi or cancer cells. Recently, we encountered a surgical case of cavitary lung cancer whose cavity tended to enlarge during long-term follow-up, and was found to be lined with normal bronchial epithelium and adenocarcinoma cells. PMID:21980325

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

    PubMed

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

    2015-03-01

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

  8. Esophagitis

    MedlinePlus

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

  9. 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

  10. Cyclooxygenase-2 expression in esophageal epithelium before and after photodynamic therapy for Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma.

    PubMed

    Yachimski, Patrick; Mino-Kenudson, Mari; Sherwood, Margaret E; Puricelli, William P; Nishioka, Norman S; Lauwers, Gregory Y

    2011-12-01

    Cyclooxygenase-2 expression is upregulated in Barrett's esophagus and esophageal adenocarcinoma. Photodynamic therapy using porfimer sodium can result in ablation of dysplasia and intramucosal carcinoma, eradication of Barrett's esophagus, and restitution of squamous epithelium. The aim of this study was to determine the effect of photodynamic therapy on cyclooxygenase-2 expression in esophageal epithelium. Paired pre- and post-photodynamic therapy biopsy samples from the same anatomical levels of 20 individuals who had undergone photodynamic therapy for Barrett's esophagus with high-grade dysplasia and/or intramucosal carcinoma were immunostained using a cyclooxygenase-2 monoclonal antibody. Cyclooxygenase-2 expression was graded in squamous epithelium, Barrett's esophagus, and neoplasia (if present) as follows: grade 0 (no staining), grade 1 (staining in 1-10% of cells), grade 2 (staining in 11-90% of cells), and grade 3 (staining in >90% of cells). Pre-photodynamic therapy median cyclooxygenase-2 expression was grade 2 (range 1-3) in neoplastic foci and grade 1 (range 1-3) in nondysplastic Barrett's esophagus (P=0.0009 for pairwise comparison). With the exception of a few cells staining in the basal epithelial layers, median cyclooxygenase-2 expression was graded as 0 (similar to controls) in both pre-photodynamic therapy squamous epithelium and post-photodynamic therapy neosquamous epithelium. This was significantly lower when compared to either neoplastic foci (P<0.0001) or nondysplastic Barrett's esophagus (P<0.0001) pre-photodynamic therapy. Notably, in four patients with post-photodynamic therapy recurrent neoplasia, cyclooxygenase-2 expression returned to elevated levels. Cyclooxygenase-2 expression is elevated in Barrett's esophagus with high-grade dysplasia or intramucosal carcinoma prior to photodynamic therapy. Following successful photodynamic therapy, cyclooxygenase-2 expression in neosquamous epithelium returns to a low baseline level similar to

  11. Caspase-3 expression in normal oral epithelium, oral submucous fibrosis and oral squamous cell carcinoma

    PubMed Central

    Veeravarmal, Veeran; Austin, Ravi David; Siddavaram, Nagini; Thiruneelakandan, Sambanthan; Nassar, Mohamed Hanifa Mohamed

    2016-01-01

    Context: The epithelium atrophy, as the oral submucous fibrosis (OSMF) progresses, is believed to be an after effect of stromal fibrosis, hyalinization, decrease in vascularity and cellularity and is considered as “ischemic atrophy.” Due to hypoxia, caspase-3 get activation and subsequent decrease in viable cell count can occur. Aims and Objectives: To determine caspase-3 expression in various grades of OSMF and oral squamous cell carcinoma (OSCC) to find out whether upregulation of apoptosis is responsible for the epithelial changes in OSMF. Subjects and Methods: The control tissue (15 samples from normal oral mucosa) and study group comprising 97 cases of OSMF of different grades and OSCC associated with OSMF were stained with caspase-3 antibody, and the percentage of positive cells was calculated using ImageJ software. Statistical Analysis: The results obtained were statistically analyzed using ANOVA and Tukey's honest significance difference test and Mann–Whitney U-test. Results: There was a nuclear expression of caspase-3 in basal and parabasal layers of normal epithelium. There was cytoplasmic expression of caspase-3 in OSMF without dysplasia, total absence of caspase-3 expression in dysplastic epithelium and in majority cases of OSCC. The caspase-3 percentage was increased in OSMF (0%–53%) when compared with OSCC (0%–8%). The statistical comparison of caspase-3 among normal, OSMF and OSCC patients revealed significant correlation (P < 0.00010). The comparison within different grades of OSMF and between dysplastic and nondysplastic epithelium OSMF also showed significance (P < 0.019). Conclusions: The decreased expression of caspase-3 in disease progression reflects its role in the malignant transformation. PMID:27721610

  12. 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

  13. The normal breast epithelium of women with breast cancer displays an aberrant response to estradiol.

    PubMed

    Khan, S A; Sachdeva, A; Naim, S; Meguid, M M; Marx, W; Simon, H; Halverson, J D; Numann, P J

    1999-10-01

    Breast epithelial response to estradiol may play an important role in breast cancer etiology. We have examined the relationship between serum estradiol and progesterone levels and normal breast epithelial expression of estrogen receptor (ER) alpha, progesterone receptor (PgR), and epithelial proliferation (as reflected by the Ki-67 labeling index) in 121 women (50 newly diagnosed breast cancer cases and 71 benign breast disease controls). Simultaneous samples of grossly normal breast tissue and venous blood were obtained from women undergoing breast surgery. Serum estradiol and progesterone levels were measured by radioimmunoassay; breast epithelial ER, PgR, and Ki-67 expression was measured by immunohistochemistry. Linear regression, controlled for patient age and ductal and lobular composition of the tissue, showed that the breast epithelium of control women displayed an inverse correlation between serum estradiol and ER-alpha, which was not seen in case women (P for the difference in regression slopes = 0.001). PgR expression displayed a significant positive correlation with serum estradiol in cases, but not in controls. Epithelial proliferation had no relationship to either estradiol or progesterone in both cases and controls but showed an inverse relationship with ER in controls and a direct relationship in cases (P for the difference in regression slopes = 0.066). These results suggest a dysregulation of hormonal response in the normal breast epithelium of high-risk women, with lack of regulation of ER by estradiol, increased estrogen responsiveness as reflected by PgR expression, and a dissociation of ER expression and proliferative response.

  14. 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.

  15. 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

  16. Effects of Lugol staining on stenosis formation induced by radiofrequency ablation of esophageal squamous epithelium: a study in a porcine model.

    PubMed

    Schölvinck, D W; Alvarez Herrero, L; Visser, M; Bergman, J J G H M; Weusten, B L A M

    2015-10-01

    Preliminary data show higher stricture rates after radiofrequency ablation (RFA) for early esophageal squamous neoplasia compared with Barrett's esophagus. We studied the effects of Lugol stain (LS) directly prior to RFA on stricture formation in squamous epithelium. Of 16 pigs, the distal half of the esophagus was LS, followed by circumferential RFA (single application 12 J/cm(2) ) in the unstained and stained esophagus. Pigs were euthanized at day 0 (n = 4), 3 (n = 4), or 28 (n = 8). Histology was evaluated in four areas: blank-control (no RFA, no LS), blank-RFA (no LS), LS+RFA, and LS-control (no RFA). Stenosis severity in LS+RFA and blank-RFA at 28 days was assessed by the ratio of the mucosal diameter at the RFA area to the diameter 2 cm proximal of this zone. Histology showed submucosal edema in 50% of LS+RFA versus 0% in blank-RFA. Severity and depth of inflammation (day 3) was equal in LS+RFA and blank-RFA. Severity and depth of fibrosis (day 28) appeared more severe in LS+RFA. Consequently, stenosis was present in 100% (LS+RFA) versus 12.5% (blank-RFA). The stenosis-severity ratio was 0.40 (interquartile range 0.29-0.45) in LS+RFA versus 0.73 (interquartile range 0.64-0.78) in blank-RFA (P = 0.012). Limitations of this study were the difference in uptake of LS between pigs and humans, the difference in esophageal anatomy between pigs and humans, and between the proximal and distal esophagus within pigs. In conclusion, in the porcine squamous esophagus, stenosis rate and severity after RFA increased when preceded by LS. LS may be contributing in the altered response of squamous epithelium to RFA as compared with Barrett's esophagus.

  17. 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.

  18. Tannic acid binding of cell surfaces in normal, premalignant, and malignant squamous epithelium of the human uterine cervix.

    PubMed

    Davina, J H; Lamers, G E; van Haelst, U J; Kenemans, P; Stadhouders, A M

    1984-01-01

    Alterations in tannic acid (TA) binding capacity of cell surface carbohydrates in normal, premalignant, and malignant squamous epithelium of the human uterine cervix have been studied using electron microscopic visualization in combination with microdensitometric evaluation. While in normal epithelium there is distinct binding in four to five cell layers of the deep intermediate zone, cells of carcinoma in situ and invasive cancer lesions lack TA binding. In moderate dysplasia an intermediate reacting pattern is found. Deep intermediate cells in areas bordering the carcinoma in situ lesions do not show any binding, although their ultrastructure cannot be distinguished from similar cells in normal tissue. The TA deposition within the deep intermediate zone is probably related to the presence here of glycoprotein-containing membrane-coating granules. The finding that TA binding discriminates between cells in normal squamous epithelium and morphologically normal cells in juxtaposition with lesional areas in premalignant and malignant epithelium opens the possibility for a more reliable cytologic diagnosis of cervical epithelial neoplasia.

  19. Metachronal activity of cultured mucociliary epithelium under normal and stimulated conditions.

    PubMed

    Gheber, L; Priel, Z

    1994-01-01

    In the present work we measured in real time the metachronism and degree of correlation between beating cilia from cultured mucociliary epithelium. The method is based on simultaneous measurement of ciliary beat frequency, phase shifts, and correlation factors in two directions: parallel and perpendicular to the effective stroke direction (ESD). From the phase shifts the lengths of wave components, and consequently the metachronal wavelength and direction, were evaluated. On active ciliary areas of cultured frog esophagus under normal conditions, a relatively high degree of correlation is observed, but cilia are more correlated in direction parallel to ESD which is also the direction of the mucus propulsion. The length of the wave component parallel to ESD is more than twice as large as that of the perpendicular component. The metachronal wavelength was found to be in the range of 5-9 microns, and the direction of the wave propagation was in the range of 90 degrees-125 degrees clockwise to the ESD. When ciliary beat frequency was rapidly increased by extracellular ATP or acetylcholine, only minor effects were observed on the degree of correlation between beating cilia. The length of the wave component parallel to ESD showed the most dramatic effect increasing up to tenfold. The perpendicular to ESD component was not affected by the stimulation. Consequently, the metachronism became more laeoplectic with the angle between the ESD and the wave directions decreasing by 10 degrees-30 degrees, and the metachronal wavelength remained unaltered.

  20. 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

  1. 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

  2. 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

  3. Quantitative analysis of squamous epithelium of normal palatal mucosa in guinea pigs.

    PubMed

    Andersen, L; Schroeder, H E

    1978-07-01

    The epithelium of intact guinea pig palate was subjected to stereologic analysis in a study of structural alterations in the keratinizing epithelium in response to wounding. Point counting procedures were employed to analyse electron micrographs sampled from three epithelial strata in biopsies collected from five animals. The differentiation pattern of the guinea pig palate epithelium displayed the following structural density gradients from basal to granular layers: descending gradients of metabolically active organelles, ascending gradient of bundled filaments coupled with the appearance of membrane coating granules and keratohyalin granules, and a plateau-like gradient of cytoplasmic ground substance. This pattern of epithelial differentiation is basically identical to that of human hard palate epithelium and epidermis. Regional and species variations in structure of keratinizing epithelia are suggested based on interepithelial differences in morphometric parameters.

  4. 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.

  5. 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

  6. 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.

  7. Ion transport across CF and normal murine olfactory and ciliated epithelium

    PubMed Central

    Grubb, B. R.; Rogers, T. D.; Boucher, R. C.; Ostrowski, L. E.

    2009-01-01

    The nasal epithelium of the cystic fibrosis (CF) mouse has been used extensively in CF research because it exhibits ion transport defects similar to those of human CF airways. This tissue is composed of ∼50% olfactory (OE) and ∼50% ciliated epithelium (CE), and on the basis of previous observations, we hypothesized that a significant fraction of the bioelectric signals from murine nasal tissue may arise from OE rather than CE, while CE is the target tissue for CF gene therapy. We compared the bioelectric properties of isolated OE from the nasal cavity and CE from the nasopharynx in Ussing chamber studies. Hyperabsorption of Na+ [amiloride response; CF vs. wild type (WT)] was ∼7.5-fold greater in the OE compared with the CE. The forskolin response in native tissues did not reliably distinguish genotypes, likely due to a cyclic nucleotide-gated cation conductance in OE and a calcium-mediated Cl− conductance in CE. By potential difference assay, hyperabsorption of Na+ (CF vs. WT) and the difference in response to apical 0 Cl− buffer (CF vs. WT) were ∼2-fold greater in the nasal cavity compared with the nasopharynx. Our studies demonstrate that in the CF mouse, both the hyperabsorption of Na+ and the Cl− transport defect are of larger magnitude in the OE than in the CE. Thus, while the murine CF nasal epithelium is a valuable model for CF studies, the bioelectrics are likely dominated by the signals from the OE, and assays of the nasopharynx may be more specific for studying the ciliated epithelium. PMID:19321738

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

    PubMed Central

    2014-01-01

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

  9. [Esophageal dysphagia].

    PubMed

    Thumshirn, M

    2007-04-01

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

  10. 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

  11. 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

  12. 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.

  13. 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

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

    PubMed

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

    2015-01-01

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

  15. 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

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

    PubMed

    Wang, Rui-Hua

    2015-05-01

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

  17. Proto-oncogenes and p53 protein expression in normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia.

    PubMed

    Ngan, H Y; Liu, S S; Yu, H; Liu, K L; Cheung, A N

    1999-10-01

    The aim of this study was to study the protein expression of six proto-oncogenes (epidermal growth factor receptor (EGFR), c-fms, c-myc, c-kit, c-erbB-2 and pan-ras) and one tumour suppressor gene (TP53), by immunohistochemical staining of normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia (CIN). Paraffin sections of 45 normal cervical specimens, 38 CIN grade one (CIN1), 37 CIN2 and 43 CIN3 were studied. An immunohistochemical (IHC) score was derived from the intensity of staining and the percentages of cells stained. In normal cervical specimens, a higher IHC score was found with EGFR and c-fms in superficial (S), intermediate (I) and parabasal (PB) cells compared with basal cells. In contrast, a higher IHC score was found with c-erbB-2 in basal cells in normal cervical specimens. Dysplastic cells in CIN had a higher IHC score with c-myc and c-erbB-2 than normal S/I and PB cells. Dysplastic cells had a higher score with EGFR than normal basal cells. However, a higher IHC score with EGFR and c-fms was found in normal S/I cells than dysplastic cells. These findings suggested that EGFR and c-fms were activated in more differentiated normal cells but were less active in less differentiated normal basal cells. However, EGFR was reactivated in dysplastic cells. Meanwhile, c-erbB-2 was activated in less differentiated normal basal cells and dysplastic cells, and was less active in differentiated normal cells. c-myc was activated in dysplastic cells. c-fms was more active in more differentiated normal cells and was not activated in less differentiated or dysplastic cells. c-kit, pan-ras and TP53 were not activated in normal nor dysplastic cervical cells. These results suggest EGFR, c-erbB-2 and c-myc may be important proto-oncogenes in CIN and that antibodies or anti-genes targeted against them may alter the progress of CIN to invasive cancer.

  18. Polaprezinc protects normal intestinal epithelium against exposure to ionizing radiation in mice

    PubMed Central

    Odawara, Soichi; Doi, Hiroshi; Shikata, Toshiyuki; Kitajima, Kazuhiro; Suzuki, Hitomi; Niwa, Yasue; Kosaka, Kengo; Tarutani, Kazuo; Tsujimura, Tohru; Kamikonya, Norihiko; Hirota, Shozo

    2016-01-01

    Polaprezinc (PZ), an antiulcer drug, has been reported to have antioxidant effects. The purpose of the present study was to assess the radioprotective effects of PZ in the normal intestine of C57BL/6J mice. PZ was orally administered at 100 mg/kg body weight in the drinking water. Firstly, the present study compared the survival of normal intestinal crypt epithelial cells with mice that received PZ prior to or following irradiation. Next, the present study examined the sequential changes of the incidence of apoptosis in the normal intestine of mice that received irradiation. The mice that received PZ prior to irradiation demonstrated a stronger protective effect on the normal intestine compared with those that received PZ after irradiation. The present study therefore administrated PZ 2 h before irradiation in the subsequent experiments. The mice receiving PZ developed fewer apoptotic cells in the duodenum, jejunum and ileum. Radiation-induced cell death occurred with a peak at position 10 or lower from the base of the crypt axis, and was subsequently reduced by PZ treatment. Pretreatment with PZ protected the normal intestinal tissues from radiation-induced apoptosis.

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

    PubMed

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

    2010-01-01

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

  20. Transcriptional regulation by normal epithelium of premalignant to malignant progression in Barrett’s esophagus

    PubMed Central

    Zeng, Jia; Kelbauskas, Laimonas; Rezaie, Aida; Lee, Kristen; Ueberroth, Benjamin; Gao, Weimin; Derkach, Dmitry; Tran, Thai; Smith, Dean; Bussey, Kimberly J.; Meldrum, Deirdre R.

    2016-01-01

    In carcinogenesis, intercellular interactions within and between cell types are critical but remain poorly understood. We present a study on intercellular interactions between normal and premalignant epithelial cells and their functional relevance in the context of premalignant to malignant progression in Barrett’s esophagus. Using whole transcriptome profiling we found that in the presence of normal epithelial cells, dysplastic cells but not normal cells, exhibit marked down-regulation of a number of key signaling pathways, including the transforming growth factor beta (TGFβ) and epithelial growth factor (EGF). Functional assays revealed both cell types showed repressed proliferation and significant changes in motility (speed, displacement and directionality) as a result of interactions between the two cell types. Cellular interactions appear to be mediated through both direct cell-cell contact and secreted ligands. The findings of this study are important in that they reveal, for the first time, the effects of cellular communication on gene expression and cellular function between premalignant (dysplastic) epithelial cells and their normal counterparts. PMID:27731371

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

    PubMed

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

    2014-11-01

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

  2. TWIST and p-Akt immunoexpression in normal oral epithelium oral dysplasia and in oral squamous cell carcinoma

    PubMed Central

    Yamamoto, Fernanda-Paula; Corrêa Pontes, Flávia-Sirotheau; Cury, Sérgio-Elias; Fonseca, Felipe-Paiva; Rebelo-Pontes, Hélder; Pinto-Júnior, Décio-dos Santos

    2012-01-01

    Objectives: The aim of this study was to evaluate the immunoexpression of TWIST and p-Akt proteins in oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC), correlating their expressions with the histological features of the lesions. Study design: Immunohistochemical studies were carried out on 10 normal oral epithelium, 30 OL and 20 OSCC formalin-fixed, paraffin-embedded tissue samples. Immunoperoxidase reactions for TWIST and p-Akt proteins were applied on the specimens and the positivity of the reactions was calculated for 1000 epithelial cells. Results: Kruskal-Wallis and Dunn’s post tests revealed a significant difference in TWIST and p-Akt immunoexpression among normal oral mucosa, OL and OSCC. In addition, a significant positive correlation was found between TWIST and p-Akt expressions according to the Pearson’s correlation test. Conclusions: The results obtained in the current study suggest that TWIST and p-Akt may participate of the multi-step process of oral carcinogenesis since its early stages. Key words: Oral cancer, oral leukoplakia, dysplasia, immunohistochemistry. PMID:21743395

  3. 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

  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. 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

  6. 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.

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

    PubMed

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

    2015-11-01

    The ly-6 proteins are a large family of proteins that resemble the snake three finger alpha toxins such as 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

  8. 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

  9. Zinc-rich inhibitor of apoptosis proteins (IAPs) as regulatory factors in the epithelium of normal and inflamed airways.

    PubMed

    Roscioli, Eugene; Hamon, Rhys; Lester, Susan; Murgia, Chiara; Grant, Janet; Zalewski, Peter

    2013-04-01

    Integrity of the airway epithelium (AE) is important in the context of inhaled allergens and noxious substances, particularly during asthma-related airway inflammation where there is increased vulnerability of the AE to cell death. Apoptosis involves a number of signaling pathways which activate procaspases leading to cleavage of critical substrates. Understanding the factors which regulate AE caspases is important for development of strategies to minimize AE damage and airway inflammation, and therefore to better control asthma. One such factor is the essential dietary metal zinc. Zinc deficiency results in enhanced AE apoptosis, and worsened airway inflammation. This has implications for asthma, where abnormalities in zinc homeostasis have been observed. Zinc is thought to suppress the steps involved in caspase-3 activation. One target of zinc is the family of inhibitor of apoptosis proteins (IAPs) which are endogenous regulators of caspases. More studies are needed to identify the roles of IAPs in regulating apoptosis in normal and inflamed airways and to study their interaction with labile zinc ions. This new information will provide a framework for future clinical studies aimed at monitoring and management of airway zinc levels as well as minimising airway damage and inflammation in asthma.

  10. The interaction of epithelial Ihha and mesenchymal Fgf10 in zebrafish esophageal and swimbladder development.

    PubMed

    Korzh, Svitlana; Winata, Cecilia Lanni; Zheng, Weiling; Yang, Shulan; Yin, Ao; Ingham, Phillip; Korzh, Vladimir; Gong, Zhiyuan

    2011-11-15

    Developmental patterning and growth of the vertebrate digestive and respiratory tracts requires interactions between the epithelial endoderm and adjacent mesoderm. The esophagus is a specialized structure that connects the digestive and respiratory systems and its normal development is critical for both. Shh signaling from the epithelium regulates related aspects of mammalian and zebrafish digestive organ development and has a prominent effect on esophageal morphogenesis. The mechanisms underlying esophageal malformations, however, are poorly understood. Here, we show that zebrafish Ihha signaling from the epithelium acting in parallel, but independently of Shh, controls epithelial and mesenchymal cell proliferation and differentiation of smooth muscles and neurons in the gut and swimbladder. In zebrafish ihha mutants, the esophageal and swimbladder epithelium is dysmorphic, and expression of fgf10 in adjacent mesenchymal cells is affected. Analysis of the development of the esophagus and swimbladder in fgf10 mutant daedalus (dae) and compound dae/ihha mutants shows that the Ihha-Fgf10 regulatory interaction is realized through a signaling feedback loop between the Ihha-expressing epithelium and Fgf10-expressing mesenchyme. Disruption of this loop further affects the esophageal and swimbladder epithelium in ihha mutants, and Ihha acts in parallel to but independently of Shha in this process. These findings contribute to the understanding of epithelial-mesenchymal interactions and highlight an interaction between Hh and Fgf signaling pathways during esophagus and swimbladder development. PMID:21925490

  11. 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

  12. 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

  13. 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

  14. 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.

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

    NASA Astrophysics Data System (ADS)

    Overholt, Bergein F.; Panjehpour, Masoud

    1995-03-01

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

  16. Expression of the carcinoma markers: the sialylated Lewis A and X carbohydrate antigens in normal laryngeal surface epithelium and submucosal glands from old humans.

    PubMed

    Kirkeby, Svend; Moe, Dennis

    2013-03-01

    Aberrant surface expression of the carbohydrate ABH and Lewis antigens are often used as markers for the diagnosis of cancer, but while the distribution of these histo-blood group antigens is relatively well-described in tissues and organs from young and middle-aged humans little is known of their expression in old age. The objective for this study was to estimate if the Lewis A and X antigens together with their sialylated modifications, are expressed in sections of normal laryngeal tissue from old humans. Antibodies directed against the tumor markers Sialyl Lewis A and Sialyl Lewis X showed positive reaction in the surface epithelia from normal larynx autopsies obtained from people aged 77-90 years. The sialylated and non-sialylated Lewis A antigens were more frequently expressed in the pseudostratified epithelium than in squamous surface epithelium. Both the sialylated and the non-sialylated carbohydrates were stained in the submucosal glands in all the autopsies. In conclusion, visualization of Lewis tumor markers in the larynx should be interpreted with great care, as they may be present in normal laryngeal epithelial cells from old humans.

  17. Ingestion of a carbonated beverage decreases lower esophageal sphincter pressure and increases frequency of transient lower esophageal sphincter relaxation in normal subjects.

    PubMed

    Shukla, Akash; Meshram, Megha; Gopan, Amrit; Ganjewar, Vaibhav; Kumar, Praveen; Bhatia, Shobna J

    2012-06-01

    Transient lower esophageal sphincter relaxation (tLESR) and decreased basal lower esophageal sphincter (LES) pressure are postulated mechanisms of gastroesophageal reflux (GER). There is conflicting evidence on the effect of carbonated drinks on lower esophageal sphincter function. This study was conducted to assess the effect of a carbonated beverage on tLESR and LES pressure. High resolution manometry tracings (16 channel water-perfused, Trace 1.2, Hebbard, Australia) were obtained in 18 healthy volunteers (6 men) for 30 min each at baseline, and after 200 mL of chilled potable water and 200 mL of chilled carbonated cola drink (Pepsi [Pepsico India Ltd]). The sequence of administration of the drinks was determined by random number method generated by a computer. The analysis of tracings was done using TRACE 1.2 software by a physician who was unaware of the sequence of administration of fluids. The mean (SD) age of the participant was 37.3 (12.9) years. The median (range) frequency of tLESr was higher after the carbonated beverage (10.5 [0-26]) as compared to baseline (0 [0-3], p = 0.005) as well as after water (1 [0-14], p = 0.010). The LES pressure decreased after ingestion of the carbonated beverage (18.5 [11-37] mmHg) compared to baseline (40.5 [25-66] mmHg, p = 0.0001) and after water (34 [15-67] mmHg, p = 0.003). Gastric pressure was not different in the three groups. Ingestion of a carbonated beverage increases tLESr and lowers LES pressure in healthy subjects.

  18. Ingestion of a carbonated beverage decreases lower esophageal sphincter pressure and increases frequency of transient lower esophageal sphincter relaxation in normal subjects.

    PubMed

    Shukla, Akash; Meshram, Megha; Gopan, Amrit; Ganjewar, Vaibhav; Kumar, Praveen; Bhatia, Shobna J

    2012-06-01

    Transient lower esophageal sphincter relaxation (tLESR) and decreased basal lower esophageal sphincter (LES) pressure are postulated mechanisms of gastroesophageal reflux (GER). There is conflicting evidence on the effect of carbonated drinks on lower esophageal sphincter function. This study was conducted to assess the effect of a carbonated beverage on tLESR and LES pressure. High resolution manometry tracings (16 channel water-perfused, Trace 1.2, Hebbard, Australia) were obtained in 18 healthy volunteers (6 men) for 30 min each at baseline, and after 200 mL of chilled potable water and 200 mL of chilled carbonated cola drink (Pepsi [Pepsico India Ltd]). The sequence of administration of the drinks was determined by random number method generated by a computer. The analysis of tracings was done using TRACE 1.2 software by a physician who was unaware of the sequence of administration of fluids. The mean (SD) age of the participant was 37.3 (12.9) years. The median (range) frequency of tLESr was higher after the carbonated beverage (10.5 [0-26]) as compared to baseline (0 [0-3], p = 0.005) as well as after water (1 [0-14], p = 0.010). The LES pressure decreased after ingestion of the carbonated beverage (18.5 [11-37] mmHg) compared to baseline (40.5 [25-66] mmHg, p = 0.0001) and after water (34 [15-67] mmHg, p = 0.003). Gastric pressure was not different in the three groups. Ingestion of a carbonated beverage increases tLESr and lowers LES pressure in healthy subjects. PMID:22791463

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

    The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division and motility, and the epithelial-mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barrett's Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope to study the mechanical properties of single adherent cells. Sixty four force indentation curves were taken over the nucleus of each cell in an 8 × 8 grid pattern. Analyzing the force indentation curves, indentation depth-dependent Young's moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Young's moduli were calculated to 4.7 kPa for EPC2 (n = 18 cells), 3.1 kPa for CP-A (n = 10) and 2.6 kPa for CP-D (n = 19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n = 5), significant stiffening was found (9.9 kPa), while CP-A cells (n = 5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n = 16). Some force-indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these 'breakthrough events' to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to 'crumble and yield' rather than their ability to 'bend and flex'.

  20. Eosinophilic gastroenteritis with esophageal involvement.

    PubMed

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

    1977-06-01

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

  1. Upper esophageal web due to a ring formed by a squamocolumnar junction with ectopic gastric mucosa (another explanation of the Paterson-Kelly, Plummer-Vinson syndrome).

    PubMed

    Weaver, G A

    1979-12-01

    A patient is presented with Barrett's esophagus (lower esophagus lined with columnar epithelium) who also has a band of columnar epithelium in the upper esophagus separated from that below by normal squamous epithelium in the midesophagus. The upper most squamocolumnar junction coincided with or formed a mucosal ring as seen at endoscopy. This ring, which was first seen on barium swallow, has the radiographic appearance of that associated with the Paterson-Kelly syndrome. This patient's unique findings may provide further insight into the etiology of upper esophageal webs or rings (Paterson-Kelly syndrome).

  2. Different production of interleukin-1alpha, interleukin-1beta and interleukin-8 from cholesteatomatous and normal epithelium.

    PubMed

    Chung, J W; Yoon, T H

    1998-06-01

    Cholesteatomatous bone destruction is caused by an increase in collagenase activity and activation of the osteoclasts. Cytokines. such as interleukins (IL), are important in intercellular communication in the mechanism of bone destruction. Middle ear cholesteatomas and external auditory canal skins (EACS) can be surgically obtained and cultured. The quantities of IL-1alpha, IL-1beta and IL-8 secretions were measured in the supernatant of each culture series. On the 2nd day of culture, the level of IL-1alpha was 0.60+/-0.13 (pg/microg of total protein) in cholesteatoma, and 0.25+/-0.02 in EACS. The levels of IL-1beta in cholesteatoma and EACS were 0.41+/-0.06 and 0.24+/-0.02, respectively. The levels of IL-8 in cholesteatoma and EACS were 146.50+/-32.37 and 50.40+/-6.24, respectively. After 2 days, the levels of IL-1alpha and IL-8 of each tissue decreased. The value from fibroblasts did not show a significant difference between cholesteatoma and EACS, and the values did not change as time passed. We can conclude that the IL-1alpha and IL-8 from the cholesteatomatous epithelium are responsible for the cholesteatomatous bone destruction and certain substances from the subepithelial granulation tissue can stimulate the cholesteatoma to produce IL-1alpha and IL-8.

  3. 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

  4. Growth hormone is secreted by normal breast epithelium upon progesterone stimulation and increases proliferation of stem/progenitor cells.

    PubMed

    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

    2014-06-01

    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.

  5. 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

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

    SciTech Connect

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

    2011-12-01

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

  7. Defective Barrier Function in Neosquamous Epithelium

    PubMed Central

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

    2013-01-01

    BACKGROUND Radiofrequency ablation (RFA) of 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

  8. 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.

  9. 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

  10. 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

  11. 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 ...

  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

    ... 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 ...

  14. 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

  15. 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.

  16. Early transformative changes in normal ovarian surface epithelium induced by oxidative stress require Akt upregulation, DNA damage and epithelial-stromal interaction.

    PubMed

    King, Shelby M; Quartuccio, Suzanne M; Vanderhyden, Barbara C; Burdette, Joanna E

    2013-05-01

    Ovarian cancer is the deadliest gynecological malignancy due to detection of cancer at a late stage when the disease has metastasized. One likely progenitor cell type of ovarian cancer is the ovarian surface epithelium (OSE), which proliferates rapidly in the presence of inflammatory cytokines and oxidative stress following ovulation. To determine whether oxidative stress induces DNA damage leading to spontaneous transformative changes in normal OSE, an immortalized mouse OSE cell line (MOSE cells) or normal mouse ovarian organoids were treated with hydrogen peroxide (H2O2) and loss of contact inhibition was assessed by soft agar assay. In response to H2O2, OSE cells grown in 3D exhibited growth in soft agar but MOSE cells grown on 2D plastic did not, indicating a critical role for epithelial-stromal interactions in neoplastic initiation. Loss of contact inhibition in response to H2O2 correlated with an increase in proliferation, DNA damage and upregulation of the oncogene Akt1. Use of a reactive oxygen species scavenger or Akt inhibitor blocked H2O2-induced proliferation and growth in soft agar. Although parental MOSE cells did not undergo transformation by H2O2, MOSE cells stably overexpressing constitutively active myristoylated Akt or knockdown of phosphatase and tensin homolog (PTEN) exhibited loss of contact inhibition and increased proliferation. This study indicates that normal OSE undergo transformative changes induced by oxidative stress and that this process requires Akt upregulation and activation. A 3D model that retains tissue architecture is critical for studying this process and may lead to development of new intervention strategies directed at early stages of ovarian cancer.

  17. 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]).

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

    PubMed Central

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

    2015-01-01

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

  19. Four carcinoembryonic antigen subfamily members, CEA, NCA, BGP and CGM2, selectively expressed in the normal human colonic epithelium, are integral components of the fuzzy coat.

    PubMed

    Frängsmyr, L; Baranov, V; Hammarström, S

    1999-01-01

    To elucidate which of the seven transcriptionally active genes of the carcinoembryonic antigen (CEA) subfamily are expressed in human colon, we first examined mRNA expression using reverse transcriptase PCR. The result showed the CEA, nonspecific crossreacting antigen 50/90 (NCA), biliary glycoprotein (BGP), and carcinoembryonic antigen gene family member 2 (CGM2) mRNAs were expressed in the colon. To determine the cellular sources of these members within normal colonic mucosa, in situ hybridization and immunocytochemistry were then performed. CEA and NCA mRNAs were clearly detectable in the cytoplasm of columnar and goblet cells at the free luminal surface and the upper crypts with low hybridization in the mid crypt and the crypt base. In contrast, BGP and CGM2 mRNAs were restricted only to columnar cells at the upper third of the crypts and the luminal surface. Colon epithelium expression of CEA, NCA, BGP and CGM2 coincided with that of corresponding mRNAs. Ultrastructurally, CEA, NCA, BGP and CGM2 were localized mainly to the apical surface glycocalyx, the fuzzy coat, of columnar cells. Interestingly, these molecules were localized in different microdomains within the fuzzy coat. Furthermore, BGP was highly expressed in the fuzzy coat of cryptal caveolated cells. As integral components of the fuzzy coat, CEA, NCA, BGP and CGM2 can hardly function as intercellular adhesion molecules; they possibly play an important role in epithelial-microbial interactions.

  20. 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

  1. 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

  2. COX-2 mRNA expression in esophageal squamous cell carcinoma (ESCC) and effect by NSAID.

    PubMed

    Liu, X; Li, P; Zhang, S-T; You, H; Jia, J-D; Yu, Z-L

    2008-01-01

    To investigate cyclooxygenase-2 (COX-2) mRNA expression in human esophageal squamous cell carcinoma and the effect of a non-steroidal anti-inflammatory drug (NSAID) on it, in order to explore the mechanism of COX-2 in esophageal squamous cell carcinoma (ESCC) carcinogenesis and the ability of NSAID to prevent or treat ESCC. Frozen specimens of human ESCC and adjacent normal esophageal squamous epithelium pairs (n = 22) were examined for COX-2 mRNA expression by reverse-transcription polymerase chain reaction (RT-PCR). After incubation with aspirin (a non-selective COX inhibitor) or Nimesulide (a selective COX-2 inhibitor), the proliferation status of two human esophageal squamous cancer cell lines, EC-9706 and EC-109, was quantified by 3-(4,5-dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide assay. The expression of COX-2 mRNA in these cells was detected by RT-PCR. COX-2 mRNA was expressed in 12 of 22 (54.5%) ESCC tissue samples, but it was undetectable in all the specimens of adjacent normal esophageal squamous epithelium COX-2 mRNA expression. Both aspirin (5-20 mmol/L) and Nimesulide (0.1-0.8 mmol/L) inhibited EC-9706 cell line proliferation and suppressed its COX-2 mRNA expression dose-dependently. However, only aspirin (5-20 mmol/L) could inhibit proliferation in the EC-109 cell line and suppress COX-2 mRNA expression. Nimesulide (0.1-0.8 mmol/L) could neither inhibit EC-109 cell growth nor suppress COX-2 mRNA expression. COX-2 mRNA expression is a frequent phenomenon in human ESCC tissue samples and plays an important role in the carcinogenesis of ESCC. NSAID may be useful in the chemoprevention and therapy of human ESCC and its effects are likely to be mediated by modulating COX-2 activity.

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

    PubMed

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

    2013-01-01

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

  4. Esophagitis - infectious

    MedlinePlus

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

  5. Esophageal 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

  6. [Esophageal motility disorders].

    PubMed

    Dughera, L; Battaglia, E; Emanuelli, G

    2001-09-01

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

  7. 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

  8. 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 ...

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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

  14. Esophageal anastomosis.

    PubMed

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

    2015-01-01

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

  15. 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

  16. 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

  17. Pill esophagitis.

    PubMed

    Kikendall, J W

    1999-06-01

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

  18. 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

  19. 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

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

    PubMed

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

    2015-11-01

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

  1. 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

  2. Liquid-containing Refluxes and Acid Refluxes May Be Less Frequent in the Japanese Population Than in Other Populations: Normal Values of 24-hour Esophageal Impedance and pH Monitoring

    PubMed Central

    Kawamura, Osamu; Kohata, Yukie; Kawami, Noriyuki; Iida, Hiroshi; Kawada, Akiyo; Hosaka, Hiroko; Shimoyama, Yasuyuki; Kuribayashi, Shiko; Fujiwara, Yasuhiro; Iwakiri, Katsuhiko; Inamori, Masahiko; Kusano, Motoyasu; Hongo, Micho

    2016-01-01

    Background/Aims Twenty-four-hour esophageal impedance and pH monitoring allows detection of all types of reflux episodes and is considered the best technique for identifying gastroesophageal refluxes. However, normative data for the Japanese population are lacking. This multicenter study aimed to establish the normal range of 24-hour esophageal impedance and pH data both in the distal and the proximal esophagus in Japanese subjects. Methods Forty-two healthy volunteers (25 men and 17 women) with a mean ± standard deviation age of 33.3 ± 12.4 years (range: 22–72 years) underwent a combined 24-hour esophageal impedance and pH monitoring. According to the physical and pH properties, distal or proximal esophageal reflux events were categorized. Results Median 45 reflux events occurred in 24 hours, and the 95th percentile was 85 events. Unlike previous reports, liquid-containing reflux events are median 25/24 hours with the 95th percentile of 62/24 hours. Acidic reflux events were median 11/24 hours with the 95th percentile of 39/24 hours. Non-acidic gas reflux events were median 15/24 hours with the 95th percentile of 39/24 hours. Proximal reflux events accounted for 80% of the total reflux events and were mainly non-acidic gas refluxes. About 19% of liquid and mixed refluxes reached the proximal esophagus. Conclusions Unlike previous studies, liquid-containing and acidic reflux events may be less frequent in the Japanese population. Non-acidic gas reflux events may be frequent and a cause of frequent proximal reflux events. This study provides important normative data for 24-hour impedance and pH monitoring in both the distal and the proximal esophagus in the Japanese population. PMID:27247103

  3. NFkB and Nrf2 in esophageal epithelial barrier function

    PubMed Central

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

    2013-01-01

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

  4. Normalization.

    ERIC Educational Resources Information Center

    Cuevas, Eduardo J.

    1997-01-01

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

  5. 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

  6. A Rare Disease of the Digestive Tract: Esophageal Melanosis

    PubMed Central

    Destek, Sebahattin; Gul, Vahit Onur; Ahioglu, Serkan; Erbil, Yesim

    2016-01-01

    Esophageal melanosis which is characterized by melanocytic proliferation in the squamous epithelium of the esophagus and melanin accumulatin of esophageal mucosa (EM) is a rare disease of the digestive system. Although esophageal melanosis is considered to be a benign disease, its etiology is not cleared and has been reported to be the precursor lesion of esophageal primary melanomas. In this report, we aimed to note esophageal melanosis in a 55-year-old female case who applied to our clinic with difficulty in swallowing, burning behind the breastbone in the stomach, heartburn, indigestion, and pain in the upper abdomen after endoscopic and pathologic evaluation. Complaints dropped with anti-acid therapy and case was followed by intermittent endoscopic procedures because of precursor melanocytic lesions. PMID:27785326

  7. A randomized double-blind intervention study on the effect of calcium supplementation on esophageal precancerous lesions in a high-risk population in China.

    PubMed

    Wang, L D; Qiu, S L; Yang, G R; Lipkin, M; Newmark, H L; Yang, C S

    1993-01-01

    To determine whether dietary calcium supplementation affects esophageal precancerous lesions, 200 subjects with esophageal lesions in a high-risk area for esophageal cancer in China (Huixian, Henan) were randomly divided into 2 groups (100 subjects/group). Subjects in one group received an oral supplementation of calcium carbonate tablets (1200 mg of calcium daily), and subjects in the other group received placebo pills for 11 months. At the entry and the end of the trial, esophagoscopy was performed, and 2 or 3 biopsy specimens were taken from the middle and lower thirds of the esophagus and from macroscopic lesions, if any, of each subject for histopathology and cell proliferation analysis with deoxythymidine labeling. In comparison to normal epithelium, increased proliferative compartment size was observed in epithelia with hyperplasia or dysplasia. After the intervention, the percentage of individuals with "normal epithelium," "basal cell hyperplasia," "basal cell hyperplasia II," and "basal cell hyperplasia III and dysplasia" were 44, 31, 13, and 11% in the calcium group and 35, 39, 17, and 6% in the placebo group, respectively. The labeling index was 0.046 in the calcium group and 0.044 in the placebo group. After the intervention, the labeling index in basal cell layers 1 to 5, the major zone of cell proliferation, fell 38% in the calcium group and 44% in the placebo group from before the intervention. Therefore, in this study, calcium supplementation was not shown to have beneficial effects in alleviating precancerous lesions and abnormal cell proliferation patterns.

  8. Cell lineage-specific and differentiation-dependent patterns of CCAAT/enhancer binding protein alpha expression in the gut epithelium of normal and transgenic mice.

    PubMed Central

    Chandrasekaran, C; Gordon, J I

    1993-01-01

    The proliferation and differentiation programs of gut epithelial cells are expressed rapidly and perpetually along an anatomically well defined pathway. The mouse intestine thus provides an excellent in vivo model system to define the contributions of CCAAT enhancer binding protein alpha (C/EBP alpha) and related bZIP proteins to these processes. Immunocytochemical studies revealed that C/EBP alpha is produced in villus-associated enterocytes located in the duodenum and jejunum of adult mice. The protein is located in the cytoplasmic and nuclear compartments of these cells. C/EBP alpha is not detectable in proliferating and nonproliferating epithelial cells situated in small intestinal crypts nor is it evident in any gut epithelial cell lineage located in the ileum and colon. The related C/EBP beta and C/EBP delta proteins are not detectable by sensitive immunocytochemical methods in epithelial cells distributed along the duodenal-to-colonic axis. Developmental surveys indicate that C/EBP alpha is confined to postmitotic, villus-associated epithelial cells during conversion of the polyclonal intervillus epithelium to monoclonal crypts. Analyses of intestinal isografts reveal that these developmental stage-specific, lineage-specific, differentiation-dependent, and regional patterns of C/EBP alpha expression can be established and maintained in the absence of exposure to luminal contents. Transgenic mice containing nucleotides -1178 to +28 of the rat intestinal fatty acid binding protein gene (I-FABP-1178 to +28) linked to the simian virus 40 large tumor antigen (T antigen) gene express T antigen in villus-associated enterocytes. This results in reentry of enterocytes into the cell cycle and a silencing of C/EBP alpha expression without an apparent effect on the accumulation of several markers of this lineage's terminal differentiation program or on gut morphogenesis. These findings indicate that there is a relationship between expression of C/EBP alpha in

  9. Genome-wide profiling of the human papillomavirus DNA integration in cervical intraepithelial neoplasia and normal cervical epithelium by HPV capture technology

    PubMed Central

    Liu, Ying; Zhang, Chaoting; Gao, Weijiao; Wang, Limin; Pan, Yaqi; Gao, Yunong; Lu, Zheming; Ke, Yang

    2016-01-01

    HPV integration plays an important role in cervical carcinogenesis. HPV genotypes and the exact integration sites were investigated using HPV capture technology combined with next generation sequencing in 166 women. Three, one and six integration sites were verified in 7 HPV-positive ‘normal cervical epithelium’, 6 HPV-positive CIN2 and 15 HPV-positive CIN 3 samples, respectively. Of the 10 integrations, one and nine were involved with HPV33 and HPV16, respectively. Our study accurately evaluated HPV integration level in CINs and normal cervical tissues using high-throughput viral integration detection method providing basic evidence for HPV integration-driven cervical carcinogenesis. PMID:27759101

  10. Expression of transient receptor potential channel vanilloid (TRPV) 1–4, melastin (TRPM) 5 and 8, and ankyrin (TRPA1) in the normal and methimazole-treated mouse olfactory epithelium

    PubMed Central

    Nakashimo, Yousuke; Takumida, Masaya; Fukuiri, Takashi; Anniko, Matti; Hirakawa, Katsuhiro

    2010-01-01

    Conclusion: It is suggested that TRPV1, 2, 3, and 4, TRPM5 and 8, and TRPA1 may play several roles in the olfactory epithelium (OE), contributing to olfactory chemosensation, olfactory adaptation, olfactory-trigeminal interaction, and OE fluid homeostasis. In patients with olfactory disturbance, TRPV1 and TRPM8 may be closely related to a high rate of recognition of curry and menthol odors, while TRPV2 may also play a crucial role in the regeneration of olfactory receptor neurons. Objective: Expression of TRPV1–4, TRPM5 and 8, and TRPA1 in the normal and methimazole-treated mouse OE was analyzed. Methods: The localization of TRPV1–4, TRPM5 and 8, and TRPA1 in the OE of normal and methimazole-treated CBA/J mice was investigated by immunohistochemistry. Results: Normal OE showed a positive immunofluorescent reaction to TRPV1–4, TRPM5 and 8, and TRPA1. In lamina propria, the nerve fibers displayed TRPV 1, 2, and 3, TRPM8 and TRPA1. In the pathological condition, the expression of TRPV3, TRPV4, TRPM5, and TRPA1 was markedly reduced and took a long time to recover. In contrast, expression of TRPM8 was scarcely affected, even in the pathological condition, while TRPV1 and TRPV2 showed early recovery following methimazole treatment. PMID:20586674

  11. [Endoscopic surgery for benign esophageal diseases].

    PubMed

    Ozawa, Soji

    2006-07-01

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

  12. Nuclear receptor co-repressor is required to maintain proliferation of normal intestinal epithelial cells in culture and down-modulates the expression of pigment epithelium-derived factor.

    PubMed

    Doyon, Geneviève; St-Jean, Stéphanie; Darsigny, Mathieu; Asselin, Claude; Boudreau, Francois

    2009-09-11

    Stem cells of the gut epithelium constantly produce precursors that progressively undergo a succession of molecular changes resulting in growth arrest and commitment to a specific differentiation program. Few transcriptional repressors have been identified that maintain the normal intestinal epithelial cell (IEC) proliferation state. Herein, we show that the nuclear receptor co-repressor (NCoR1) is differentially expressed during the proliferation-to-differentiation IEC transition. Silencing of NCoR1 expression in proliferating cells of crypt origin resulted in a rapid growth arrest without associated cell death. A genechip profiling analysis identified several candidate genes to be up-regulated in NCoR1-deficient IEC. Pigment epithelium-derived factor (PEDF, also known as serpinf1), a suspected tumor suppressor gene that plays a key role in the inhibition of epithelial tissue growth, was significantly up-regulated in these cells. Chromatin immunoprecipitation experiments showed that the PEDF gene promoter was occupied by NCoR1 in proliferating epithelial cells. Multiple retinoid X receptor (RXR) heterodimers interacting sites of the PEDF promoter were confirmed to interact with RXR and retinoid acid receptor (RAR). Cotransfection assays showed that RXR and RAR were able to transactivate the PEDF promoter and that NCoR1 was repressing this effect. Finally, forced expression of PEDF in IEC resulted in a slower rate of proliferation. These observations suggest that NCoR1 expression is required to maintain IEC in a proliferative state and identify PEDF as a novel transcriptional target for NCoR1 repressive action.

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

    PubMed

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

    2008-04-15

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

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

    PubMed

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

    2015-12-14

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

  15. 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)

  16. 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

  17. 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

  18. Esophageal dilation in eosinophilic esophagitis.

    PubMed

    Richter, Joel E

    2015-10-01

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

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

    PubMed Central

    Yang, Liying; Francois, Fritz; Pei, Zhiheng

    2013-01-01

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

  20. Microscopic esophagitis and Barrett's esophagus: the histology report.

    PubMed

    Fiocca, Roberto; Mastracci, Luca; Milione, Massimo; Parente, Paola; Savarino, Vincenzo

    2011-03-01

    Gastro-esophageal reflux disease (GERD) is the most common digestive disease in industrialized countries (Europe and North America) and is associated with microscopic changes in the squamous epithelium. However, biopsy is not presently included in the routine diagnostic flow chart of GERD. In contrast, esophageal biopsy is mandatory when diagnosing Barrett's esophagus. High quality histology reports are necessary to provide information on diagnosis and can also be important for research and epidemiological studies. It has been evident for decades that pathology reports vary between institutions and even within a single institution. Standardization of reporting is the best way to ensure that information necessary for patient management is included in pathology reports. This paper details the histological criteria for diagnosing GERD-associated microscopic esophagitis, other forms of esophagitis with specific features and columnar metaplasia in the lower esophagus (Barrett's esophagus). It provides a detailed description of appropriate sampling criteria, individual lesions and how they contribute to the histology report.

  1. 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

  2. Desloratadine Induced Pill Esophagitis

    PubMed Central

    Alkim, Huseyin; Iscan, Mustafa

    2012-01-01

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

  3. 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.

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

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. 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

  7. 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

  8. Current Management of Eosinophilic Esophagitis 2015.

    PubMed

    Richter, Joel E

    2016-02-01

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

  9. 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

  10. 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…

  11. [Autocrine growth mechanisms of cholesteatoma epithelium].

    PubMed

    Schilling, V; Holly, A; Bujía, J; Schulz, P

    1993-07-01

    Transforming growth factor alpha (TGF alpha) and interleukin 1 alpha (IL-1 alpha) are known to be produced by normal human keratinocytes stimulating their proliferation. The distribution and expression of TGF alpha and IL-1 alpha were examined in specimens of middle ear cholesteatoma by means of immunohistochemical methods using a monoclonal antibody against TGF alpha and a polyclonal one against IL-1 alpha. Normal retroauricular skin was stained for comparison. Staining for TGF alpha was consistently stronger in cholesteatoma epithelium than in normal epidermis, and encompassed all epithelial cell layers. Immune cells occurring in the stroma of cholesteatoma also reacted positively for TGF alpha. The intensity of staining for IL-1 alpha was markedly stronger in cholesteatoma tissue than in normal epidermis. All cellular layers of the squamous epithelium of cholesteatoma stained strongly and uniformly for IL-1 alpha, whereas the keratin layer was negative for IL-1 alpha. In the connective tissue beneath the cholesteatoma epithelium intensely positive cells were scattered between negative stromal cells. These data are consistent with autocrine stimulation of the squamous epithelium of cholesteatoma by TGF alpha and IL-1 alpha as well as with a paracrine stimulation by immune cells. Both factors contribute to the unrestrained growth of cholesteatoma in the middle ear cavity.

  12. Ductal barriers in mammary epithelium

    PubMed Central

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

    2013-01-01

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

  13. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

    2016-01-01

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

  14. [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

  15. 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 ...

  16. Distal esophageal spasm: an update.

    PubMed

    Achem, Sami R; Gerson, Lauren B

    2013-09-01

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

  17. 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.

  18. The Integrity of the Esophageal Mucosa. Balance Between Offensive and Defensive Mechanisms

    PubMed Central

    Orlando, Roy C.

    2010-01-01

    Heartburn is the most common and characteristic symptom of gastroesophageal reflux disease. It ultimately results from contact of refluxed gastric acid with nociceptors within the esophageal mucosa and transmission of this peripheral signal to the central nervous system for cognition. Healthy esophageal epithelium provides an effective barrier between refluxed gastric acid and esophageal nociceptors; but this barrier is vulnerable to attack and damage, particularly by acidic gastric contents. How gastric acid is countered by defensive elements within the esophageal mucosa is a major focus of this discussion. When the defense is successful, the subject is asymptomatic and when unsuccessful, the subject experiences heartburn. Those with heartburn commonly fall into one of three endoscopic types: nonerosive reflux disease, erosive esophagitis and Barrett's esophagus. Although what determines endoscopic type remains unknown; it is proposed herein that inflammation plays a key, modulating role. PMID:21126700

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

    PubMed Central

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

    2012-01-01

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

  20. Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

    PubMed Central

    Shen, Tian-Yun; Mei, Li-Li; Qiu, Yun-Tan; Shi, Zhi-Zhou

    2016-01-01

    The aim of the present study was to identify the candidate target genes of genomic aberrations in esophageal squamous cell carcinoma (ESCC). Array comparative genomic hybridization (CGH) and quantitative polymerase chain reaction were applied to analyze the copy number changes and expression level of candidate genes, respectively. Integrative analysis revealed that homozygous deletions of cyclin-dependent kinase inhibitor (CDKN) 2A and CDKN2B and gains of fascin actin-bundling protein 1 (FSCN1) and homer scaffolding protein 3 (HOMER3) occurred frequently in ESCC. The results demonstrated that the homozygous deletion of CDKN2A or CDKN2B was significantly associated with lymph node metastasis. Notably, the expression of CDKN2A and CDKN2B was lower in dysplasia than in normal esophageal epithelium. We also observed that the copy number increase of FSCN1 was significantly associated with pT, pN and pStage, and that the gain of HOMER3 was significantly linked with pN and pStage. We further revealed that FSCN1 and HOMER3 were overexpressed in ESCC, and that their overexpression was correlated with copy number increase. In conclusion, CDKN2A, CDKN2B, FSCN1 and HOMER3 are candidate cancer-associated genes and may play a tumorigenic role in ESCC.

  1. Identification of candidate target genes of genomic aberrations in esophageal squamous cell carcinoma

    PubMed Central

    Shen, Tian-Yun; Mei, Li-Li; Qiu, Yun-Tan; Shi, Zhi-Zhou

    2016-01-01

    The aim of the present study was to identify the candidate target genes of genomic aberrations in esophageal squamous cell carcinoma (ESCC). Array comparative genomic hybridization (CGH) and quantitative polymerase chain reaction were applied to analyze the copy number changes and expression level of candidate genes, respectively. Integrative analysis revealed that homozygous deletions of cyclin-dependent kinase inhibitor (CDKN) 2A and CDKN2B and gains of fascin actin-bundling protein 1 (FSCN1) and homer scaffolding protein 3 (HOMER3) occurred frequently in ESCC. The results demonstrated that the homozygous deletion of CDKN2A or CDKN2B was significantly associated with lymph node metastasis. Notably, the expression of CDKN2A and CDKN2B was lower in dysplasia than in normal esophageal epithelium. We also observed that the copy number increase of FSCN1 was significantly associated with pT, pN and pStage, and that the gain of HOMER3 was significantly linked with pN and pStage. We further revealed that FSCN1 and HOMER3 were overexpressed in ESCC, and that their overexpression was correlated with copy number increase. In conclusion, CDKN2A, CDKN2B, FSCN1 and HOMER3 are candidate cancer-associated genes and may play a tumorigenic role in ESCC. PMID:27698883

  2. Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

    PubMed Central

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

    2013-01-01

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

  3. Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice.

    PubMed

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

    2013-07-01

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

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

    PubMed

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

    1991-04-15

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

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

    PubMed

    Mittal, R K; McCallum, R W

    1988-09-01

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

  6. 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

  7. 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

  8. Primary Esophageal Intramural Squamous Cell Carcinoma Masquerading as a Submucosal Tumor: A Rare Presentation of a Common Disease

    PubMed Central

    Sonthalia, Nikhil; Jain, Samit S.; Surude, Ravindra G.; Pawar, Vinay B.; Udgirkar, Suhas; Rathi, Pravin M.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is the commonest primary malignant esophageal tumor, which typically presents as endoscopically visible surface mucosal ulcerations, irregularities, or polyploidal masses. We here report a rare case of primary ESCC with completely intramural growth under a normal looking intact nondysplastic surface squamous epithelium disguising as a submucosal tumor. Upper gastrointestinal endoscopy-guided mucosal biopsy was negative for malignancy. Endoscopic ultrasound (EUS) revealed a heteroechoic solid mass originating from the muscularis propria of the distal esophagus. Cytological study of EUS-guided fine needle aspiration from the mass was suggestive of squamous cell carcinoma, which was confirmed on immunohistochemistry. There was no evidence of metastatic origin of this tumor or continuous cancer involvement from the surrounding structures, including the head, neck, and lungs on bronchoscopy, computed tomography scan, and positron emission tomography scan. Exclusive intramural squamous cell carcinoma with normal overlying mucosa is an exceedingly rare presentation of primary ESCC with only four cases reported in the literature so far. A high index of suspicion is required by the gastroenterologists and pathologists in diagnosing these cases as these tumors closely mimic the mesenchymal submucosal tumors such as lipoma, leiomyoma, and gastrointestinal stromal tumors. EUS is an indispensable tool in making a preoperative diagnosis and therapeutic decision making. PMID:27721663

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

    ClinicalTrials.gov

    2016-11-02

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

  10. Ultrastructural study of grafted autologous cultured human epithelium.

    PubMed

    Aihara, M

    1989-01-01

    An electron microscopical study of grafted autologous cultured human epithelium is presented. Biopsy samples were collected from four patients with full thickness burns at 9 days, 6 weeks and 5-21 months after grafting of the cultured epithelium. By the sixth week after transplantation, grafted cultured epithelial sheets had developed to consist of 10 to 20 layers of cells and the epithelium showed distinct basal, spinous, granular and horny layers, and a patchy basement membrane had formed. Langerhans cells and melanocytes were identifiable. From 5 months onwards flat basal cells became oval, and oval keratohyalin granules in the keratinocytes also assumed a normal irregular shape. Membrane-coating granules in the keratinocytes increased in number. The fine structures of desmosomes also showed a normal mature appearance. Furthermore, complete extension of the basement membrane could be observed. The maturation of cultured human epithelium is complete by 5 months after grafting.

  11. 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

  12. High Mobility Group A proteins in esophageal carcinomas.

    PubMed

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

    2016-09-16

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

  13. [Minimal Change Esophagitis].

    PubMed

    Ryu, Han Seung; Choi, Suck Chei

    2016-01-25

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

  14. Imaging of esophageal cancer

    PubMed Central

    Iyer, R; DuBrow, R

    2004-01-01

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

  15. [Eosinophilic esophagitis: update 2012].

    PubMed

    Jo, Yunju

    2012-07-01

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

  16. 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.

  17. 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 ...

  18. 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 ...

  19. 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

  20. Congenital esophageal stenosis associated with esophageal atresia.

    PubMed

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

    2015-04-01

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

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

    PubMed

    Manfredi, Michael A

    2016-01-01

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

  2. 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

  3. 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.

  4. Characteristics of transient lower esophageal sphincter relaxation in humans.

    PubMed

    Mittal, R K; McCallum, R W

    1987-05-01

    Transient lower esophageal sphincter relaxations (TLESR) were studied in 10 normal healthy subjects. Electrical activity of mylohyoid muscle measured by an electromyogram (MEMG), pressures from pharynx, three esophageal sites, lower esophageal sphincter, and stomach were simultaneously recorded for 1 h, while fasting and 3 h after an 850 kcal meal. Reflux of acid into esophagus and/or occurrence of belching accompanying a TLESR was also monitored. TLESRs occurred with an equal frequency in fasting and postprandial state (6.2 vs. 6.4 h). However, frequency of an acid reflux during a TLESR was much greater postprandially than after fasting (44.8 vs. 9.6%). Belching coincided with 8% of TLESRs. A small MEMG complex and a small pharyngeal complex were present at onset of TLESR in 41.6 and 26.9% of instances, respectively. TLESRs were then categorized as either postswallow, if it occurred within 10 s of a preceding swallow-induced LES relaxation, or isolated, if its onset to previous swallow was greater than 10 s. Esophageal contractions were noticed at onset of 84% of isolated TLESRs. When present at two distal sites, this contraction was always of a simultaneous nature. Esophageal contractions at onset of postswallow TLESR were less frequent (33.3%) but when present were usually observed at the proximal esophageal site. At completion of a TLESR, the LES never recovered without an associated esophageal contraction, the latter was either swallow mediated or a spontaneous simultaneous esophageal contraction. Our data indicate that 1) MEMG and pharyngeal motor events may accompany TLESRs; and 2) esophageal contraction frequently heralds the onset, and it always occurs at completion of a TLESR.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. 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.

  6. Esophageal phytobezoar in a horse.

    PubMed

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

    1987-12-01

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

  7. National Esophageal Atresia Register.

    PubMed

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

    2015-12-01

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

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

    PubMed Central

    2009-01-01

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

  9. Suppression of N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis by dietary feeding of 1'-acetoxychavicol acetate.

    PubMed

    Kawabata, K; Tanaka, T; Yamamoto, T; Ushida, J; Hara, A; Murakami, A; Koshimizu, K; Ohigashi, H; Stoner, G D; Mori, H

    2000-02-01

    The modifying effects of 1'-acetoxychavicol acetate (ACA) on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis were investigated in male F344 rats. At 5 weeks of age, all test animals, except those given the test chemical alone, and the control rats received s.c. injections of NMBA (0.5 mg/kg body weight/injection, three times per week) for 5 weeks. At the termination of the study (20 weeks), 75% of rats treated with NMBA alone had esophageal neoplasms (papillomas). However, the groups given a dose of 500 ppm ACA during the initiation phase developed a significantly reduced incidence of tumors (29%; P<0.01). Exposure to ACA (500 ppm) during the post-initiation phase also decreased the frequency of the tumors (38%; P<0.05). A reduction of the incidence of preneoplastic lesions (hyperplasia or dysplasia) was obtained when ACA was administered in the initiation phase (P<0.01). Cell proliferation in the esophageal epithelium, determined by assay of proliferating cell nuclear antigen (PCNA), was lowered by ACA (P<0.05). Blood polyamine contents in rats given NMBA and the test compound were also smaller than those of rats given the carcinogen (P<0.05). These findings suggest that dietary ACA is effective in inhibiting the development of esophageal tumors by NMBA when given during the initiation or post-initiation phase, and such inhibition is related to suppression of cell proliferation in the esophageal epithelium.

  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. Assessing esophageal dysphagia.

    PubMed

    Kruger, Danielle

    2014-05-01

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

  12. Flow cytometric DNA analysis of corneal epithelium.

    PubMed

    Burns, E R; Roberson, M C; Brown, M F; Shock, J P; Pipkin, J L; Hinson, W G; Anson, J F

    1990-03-01

    We have modified an existing technique in order to perform DNA analysis by flow cytometry (FCM) of corneal epithelium from the mouse, rat, chicken, rabbit, and human. This protocol permitted an investigation of human corneal scrapings from several categories: normal, aphakic bullous keratopathy (ABK), keratoconus (KC), Fuch's dystrophy, edema, epithelial dysplasia, and lipid degeneration. No abnormal characteristic cell-kinetic profile was detected when averaged DNA histograms were compared statistically between the normal and either ABK, KC, edema, or Fuch's dystrophy groups. Abnormal DNA histograms were recorded for cell samples that were taken 1) from three individuals who had epithelial dysplasia and 2) from one individual diagnosed with lipid degeneration. The former condition was characterized by histograms that had a subpopulation of cells with an aneuploid amount of DNA or had higher than normal percentages of cells in the S and G2 + M phases of the cell cycle. Corneal cells from the patient who had lipid degeneration had an abnormally high percentage of cells in the G2 + M phases of the cell cycle. The availability of accurate DNA flow cytometric analysis of corneal epithelium allows further studies on this issue from both experimental and clinical situations.

  13. 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

  14. Magnification endoscopy in esophageal squamous cell carcinoma: a review of the intrapapillary capillary loop classification

    PubMed Central

    Inoue, Haruhiro; Kaga, Makoto; Ikeda, Haruo; Sato, Chiaki; Sato, Hiroki; Minami, Hitomi; Santi, Esperanza Grace; Hayee, Bu’Hussain; Eleftheriadis, Nikolas

    2015-01-01

    Recent developments in image-enhancement technology have enabled clear visualization of the microvascular structure of the esophageal mucosa. In particular, intrapapillary capillary loops (IPCLs) are observed as brown loops on magnification endoscopy with narrow-band imaging (NBI). IPCLs demonstrate characteristic morphological changes according to the structural irregularity of esophageal epithelium and cancer infiltration, summarized in the IPCL classification. In this review, the process from the first endoscopic description of IPCLs to the eventual development of the IPCL classification is described and discussed, particularly focusing on early stage squamous cell carcinoma of the esophagus. PMID:25608626

  15. 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

  16. 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.

  17. 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.

  18. Anginal pain of esophageal origin: clinical presentation, prevalence, and prognosis.

    PubMed

    Davies, H A

    1992-05-27

    Since 1768, when Heberden recognized a relationship of angina pectoris with eating, the close resemblance between angina-like pain of esophageal and cardiac origin has led to diagnostic confusion, with the role of the esophagus being, in turn, over- and underemphasized as a cause of symptoms. Although the classic features of angina do not distinguish the origin of the pain, certain other symptoms may identify esophageal pain. These include an inconsistent correlation of exercise with pain, periods of prolonged remission, provocation of pain by posture, association with other esophageal symptoms, relief by antacids, radiation of pain down the right arm and into the back, occurrence of pain at night, continuation of pain as a background ache, and relief from nitroglycerine delayed by 10 minutes or longer. However, while certain symptoms may alert the clinician to the possibility that angina-like pain is due to esophageal disease, no single symptom or combination of symptoms is infallible; there is no alternative to careful assessment. Esophageal disease accounts for the greatest number of patients with chest pain of unknown origin. The prevalence of angina-like esophageal pain in unselected emergency admissions with suspected myocardial infarction is 10-20%. Approximately one third or more of patients with angina and normal coronary arteries have esophageal problems. We have followed patients with angina-like esophageal pain for 9 years. Although prognosis remains good, confirming the original noncardiac diagnosis, greater than 80% of patients continue to have chest pain of undiminished intensity, and half are limited in their ability to work. Reassurance appeared to have one beneficial result: Patients were less likely to consult a physician after a positive diagnosis had been made.

  19. 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

  20. Effect of gastroesophageal reflux on esophageal speech.

    PubMed

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

    1983-12-01

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

  1. 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

  2. Safrole-DNA adducts in tissues from esophageal cancer patients: clues to areca-related esophageal carcinogenesis.

    PubMed

    Lee, Jang-Ming; Liu, Tsung-Yung; Wu, Deng-Chyang; Tang, Hseau-Chung; Leh, Julie; Wu, Ming-Tsang; Hsu, Hsao-Hsun; Huang, Pei-Ming; Chen, Jin-Shing; Lee, Chun-Jean; Lee, Yung-Chie

    2005-01-01

    Epidemiological studies have demonstrated that areca quid chewing can be an independent risk factor for developing esophageal cancer. However, no studies are available to elucidate the mechanisms of how areca induces carcinogenesis in the esophagus. Since the areca nut in Taiwan contains a high concentration of safrole, a well-known carcinogenic agent, we analyzed safrole-DNA adducts by the 32P-postlabelling method in tissue specimens from esophageal cancer patients. In total, we evaluated 47 patients with esophageal cancer (16 areca chewers and 31 non-chewers) who underwent esophagectomy at the National Taiwan University Hospital between 1996 and 2002. Of the individuals with a history of habitual areca chewing (14 cigarette smokers and two non-smokers), one of the tumor tissue samples and five of the normal esophageal mucosa samples were positive for safrole-DNA adducts. All patients positive for safrole-DNA adducts were also cigarette smokers. Such adducts could not be found in patients who did not chew areca, irrespective of their habits of alcohol consumption or cigarette smoking (p<0.001, comparing the areca chewers with non-chewers). The genotoxicity of safrole was also tested in vitro in three esophageal cell lines and four cultures of primary esophageal keratinocytes. In two of the esophageal keratinocyte cultures, adduct formation was increased by treatment with safrole after induction of cytochrome P450 by 3-methyl-cholanthrene. This paper provides the first observation of how areca induces esophageal carcinogenesis, i.e., through the genotoxicity of safrole, a component of the areca juice.

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

    PubMed

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

    2001-02-01

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

  4. Eosinophilic Esophagitis: Epithelial Mesenchymal Transition Contributes to Esophageal Remodeling and Reverses with Treatment

    PubMed Central

    Kagalwalla, Amir F.; Akhtar, Noorain; Woodruff, Samantha A.; Rea, Bryan A.; Masterson, Joanne C.; Mukkada, Vincent; Parashette, Kalyan R.; Du, Jian; Fillon, Sophie; Protheroe, Cheryl A.; Lee, James J.; Amsden, Katie; Melin-Aldana, Hector; Capocelli, Kelley E.; Furuta, Glenn T.; Ackerman, Steven J.

    2012-01-01

    Background Mechanisms underlying esophageal remodeling with subepithelial fibrosis in eosinophilic esophagitis (EoE) have not been delineated. Objectives To explore a role for Epithelial Mesenchymal Transition (EMT) in EoE, and whether EMT resolves with treatment. Methods Esophageal biopsies from 60 children were immunostained for epithelial (cytokeratin) and mesenchymal (vimentin) EMT biomarkers, and EMT quantified. Subjects studied had EoE (n=17), EoE-indeterminate (n=15), GERD (n=7) or normal esophagus (n=21). EMT was analyzed for relationships to diagnosis, eosinophils, and indices of subepithelial fibrosis, eosinophil peroxidase (EPX) and TGF-β immunostaining. EMT was assessed in pre- and post-treatment biopsies from 18 EoE subjects treated with elemental diet, six-food elimination diet, or topical corticosteroids (n=6/group). Results TGF-β1 treatment of esophageal epithelial cells in vitro for 24hrs induced upregulation of mesenchymal genes characteristic of EMT including N-cadherin (3.3-fold), vimentin (2.1-fold) and fibronectin (7.5-fold). EMT in esophageal biopsies was associated with EoE (or indeterminate EoE), but not GERD or normal esophagus, and was correlated to eosinophils (r=0.691), EPX (r=0.738) and TGF-β (r=0.520) immunostaining, and fibrosis (r=0.644) indices. EMT resolved with EoE treatments that induced clinicopathologic remission with reduced eosinophils. EMT decreased significantly post-treatment by 74.1% overall in the 18 treated EoE subjects; pre- vs. post-treatment EMT scores–3.17±0.82 vs. 0.82±0.39 (p<0.001), with similar decreases within treatment groups. Pre-/post-treatment EMT was strongly correlated with eosinophils for combined (r=0.804, p< 0.001) and individual treatment groups. Conclusions EMT likely contributes to subepithelial fibrosis in EoE, resolves with treatments that decrease esophageal inflammation, and its resolution correlates with decreased numbers of esophageal eosinophils. PMID:22465212

  5. The influence of age, smoking, antiretroviral therapy, and esophagitis on the local immunity of the esophagus in patients with AIDS.

    PubMed

    Cavellani, Camila Lourencini; Gomes, Nayara Cândida; de Melo e Silva, Ana Teresa; Silva, Renata Beatriz; Ferraz, Mara Lúcia Fonseca; Faria, Humberto Aparecido; Corrêa, Rosana Rosa Miranda; Teixeira, Vicente de Paula Antunes; Rocha, Laura Penna

    2013-01-01

    Studies have shown immunological and morphological alterations in the esophagus during the course of AIDS. Esophageal postmortem samples of 22 men with AIDS autopsied in a teaching hospital between 1982 and 2009 were collected. We carried out revision of the autopsy reports and medical records, morphometric analysis (Image J and KS-300 Kontron-Zeiss), and immunohistochemical (anti-S100, anti-IgA, anti-IgG, and anti-IgM) analysis of the esophagus. In accordance with most of the parameters evaluated, age and the smoking habit harmed the esophageal local immunity, whereas the use of antiretroviral therapy improved the immune characteristics of this organ. Patients with esophagitis also presented immunological fragility of the esophagus. This leads to the conclusion that alterations in the esophageal epithelium of patients with AIDS are not only caused by direct action of HIV but also the clinical and behavioral characteristics of the patient.

  6. Eosinophilic esophagitis: current treatment.

    PubMed

    Redd, Matthew; Schey, Ron

    2013-03-01

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

  7. Esophageal carcinoma: CT findings

    SciTech Connect

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

    1985-04-01

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

  8. 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

  9. Staging Early Esophageal Cancer.

    PubMed

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

    2016-01-01

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

  10. Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins.

    PubMed

    Chen, Xin; Oshima, Tadayuki; Shan, Jing; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

    2012-07-15

    Reflux of acid and bile acids contributes to epithelial tissue injury in gastro-esophageal reflux disease. However, the influence of refluxed material on human esophageal stratified epithelial barrier function and tight junction (TJ) proteins has not been fully elucidated. Here, we investigated the influence of acid and bile acids on barrier function and TJ protein distribution using a newly developed air-liquid interface (ALI) in vitro culture model of stratified squamous epithelium based on primary human esophageal epithelial cells (HEECs). Under ALI conditions, HEECs formed distinct epithelial layers on Transwell inserts after 7 days of culture. The epithelial layers formed TJ, and the presence of claudin-1, claudin-4, and occludin were detected by immunofluorescent staining. The NP-40-insoluble fraction of these TJ proteins was significantly higher by day 7 of ALI culture. Exposure of HEECs to pH 2, and taurocholic acid (TCA) and glycocholic acid (GCA) at pH 3, but not pH 4, for 1 h decreased transepithelial electrical resistance (TEER) and increased paracellular permeability. Exposure of cell layers to GCA (pH 3) and TCA (pH 3) for 1 h also markedly reduced the insoluble fractions of claudin-1 and -4. We found that deoxycholic acid (pH 7.4 or 6, 1 h) and pepsin (pH 3, 24 h) significantly decreased TEER and increased permeability. Based on these findings, ALI-cultured HEECs represent a new in vitro model of human esophageal stratified epithelium and are suitable for studying esophageal epithelial barrier functions. Using this model, we demonstrated that acid, bile acids, and pepsin disrupt squamous epithelial barrier function partly by modulating TJ proteins. These results provide new insights into understanding the role of TJ proteins in esophagitis.

  11. [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

  12. [Eosinophilic esophagitis--pathogenesis, clinical presentation and therapeutic management].

    PubMed

    von Arnim, U; Mönkemüller, K; Malfertheiner, P; Straumann, A

    2007-12-01

    Eosinophilic esophagitis (EE) is a relatively new, chronic, TH 2-type allergic inflammation of the esophagus. EE occurs more frequently in men. Allergic diseases such as asthma or atopic dermatitis are present in 50-70 % of patients or their relatives. In adults, the most common presenting symptom of EE is dysphagia, with or without food bolus impaction. Endoscopic findings of EE include mucosal furrows, corrugated or concentric rings or ridges in the esophagus ("feline esophagus"), with or without tiny whitish exudates. The diagnosis is confirmed by the observation of high counts of eosinophils in the esophageal epithelium (at least 24 /HPF). The cornerstones of medical therapy are either topical or systemic corticosteroids. Additional therapies included leukotriene receptor antagonists (montelukast) and IL-5 blockers (Mepolizumab). Complications of EE such as esophageal strictures should be carefully dilated using either bougies or a balloon. Currently it is still not known whether the late complications of EE can be prevented by the use of anti-inflammatory agents and this can only be demonstrated through further long-term follow-up studies.

  13. Enzymatic digestion of esophageal meat impaction. A study of Adolph's Meat Tenderizer.

    PubMed

    Goldner, F; Danley, D

    1985-05-01

    While a solution of Adolph's Meat Tenderizer (AMT) is commonly used to treat esophageal meat impaction, few studies describe its clinical effects. We examined AMT with regard to (1) its papain activity; (2) its ability to digest meat cubes in vitro; and (3) its effect on rabbit esophageal mucosa. A standard papain assay was developed against which the activity of AMT was compared. Proteolytic activity was detected in AMT only when the papain activators, 0.02 M cysteine and 0.008 M EDTA, were added to the system. Meat cubes incubated in AMT solution exhibited no evidence of digestion as determined by protein release or change in sample weight. A solution of AMT had no adverse effect on normal esophageal mucosa in rabbits, but significantly increased esophagitis when infused onto previously inflamed mucosa. We conclude that AMT solution has no inherent capacity to digest or to reduce the size of an impacted meat bolus, and may, in fact, worsen existing esophagitis.

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

    SciTech Connect

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

    1985-05-01

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

  15. 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.

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

    PubMed

    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

  17. 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

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

    PubMed

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

    2015-01-01

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

  19. Intraluminal esophageal diverticulum.

    PubMed

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

    1990-02-01

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

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

    PubMed

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

    2016-01-01

    The defect of esophagus after surgical excision in patients is usually replaced by autologous stomach, jejunum, or colon. The operation brings severe trauma and complications. Using artificial esophagus to replace the defect in situ can reduce the operative trauma, simplify the operative procedures, and decrease the influence to digestive function. A variety of experiments have been designed for developing a practical artificial esophagus. Nevertheless, a safe and reliable artificial esophagus is not yet available. The objective is to evaluate the possibility of the artificial esophagus made of non-degradable polyurethane materials being used in reconstruction of the segmental defect of cervical esophagus in beagles, observe the regeneration of esophageal tissue, and gather experience for future study. The cervical esophageal defects in 13 beagles were designed to 2-cm long and were constructed by the artificial esophagus made of non-degradable polyurethane materials. Nutrition supports were given after the operation. The operative mortality, anastomotic leakage, migration of artificial esophagus, and dysphagia were followed up. The regeneration of the esophageal tissues was evaluated by histopathology and immunohistochemical labeled streptavidin-biotin method. The surgical procedures were successfully completed in all beagles, and 12-month follow-ups were done. Only one beagle died of severe infection, and all others survived until being killed. The anastomotic leakage occurred in nine beagles, most of them (8/9) were cured after supportive therapy. The migration of artificial esophagus occurred in all 12 surviving beagles, and one artificial esophagus stayed in situ after migration. All 12 surviving beagles showed dysphagia with taking only fluid or soft food. No beagle died of malnutrition. The neo-esophagus was composed of granulation tissue, and the inner surface was covered by epithelium in 2-3 months completely. But the inner surface of neo-esophagus with

  1. [Marshmallow for investigating functional disturbances of the esophageal body].

    PubMed

    Keren, S; Argaman, E

    1992-09-01

    Manometric studies using water boluses do not always demonstrate disturbances in esophageal motility. We tested the use of a marshmallow bolus to induce abnormal manometric patterns in patients with dysphagia in whom manometric studies using water boluses were normal or nearly so. The study group included 12 normal volunteers and 22 patients with dysphagia and nearly normal manometric studies. Pressure was recorded along the esophageal body using 10 "wet" swallows followed by 10 "solid" swallows of marshmallow. In normal subjects there were fewer abnormal contractions after solid swallows than after wet swallows. In 15 patients solid swallows induced abnormal motility patterns which were not observed after wet swallows. The probability of inducing abnormal contractions in patients after solid swallows is significantly greater than after wet swallows (p < 0.0001). Solid swallowing is therefore useful in evaluating functional disturbances of the esophagus in patients with dysphagia.

  2. 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

  3. 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

  4. 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

  5. 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)

  6. 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.

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Esophageal space-occupying lesion caused by Ascaris lumbricoides

    PubMed Central

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

    2012-01-01

    Ascaris lumbricoides is the largest intestinal nematode parasite of man, which can lead to various complications because of its mobility. As the esophagus is not normal habitat of Ascaris, the report of esophageal ascariasis is rare. An old female presented with dysphagia after an intake of several red bean buns and haw jellies. The barium meal examination revealed a spherical defect in the lower esophagus. Esophageal bezoar or esophageal carcinoma was considered at the beginning. The patient fasted, and received fluid replacement treatment as well as some oral drugs such as proton pump inhibitor and sodium bicarbonate. Then upper gastrointestinal endoscopy was done to further confirm the diagnosis and found a live Ascaris lumbricoides in the gastric antrum and two in the duodenal bulb. The conclusive diagnosis was ascariasis. The esophageal space-occupying lesion might be the entangled worm bolus. Anthelmitnic treatment with mebendazole improved 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

  16. 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

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

    PubMed

    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 Mucaine(R) 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

  18. 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.

  19. 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

  20. Cutaneous Metastases From Esophageal Adenocarcinoma

    PubMed Central

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

    2015-01-01

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

  1. 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

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

    PubMed

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

    2015-09-16

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

  3. [Epithelium and anal glands in rectal pouches and fistula. Histologic studies of swine with congenital anal atresia].

    PubMed

    Lambrecht, W; Kluth, D; Lierse, W

    1989-02-01

    The epithelial coating of the rectal pouch and fistula was studied morphologically in 33 newborn piglets with high and low forms of anal atresia and was found to be similar to the epithelial coating of the anal canal in normal piglets: the typical epithelium of the rectum changed its character into transitional epithelium at the region of the internal sphincter which surrounded the fistulae in all animals. In the caudal part of the fistula the transitional epithelium was followed by squamous epithelium. Only in male piglets with deformities and recto-urethral fistulae no squamous epithelium was found. In these cases transitional epithelium covered all parts of the fistula and the region of the internal sphincter. Anal glands were found in all animals, with or without anorectal malformations. They always invaded the internal sphincter. According to our morphological studies the fistula in anorectal malformations represents an ectopic anal canal.

  4. [Experimental gene therapy using p21/WAF1 gene in esophageal squamous cell carcinoma--adenovirus infection and gene gun technology].

    PubMed

    Fujii, T; Tanaka, Y; Tanaka, T; Matono, S; Sueyoshi, S; Fujita, H; Shirouzu, K; Kato, S; Yamana, H

    2001-10-01

    p21/WAF1 (p21) inhibits the activity of the cyclin/cdk complex and controls the G1 to S cell phase transition. In the present study, we used a recombinant adenoviral approach and gene gun technology to introduce p21 into esophageal cancer cells in order to assess the effect of p21 on cell growth. Infection with the p21 adenovirus (AdV) using gene gun technology resulted in inhibition of TE9 and KE3 cell growth. The levels of involucrin, which is a marker of squamous epithelium differentiation, markedly increased at 48 h and 72 h after p21 AdV infection in TE9 cells. These results indicate that p21 plays an important role in esophageal cancer cell proliferation. Overexpression of the p21 gene can inhibit cell growth and induce differentiation in esophageal cancer cells. p21 gene therapy may prove beneficial in the treatment of esophageal cancer.

  5. 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 ...

  6. 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...

  7. 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...

  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, 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...

  10. 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

  11. Is There any Association Between Passive Smoking and Esophagitis in Pediatrics?

    PubMed Central

    Monajemzadeh, Maryam; Haghi-Ashtiani, Mohammad-Taghi; Soleymani, Roohallah; Shams, Sedigheh; Taleb, Shayandokht; Motamed, Farzaneh; Najafi, Mehri; Abbasi, Ata

    2013-01-01

    Objective Exposure to environmental tobacco smoke (ETS) is one of the major factors of predisposing children to develop several hazardous health problems. We decided to investigate the association between nicotinine, one of the nicotine metabolites and esophagitis in children with gastroesophageal reflux disease (GERD). Methods In a case control study 46 children suffering from esophagitis referred to endoscopy ward were recruited. The control group consisted of 45 healthy children. Urine samples were collected and urinary cotinine level (UCL) measured. Findings The mean age of esophagitis and control groups were 5.11±2.93 and 6.72±2.8 respectively. Sixty children were passive smokers; 31 of them had non-smoker parents. In control group, 32 (71.1%) children and in esophagitis group 29 (63%) children had non-smoker parents. The mean value of UCL in patients suffering from esophagitis was significantly higher than those in normal group (P=0.04, 24.98±6.4 ng/ml vs. 15.16 ± 3.9 ng/ml). Considering 50ng/ml as a cutoff point for UCL, it was significantly higher in passive smoker group than in non smoker group (P=0.02). The mean cotinine level differed significantly in esophagitis and control group. Conclusion Our results indicate the increased risk of developing esophagitis in children with ETS exposure. PMID:23724182

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

    PubMed Central

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

    2014-01-01

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

  13. 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. Calcium carbonate antacids alter esophageal motility in heartburn sufferers.

    PubMed

    Rodriguez-Stanley, Sheila; Ahmed, Tanveer; Zubaidi, Sattar; Riley, Susan; Akbarali, Hamid I; Mellow, Mark H; Miner, Philip B

    2004-01-01

    Chewed calcium carbonate (CaCO3) rapidly neutralizes esophageal acid and may prevent reflux, suggesting another mechanism of action independent of acid neutralization. Calcium is essential for muscle tone. Our aim was to determine if luminal calcium released from chewed antacids improved esophageal motor function in heartburn sufferers. Esophageal manometry and acid clearance (swallows and time to raise esophageal pH to 5 after a 15-ml 0.1 N HCl bolus) were performed in 18 heartburn sufferers before and after chewing two Tums EX (1500 mg CaCO3, 600 mg calcium). Subjects with hypertensive esophageal contractions or hypertensive lower esophageal sphincter pressure (LESP) were excluded. Subjects with normal to low LESP were included. Differences between parameters were determined by two-tailed paired t-tests, P < 0.05. Proximal esophageal contractile amplitude was significantly increased after CaCO3 (47.18 vs 52.97 mm Hg; P = 0.02), distal onset velocity was significantly decreased after CaCO3 (4.34 vs 3.71 cm/sec; P = 0.02), and acid clearance was significantly increased 30 min after CaCO3 (20.35 vs 11.7 swallows, [P < 0.005] and 12.19 vs 6.29 min [P < 0.007]). LESP was not altered after CaCO3 (22.70 vs 23.79 mm Hg; P = 0.551), however, LESP increased in 9 of 18 subjects. Depth of LES relaxation, medial and distal esophageal contractile amplitude, and duration of contractions were not altered by CaCO3. CaCO3 did not alter salivary secretion and pH in a subset of these subjects, and CaCO3 with secreted saliva did not neutralize a 15-ml acid bolus. The Ca2+ released after chewing of CaCO3 antacids may be partially responsible for the reduction of heartburn by significantly improving initiation of peristalsis and acid clearance.

  15. A Comprehensive Review of Esophageal Stents

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. 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. [Hormone-mediated reactions in the endosalpinx epithelium].

    PubMed

    Glukhovets, B I; Ukhov, Iu I; Lebedev, S S; Plastun, G A; Bulaeva, V P

    1983-07-01

    The epithelium of normal uterine tubes resected in 38 young women of the child-bearing age during the periods of the maximal physiological fluctuations of the ovarian steroid hormones levels has been studied. The correlative dependence between the morphometrical data and the results of quanitative biochemical analysis of the estrogen excretion has been investigated. The morphometric method reliably reflects the hormone-dependent variabilities of the oviduct epithelium and makes it possible to perform an objective morphological evaluation of the ovarian functional activity. The height and specific density of cells in the epithelial layer, portion of the aciliary cells and nuclear volume of the ciliary cells are the most important for diagnosis as compared to the excretory level of the estrogenic hormones. PMID:6625907

  19. 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

  20. Genetic landscape of esophageal squamous cell carcinoma.

    PubMed

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

    2014-10-01

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

  1. Eosinophilic esophagitis in an octogenarian

    PubMed Central

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

    2016-01-01

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

  2. Airway responsiveness: role of inflammation, epithelium damage and smooth muscle tension.

    PubMed

    Gourgoulianis, K I; Domali, A; Molyvdas, P A

    1999-01-01

    The purpose of this study was the effect of epithelium damage on mechanical responses of airway smooth muscles under different resting tension. We performed acetylcholine (ACh) (10(-5) M)-induced contraction on tracheal strips from 30 rabbits in five groups (0.5, 1, 1.5, 2 and 2.5 g) before and after epithelium removal. At low resting tension (0.5-1.5 g), the epithelium removal decreased the ACh-induced contractions. At 2 g resting tension, the epithelium removal increased the ACh-induced contractions of airways with intact epithelium about 20%. At 2.5 g resting tension, the elevation of contraction is about 25% (P<0.01). Consequently, after epithelium loss, the resting tension determines the airway smooth muscles responsiveness. In asthma, mediators such as ACh act on already contracted inflammatory airways, which results in additional increase of contraction. In contrast, low resting tension, a condition that simulates normal tidal breathing, protects from bronchoconstriction even when the epithelium is damaged. PMID:10704081

  3. 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

  4. [Caustic esophagitis: surgical management].

    PubMed

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

    1990-01-01

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

  5. 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

  6. Use of gastrotomy to relieve esophageal obstruction in a horse.

    PubMed

    Orsini, J A; Dikes, N; Ruggles, A; Charlton, C; Perry, R

    1991-01-15

    Esophageal obstruction of 1 week's duration in a gelding was diagnosed by contrast radiography and esophagoscopy. A food bolus was found at the junction of the caudal thoracic portion of the esophagus and the cardia. A gastrotomy was performed through a cranial abdominal incision and a phytobezoar was manually broken down and removed. The gelding was started on complete pellet food and water on the fifth day after surgery. The horse remained clinically normal more than 1 year after surgery.

  7. Biochemical studies of the tracheobronchial epithelium

    SciTech Connect

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

    1984-06-01

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

  8. Hyperthermochemoradiotherapy for esophageal cancer (review).

    PubMed

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

    1992-01-01

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

  9. 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

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

    PubMed Central

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

    2016-01-01

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

  11. 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.

  12. 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

  13. 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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

  16. Dietary treatment of eosinophilic esophagitis.

    PubMed

    Gonsalves, Nirmala; Kagalwalla, Amir F

    2014-06-01

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

  17. Imaging and Clinicopathologic Features of Esophageal Gastrointestinal Stromal Tumors

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    ClinicalTrials.gov

    2016-07-30

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

  20. Integrin Beta 1 Suppresses Multilayering of a Simple Epithelium

    PubMed Central

    Chen, Jichao; Krasnow, Mark A.

    2012-01-01

    Epithelia are classified as either simple, a single cell layer thick, or stratified (multilayered). Stratified epithelia arise from simple epithelia during development, and transcription factor p63 functions as a key positive regulator of epidermal stratification. Here we show that deletion of integrin beta 1 (Itgb1) in the developing mouse airway epithelium abrogates airway branching and converts this monolayer epithelium into a multilayer epithelium with more than 10 extra layers. Mutant lung epithelial cells change mitotic spindle orientation to seed outer layers, and cells in different layers become molecularly and functionally distinct, hallmarks of normal stratification. However, mutant lung epithelial cells do not activate p63 and do not switch to the stratified keratin profile of epidermal cells. These data, together with previous data implicating Itgb1 in regulation of epidermal stratification, suggest that the simple-versus-stratified developmental decision may involve not only stratification inducers like p63 but suppressors like Itgb1 that prevent simple epithelia from inappropriately activating key steps in the stratification program. PMID:23285215

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

    PubMed Central

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

    2015-01-01

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

  2. The junctional epithelium originates from the odontogenic epithelium of an erupted tooth.

    PubMed

    Yajima-Himuro, Sara; Oshima, Masamitsu; Yamamoto, Gou; Ogawa, Miho; Furuya, Madoka; Tanaka, Junichi; Nishii, Kousuke; Mishima, Kenji; Tachikawa, Tetsuhiko; Tsuji, Takashi; Yamamoto, Matsuo

    2014-05-02

    The junctional epithelium (JE) is an epithelial component that is directly attached to the tooth surface and has a protective function against periodontal diseases. In this study, we determined the origin of the JE using a bioengineered tooth technique. We transplanted the bioengineered tooth germ into the alveolar bone with an epithelial component that expressed green fluorescence protein. The reduced enamel epithelium from the bioengineered tooth fused with the oral epithelium, and the JE was apparently formed around the bioengineered tooth 50 days after transplantation. Importantly, the JE exhibited green fluorescence for at least 140 days after transplantation, suggesting that the JE was not replaced by oral epithelium. Therefore, our results demonstrated that the origin of the JE was the odontogenic epithelium, and odontogenic epithelium-derived JE was maintained for a relatively long period.

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

    ClinicalTrials.gov

    2015-12-10

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

  4. Esophageal manifestations of celiac disease.

    PubMed

    Lucendo, A J

    2011-09-01

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

  5. Esophageal Cancer Risk Prediction Models

    Cancer.gov

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

  6. Thymus epithelium induces tissue-specific tolerance

    PubMed Central

    1993-01-01

    Most current models of T cell development include a positive selection step in the thymus that occurs when T cells interact with thymic epithelium and a negative selection step after encounters with bone marrow-derived cells. We show here that developing T cells are tolerized when they recognize antigens expressed by thymic epithelium, that the tolerance is tissue specific, and that it can occur by deletion of the reactive T cells. PMID:8459209

  7. Teaching normal birth, normally.

    PubMed

    Hotelling, Barbara A

    2009-01-01

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

  8. WISP-1 contributes to fractionated irradiation-induced radioresistance in esophageal carcinoma cell lines and mice.

    PubMed

    Li, Wen-Feng; Zhang, Li; Li, Hai-Ying; Zheng, Si-Si; Zhao, Liang

    2014-01-01

    Cancer cells that survive fractionated irradiation can be radioresistant and cause tumor recurrence. However, the molecular mechanisms underlying the development of radioresistance in cancer cells remain elusive. The aim of this study was to investigate the role of WISP-1 in the development of radioresistance in esophageal carcinoma during fractionated irradiation. Radioresistant esophageal cancer cells were generated from normal esophageal cancer cells via fractionated irradiation, and expression levels of related proteins were determined by Western blot. Radiosensitivity of cells was established by clonogenic cell survival assays, and cell cycle distribution was evaluated by flow cytometry. Protein distributions were determined by immunofluorescence, and cell toxicity was evaluated by cell counting kit-8 assays. In vivo validations were performed in a xenograft transplantation mouse model. Our data indicate that WISP-1 plays an important role in the development of radioresistance in esophageal cancer cells during fractionated irradiation. The overexression of WISP-1 in esophageal cancer cells was associated with radioresistance. Depletion of extracellular WISP-1 by antibody neutralizing reversed radioresistance and directly induced mitotic catastrophe resulting in cell death. WISP-1 may be a candidate therapeutic target in the treatment of recurrent esophageal carcinoma after radiotherapy.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  10. Computed tomography for staging esophageal and gastroesophageal cancer: reevaluation

    SciTech Connect

    Thompson, W.M.; Halvorsen, R.A.; Foster, W.L. Jr.; Williford, M.E.; Postlethwait, R.W.; Korobkin, M.

    1983-11-01

    A reevaluation of computed tomography (CT) for staging carcinoma of the esophagus and gastroesophageal junction was performed in 76 patients. For comparison 26 patients without carcinoma of the esophagus with a normal mediastinum at surgery were included in the evaluation. Four radiologists evaluated the CT scans without knowledge of the diagnosis. After determining if there was an adequate amount of fat, they were asked to evaluate each case for the presence or absence of local invasion and distant metastases. The radiologists correctly identified all 26 normal patients. Eighteen of the 76 carcinoma had a paucity of fat, but only six were thought to have truly indeterminate scans. CT correctly identified 40 of the 44 esophageal carcinoma patients with mediastinal invasion and 11 of the 15 patients without invasion (accuracy 88%). CT correctly identified 15 of 19 patients with distant abdominal metastases and 28 of 30 patients without metastases (accuracy 88%). CT was only 50% accurate in predicting the presence or absence of invasion in the 12 patients with gastroesophageal junction tumors and only 58% accurate in predicting distant metastases. CT correctly staged 46(94%) of 49 patients with esophageal carcinoma but only five (42%) of 12 patients with gastroesophageal junction tumors. These results confirm that CT should be used as a major staging method in all patients with esophageal carcinoma.

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

    PubMed Central

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

    2012-01-01

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

  12. The Changing Face of Esophageal Cancer

    PubMed Central

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

    2010-01-01

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

  13. [Importance of upper digestive endoscopy using lugol dye solution for the diagnosis of superficial esophageal cancer and dysplasia in patients with head and neck neoplasms].

    PubMed

    Tincani, A J; Brandalise, N; Andreollo, N A; Lopes, L R; Montes, C G; Altemani, A; Martins, A S

    2000-01-01

    Head and neck cancer has a high incidence in Brazil, with cancer of the oral cavity being one of the five most common cancers among Brazilians. Alcohol and tobacco consumption may contribute to synchronous or metachronous head and neck cancer and esophageal cancer. A prospective study involving 60 patients with head and neck cancer was carried out at the State University of Campinas--UNICAMP, Campinas, SP, Brazil to screen for superficial esophageal cancer and dysplasia using endoscopy and a 2% lugol dye solution followed by biopsy of the suspicious areas. Five patients (8.3%) had superficial esophageal cancer, which was diagnosed as intraepithelial carcinoma in three of them (5.0%). In four patients, the superficial esophageal cancer was synchronous and in one it was metachronous to head and neck cancer. Five patients (8.3%) had dysplasias in the esophageal epithelium (three were classified as mild and two as moderate). These results demonstrate the value of endoscopic screening of the esophagus using lugol dye in patients with head and neck cancer, particularly since superficial esophageal cancer is extremely difficult to detect by conventional methods in asymptomatic patients.

  14. Morphologic changes in basal cells during repair of tracheal epithelium.

    PubMed Central

    Wang, C. Z.; Evans, M. J.; Cox, R. A.; Burke, A. S.; Zhu, Q.; Herndon, D. N.; Barrow, R. E.

    1992-01-01

    Basal cells are differentiated with respect to junctional adhesion mechanisms and play a role in attachment of columnar epithelium to the basal lamina. Although much is known about nonciliated and ciliated cell differentiation during the repair process after injury, little is known about the basal cell. We studied the morphology of basal cells and quantitated junctional adhesion structures during repair of tracheal epithelium exposed to toxic cotton smoke. Ten adult ewes were given a smoke injury to a portion of the upper cervical trachea and were killed at 4, 6, 8, 10, and 18 days after injury for morphometric studies. At 4 days, there was a stratified reparative epithelium over the basal lamina, which was two to four cells in depth. The basal cells were identified by their hemidesmosome (HD) attachment to the basal lamina. Basal cells were about 69% larger than controls and flattened rather than columnar. The amount of HD attachment was 192% greater than controls. In contrast, volume density of cytokeratin filaments had decreased about 47%. Basal cells had returned to normal numbers and size and a columnar shape by day 18. The amount of desmosome (D) and HD attachment and volume density of cytokeratins had also reached control levels by day 18. These data indicate that morphology of basal cells changes during the initial stages of reparative regeneration but returns to normal by 18 days. Morphologic changes appear to reflect changes in size of the cell associated with cell division rather than differentiation of recently divided basal cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1381564

  15. Expression of keratins in mouse vaginal epithelium.

    PubMed

    Gimenez-Conti, I B; Lynch, M; Roop, D; Bhowmik, S; Majeski, P; Conti, C J

    1994-05-01

    In the epithelium of the rodent vagina proliferation and differentiation are tightly regulated by ovarian hormones. Estrogens stimulate proliferation and squamous differentiation, whereas progesterone redirects differentiation to a mucus-secreting epithelium formed by goblet-like cells. In the present study, we used monospecific keratin antibodies to show the expression and distribution of keratins in SENCAR mouse vaginal epithelium in different stages of the estral cycle and in ovariectomized animals. In ovariectomized animals, the vaginal epithelium expressed K6, K8, K13 and K14, but not K1. After estrogen treatment, K1 was expressed. During proestrus and estrus, the keratin pattern was essentially identical to that observed in 17 beta-estradiol-stimulated animals. In contrast, during the progestational stages (metaestrus and diestrus) or after progesterone treatment of ovariectomized mice, the most relevant change was the loss of K1. Together, these results show that K1 expression is induced by estrogens in the vaginal epithelium. In contrast, K6, K8, K13 and K14 are constitutively expressed even when squamous differentiation is not observed.

  16. Olfactory epithelium changes in germfree mice

    PubMed Central

    François, Adrien; Grebert, Denise; Rhimi, Moez; Mariadassou, Mahendra; Naudon, Laurent; Rabot, Sylvie; Meunier, Nicolas

    2016-01-01

    Intestinal epithelium development is dramatically impaired in germfree rodents, but the consequences of the absence of microbiota have been overlooked in other epithelia. In the present study, we present the first description of the bacterial communities associated with the olfactory epithelium and explored differences in olfactory epithelium characteristics between germfree and conventional, specific pathogen-free, mice. While the anatomy of the olfactory epithelium was not significantly different, we observed a thinner olfactory cilia layer along with a decreased cellular turn-over in germfree mice. Using electro-olfactogram, we recorded the responses of olfactory sensitive neuronal populations to various odorant stimulations. We observed a global increase in the amplitude of responses to odorants in germfree mice as well as altered responses kinetics. These changes were associated with a decreased transcription of most olfactory transduction actors and of olfactory xenobiotic metabolising enzymes. Overall, we present here the first evidence that the microbiota modulates the physiology of olfactory epithelium. As olfaction is a major sensory modality for most animal species, the microbiota may have an important impact on animal physiology and behaviour through olfaction alteration. PMID:27089944

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

    PubMed

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

    2007-05-01

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

  18. Pradaxa-induced esophageal ulcer.

    PubMed

    Wood, Michele; Shaw, Paul

    2015-10-09

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

  19. Allergic Mechanisms in Eosinophilic Esophagitis

    PubMed Central

    Wechsler, Joshua B; Bryce, Paul J

    2014-01-01

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

  20. Acute Esophageal Necrosis: An Update

    PubMed Central

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

    2016-01-01

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

  1. Acute Esophageal Necrosis: An Update.

    PubMed

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

    2016-07-01

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

  2. Pharmacologic influence on esophageal varices

    SciTech Connect

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

    1983-06-01

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

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

    PubMed Central

    van Hoeij, Froukje B; Bredenoord, Albert J

    2016-01-01

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

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

    ClinicalTrials.gov

    2016-01-11

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

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

    PubMed

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

    2016-05-01

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

  6. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  7. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  8. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  9. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  10. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  11. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  12. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  13. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  14. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  15. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Esophageal prosthesis. 878.3610 Section 878.3610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices § 878.3610 Esophageal...

  16. Esophageal Impedance Monitoring: Clinical Pearls and Pitfalls.

    PubMed

    Ravi, Karthik; Katzka, David A

    2016-09-01

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

  17. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  18. Esophageal Impedance Monitoring: Clinical Pearls and Pitfalls.

    PubMed

    Ravi, Karthik; Katzka, David A

    2016-09-01

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

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

    SciTech Connect

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

    2015-09-11

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

  20. Effects of vocal fold epithelium removal on vibration in an excised human larynx model.

    PubMed

    Tse, Justin R; Zhang, Zhaoyan; Long, Jennifer L

    2015-07-01

    This study investigated the impact of selective epithelial injury on phonation in an excised human larynx apparatus. With intact epithelium, the vocal folds exhibited a symmetrical vibration pattern with complete glottal closure during vibration. The epithelium was then enzymatically removed from one, then both vocal folds, which led to left-right asymmetric vibration and a decreased closed quotient. Although the mechanisms underlying these vibratory changes are unclear, these results demonstrate that some component of an intact surface layer may play an important role in achieving normal symmetric vibration and glottal closure.

  1. Unusual Presentation of a Metastatic Esophageal Carcinoma

    PubMed Central

    Orlicka, Katarzyna; Maynard, Stéphanie; Bouin, Mickael

    2012-01-01

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

  2. [Esophageal papilloma: case report, molecular identification of human papillomavirus and literature review].

    PubMed

    Barbaglia, Yanina; Jiménez, Félix; Tedeschi, Fabián; Zalazar, Fabián

    2013-09-01

    sophageal squamous papilloma is an uncommon, usually asymptomatic, benign tumor of the squamous epithelium consisting of a raised, sessile, small and round (smooth or rough) lesion. The prevalence is between 0.01 and 0.45% of cases, with a male/female ratio of 3:1. The etiology and pathogenesis appear to be a mechanical or chemical irritation of the mucosa in addition to the presence of human papillomavirus (HPV), important agent in the evolution to a squamous carcinoma, especially HPV types 16 and 18. In this paper, we describe a case of esophageal papilloma whose diagnosis involved endoscopic images, pathological studies and detection of viral DNA by polymerase chain reaction. By using molecular techniques (PCR-RFLP) a profile consistent with HPV type 16 has been obtained. The patient underwent polypectomy and currently, after 3 years of diagnosis, he remains asymptomatic. This work is one of the first national reports of a patient with esophageal papilloma in which one of the most frequently HPV genotypes associated with esophageal carcinoma (HPV 16) has been detected.

  3. Esophageal desalination of seawater in flounder: role of active sodium transport.

    PubMed

    Parmelee, J T; Renfro, J L

    1983-12-01

    The esophagus of the flounder, Pseudopleuronectes americanus, was studied to determine how salinity of ingested seawater (SW) is decreased before fluid absorption in the intestine. Drinking rate was 2.5 ml X h-1 X kg-1. Stomach fluid osmolality was 45% that of seawater, and intestinal fluid was isosmotic to plasma. Esophagus and stomach were nearly impermeable to 28Mg; thus Mg concentrations were accurate indicators of fluid addition and NaCl removal between pharynx and stomach. Measurements of water and ion fluxes across isolated esophageal epithelium mounted in Ussing chambers and bathed by Ringer solution showed that the tritiated water flux was lower in esophagus than in intestine and that 22Na flux ratio was 1.4 (Jm leads to s/Js leads to m) regardless of acclimation medium (100 or 10% SW). Potential difference was zero, and electrical resistance averaged 90 omega X cm2. Mucosal-to-serosal Na transport was inhibited by 0.1 mM amiloride, 0.1 mM ouabain, and Cl-free medium, whereas 1.0 mM furosemide had no effect. Net esophageal Na absorption (mucosal-to-serosal) averaged 10.0 mumol X h-1 X cm-2 with mucosa exposed to SW and was inhibited 46% by 0.1 mM ouabain. Taken together the above observations suggest a role for both passive and active esophageal Na transport in SW desalination.

  4. Overexpression of Csk-binding protein decreases growth, invasion, and migration of esophageal carcinoma cells by controlling Src activation

    PubMed Central

    Zhou, Dong; Dong, Peng; Li, Yu-Min; Guo, Fa-Cai; Zhang, An-Ping; Song, Run-Ze; Zhang, Ya-Min; Li, Zhi-Yong; Yuan, Dong; Yang, Chuan

    2015-01-01

    AIM: To investigate the mechanisms by which Csk-binding protein (CBP) inhibits tumor progression in esophageal carcinoma. METHODS: A CBP overexpressing esophageal carcinoma cell line (TE-1) was established. The growth, invasion, and migration of CBP-TE-1 cells, as well as the expression of Src were then determined and compared with those in normal TE-1 cells. RESULTS: The expression of Src was decreased by the overexpression of CBP in TE-1 cells. The growth, invasion, and migration of TE-1 cells were decreased by the overexpression of CBP. CONCLUSION: This study indicates that CBP may decrease the metastasis of esophageal carcinoma by inhibiting the activation of Src. CBP may be a potential tumor suppressor and targeting the CBP gene may be an alternative strategy for the development of therapies for esophageal carcinoma. PMID:25684946

  5. GPR84 and TREM-1 Signaling Contribute to the Pathogenesis of Reflux Esophagitis

    PubMed Central

    Abdel-Aziz, Heba; Schneider, Mathias; Neuhuber, Winfried; Kassem, Abdel Meguid; Khailah, Saleem; Müller, Jürgen; Eldeen, Hadeel Gamal; Khairy, Ahmed; Khayyal, Mohamed T; Shcherbakova, Anastasiia; Efferth, Thomas; Ulrich-Merzenich, Gudrun

    2015-01-01

    Gastro-esophageal reflux disease (GERD) is one of the most common disorders in gastroenterology. Patients present with or without increased acid exposure indicating a nonuniform etiology. Thus, the common treatment with proton pump inhibitors (PPIs) fails to control symptoms in up to 40% of patients. To further elucidate the pathophysiology of the condition and explore new treatment targets, transcriptomics, proteomics and histological methods were applied to a surgically induced subchronic reflux esophagitis model in Wistar rats after treatment with either omeprazole (PPI) or STW5, a herbal preparation shown to ameliorate esophagitis without affecting refluxate pH. The normal human esophageal squamous cell line HET-1A and human endoscopic biopsies were used to confirm our findings to the G-protein–coupled receptor (GPR) 84 in human tissue. Both treatments reduced reflux-induced macroscopic and microscopic lesions of the esophagi as well as known proinflammatory cytokines. Proteomic and transcriptomic analyses identified CINC1–3, MIP-1/3α, MIG, RANTES and interleukin (IL)-1β as prominent mediators in GERD. Most regulated cyto-/chemokines are linked to the TREM-1 signaling pathway. The fatty acid receptor GPR84 was upregulated in esophagitis but significantly decreased in treated groups, a finding supported by Western blot and immunohistochemistry in both rat tissue and HET-1A cells. GPR84 was also found to be significantly upregulated in patients with grade B reflux esophagitis. The expression of GPR84 in esophageal tissue and its potential involvement in GERD are reported for the first time. IL-8 (CINC1–3) and the TREM-1 signaling pathway are proposed, besides GPR84, to play an important role in the pathogenesis of GERD.org PMID:26650186

  6. Leg raise increases pressure in lower and upper esophageal sphincter among patients with gastroesophageal reflux disease.

    PubMed

    Bitnar, P; Stovicek, J; Andel, R; Arlt, J; Arltova, M; Smejkal, M; Kolar, P; Kobesova, A

    2016-07-01

    The purpose of this study was to determine the relation between posturally increased intra-abdominal pressure and lower/upper esophageal sphincter pressure changes in patients with gastroesophageal reflux disease. We used high resolution manometry to measure pressure changes in lower and upper esophageal sphincter during bilateral leg rise. We also examined whether the rate of lower and upper esophageal sphincter pressure would increase during leg raise differentially in individuals with versus without normal resting pressure. Fifty eight patients with gastroesophageal reflux disease participated in the study. High resolution manometry was performed in relaxed supine position, then lower and upper esophageal sphincter pressure was measured. Finally, the subjects were instructed to keep their legs lifted while performing 90-degree flexion at the hips and knees and the pressure was measured again. Paired t-test and independent samples t-test were used. There was a significant increase in both lower (P < 0.001) and upper esophageal sphincter pressure (P = 0.034) during leg raise compared to the initial resting position. Individuals with initially higher pressure in lower esophageal sphincter (>10 mmHg) exhibited a greater pressure increase during leg raise than those with initially lower pressure (pressure ≤10 mmHg; P = 0.002). Similarly individuals with higher resting upper esophageal sphincter pressure (>44 mmHg) showed a greater pressure increase during leg raise than those with lower resting pressure (≤44 mmHg; P < 0.001). The results illustrate the influence of postural leg activities on intraesophageal pressure in patients with gastroesophageal reflux disease, indicating by means of high resolution manometry that diaphragmatic postural and sphincter function are likely interrelated in this population. PMID:27634073

  7. Leg raise increases pressure in lower and upper esophageal sphincter among patients with gastroesophageal reflux disease.

    PubMed

    Bitnar, P; Stovicek, J; Andel, R; Arlt, J; Arltova, M; Smejkal, M; Kolar, P; Kobesova, A

    2016-07-01

    The purpose of this study was to determine the relation between posturally increased intra-abdominal pressure and lower/upper esophageal sphincter pressure changes in patients with gastroesophageal reflux disease. We used high resolution manometry to measure pressure changes in lower and upper esophageal sphincter during bilateral leg rise. We also examined whether the rate of lower and upper esophageal sphincter pressure would increase during leg raise differentially in individuals with versus without normal resting pressure. Fifty eight patients with gastroesophageal reflux disease participated in the study. High resolution manometry was performed in relaxed supine position, then lower and upper esophageal sphincter pressure was measured. Finally, the subjects were instructed to keep their legs lifted while performing 90-degree flexion at the hips and knees and the pressure was measured again. Paired t-test and independent samples t-test were used. There was a significant increase in both lower (P < 0.001) and upper esophageal sphincter pressure (P = 0.034) during leg raise compared to the initial resting position. Individuals with initially higher pressure in lower esophageal sphincter (>10 mmHg) exhibited a greater pressure increase during leg raise than those with initially lower pressure (pressure ≤10 mmHg; P = 0.002). Similarly individuals with higher resting upper esophageal sphincter pressure (>44 mmHg) showed a greater pressure increase during leg raise than those with lower resting pressure (≤44 mmHg; P < 0.001). The results illustrate the influence of postural leg activities on intraesophageal pressure in patients with gastroesophageal reflux disease, indicating by means of high resolution manometry that diaphragmatic postural and sphincter function are likely interrelated in this population.

  8. In vitro reconstruction of human junctional and sulcular epithelium

    PubMed Central

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

    2013-01-01

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

  9. Connexins form functional hemichannels in porcine ciliary epithelium

    PubMed Central

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

    The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduced into the aqueous humor compartment for 30 min, fluorescence microscopy revealed PI in the NPE cell layer. PI entry into the NPE was inhibited by calcium and by the connexin antagonist 18α-glycyrrhetinic acid (18-AGA). Studies also were carried out with cultured porcine NPE. Under normal conditions, little PI entered the cultured cells but calcium-free medium stimulated PI accumulation and the entry was inhibited by 18-AGA. In cells loaded with calcein (MW 622), calcium-free solution stimulated calcein exit. 18-AGA partially suppressed calcein exit in calcium-free medium. Connexin 43 and connexin 50 proteins were detected by western blot analysis in both native and cultured NPE. In the intact eye, immunolocalization studies revealed connexin 50 at the basolateral, aqueous humor-facing, margin of the NPE. In contrast, connexin 43 was observed at the junction of the PE and NPE layer and on the basolateral membrane of PE. The results point to functional hemichannels at the NPE basolateral surface. It is feasible that hemichannels might contribute to the transfer of substances between the ciliary epithelium cytoplasm and aqueous humor. PMID:24262135

  10. Connexins form functional hemichannels in porcine ciliary epithelium.

    PubMed

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

    The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduced into the aqueous humor compartment for 30 min, fluorescence microscopy revealed PI in the NPE cell layer. PI entry into the NPE was inhibited by calcium and by the connexin antagonist 18α-glycyrrhetinic acid (18-AGA). Studies also were carried out with cultured porcine NPE. Under normal conditions, little PI entered the cultured cells but calcium-free medium stimulated PI accumulation and the entry was inhibited by 18-AGA. In cells loaded with calcein (MW 622), calcium-free solution stimulated calcein exit. 18-AGA partially suppressed calcein exit in calcium-free medium. Connexin 43 and connexin 50 proteins were detected by western blot analysis in both native and cultured NPE. In the intact eye, immunolocalization studies revealed connexin 50 at the basolateral, aqueous humor-facing, margin of the NPE. In contrast, connexin 43 was observed at the junction of the PE and NPE layer and on the basolateral membrane of PE. The results point to functional hemichannels at the NPE basolateral surface. It is feasible that hemichannels might contribute to the transfer of substances between the ciliary epithelium cytoplasm and aqueous humor.

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

    SciTech Connect

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

    2010-05-14

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

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-02-01

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

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

    SciTech Connect

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

    2012-01-01

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

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

    PubMed

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

    2009-01-01

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

  16. Differential Expression Patterns of EGF, EGFR, and ERBB4 in Nasal Polyp Epithelium

    PubMed Central

    Zhao, Li; Subramaniam, Somasundaram; Yu, Xue Min; Li, Ying Ying; Chen, De Hua; Li, Tian Ying; Shen, Liang; Shi, Li; Wang, De Yun

    2016-01-01

    Epidermal growth factor receptors play an important role in airway epithelial cell growth and differentiation. The current study investigates the expression profiles of EGF, EGFR and ERBB4 in patients with nasal polyps (NP), and their response to glucocorticosteroid (GC) treatment. Fifty patients with NP (40 without GC treatment and 10 with oral GC) and 20 control subjects with septal deviation were recruited into the study. Protein levels of EGF, EGFR, and ERBB4 were evaluated by immune-staining. In healthy nasal epithelium, EGF and EGFR localized within p63+ basal cells, while ERBB4 localized within ciliated cells. GC-naïve NP epithelium showed weak expression of EGF in 90% of samples versus 5% of controls. EGFR was significantly increased in the epithelium with basal cell hyperplasia from GC-naïve NPs (78%, 31/40) compared to controls (23%, 4/17). EGFR was also found in some degranulating goblet cells. ERBB4 expression was significantly higher in hyperplastic epithelium from GC-naïve NPs (65%, 26/40) than in controls (6%, 1/17). GC treatment restored the EGF expression and normalized the EGFR and ERBB4 expression in NPs. Differential expression patterns of EGF, EGFR, and ERBB4 are essential in epithelial restitution and remodeling in nasal epithelium. PMID:27285994

  17. Surface-enhanced Raman spectra of hemoglobin for esophageal cancer diagnosis

    NASA Astrophysics Data System (ADS)

    Zhou, Xue; Diao, Zhenqi; Fan, Chunzhen; Guo, Huiqiang; Xiong, Yang; Tang, Weiyue

    2014-03-01

    Surface-enhanced Raman scattering (SERS) spectra of hemoglobin from 30 esophageal cancer patients and 30 healthy persons have been detected and analyzed. The results indicate that, there are more iron ions in low spin state and less in high for the hemoglobin of esophageal cancer patients than normal persons, which is consistent with the fact that it is easier to hemolyze for the blood of cancer patients. By using principal component analysis (PCA) and discriminate analysis, we can get a three-dimensional scatter plot of PC scores from the SERS spectra of healthy persons and cancer patients, from which the two groups can be discriminated. The total accuracy of this method is 90%, while the diagnostic specificity is 93.3% and sensitivity is 86.7%. Thus SERS spectra of hemoglobin analysis combined with PCA may be a new technique for the early diagnose of esophageal cancer.

  18. A report of three cases of surgical removal of esophageal schwannomas.

    PubMed

    Chen, Xiankai; Li, Yin; Liu, Xianben; Fu, Huaiping; Sun, Haibo; Zhang, Ruixiang; Wang, Zongfei; Zheng, Yan

    2016-05-01

    Esophageal schwannomas are rarely observed, and the most frequent presenting symptom is dysphagia. In such cases, esophageal endoscopy shows a mucosal protrusion with normal esophageal mucosa. Esophagography shows a protruding smooth mass in the middle thoracic esophagus. Both fluorodeoxyglucose (FDG) positron emission tomography (PET) and endoscopic ultrasonography-fine needle aspiration (EUS-FNA) are limited for diagnosing the case. Diagnosis of this condition before surgery is difficult. The most common and effective treatment is enucleation through surgery or endoscopy. Thoracoscopic surgery is gradually becoming used more often, and the prognosis is particularly good. In comparison, thoracoscopy surgery is less invasive, with a shorter length of hospital stay, and reduced pain at the surgical wound site. Extended lymph node dissection was not performed. The positive expression of S-100 on immunohistochemistry examination indicates the nature of the schwannoma. In the present cases, the postoperative course was uneventful, and no evidence of recurrence has been noted. PMID:27162699

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

    PubMed Central

    Lin, Steven H.

    2011-01-01

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

  20. Effect of Perilla frutescens Fixed Oil on Experimental Esophagitis in Albino Wistar Rats

    PubMed Central

    Arya, Ekta; Saha, Sudipta; Saraf, Shubhini A.; Kaithwas, Gaurav

    2013-01-01

    The present study was undertaken to elucidate the effect of Perilla frutescens fixed oil on experimental esophagitis in albino rats. A group of rats (n = 6), treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.) and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or pantoprazole (30 mg/kg, i.p.), were subjected to pylorus and forestomach ligation. Animals were sacrificed after 6 h and evaluated for the gastric pH, volume of gastric juices, total acidity, esophagitis index and free acidity. Esophageal tissues were further subjected to estimations of TBARS, GSH, catalase, and SOD. Treatment with fixed oil significantly inhibited the gastric secretion, total acidity, and esophagitis index. The oil also helped to restore the altered levels of oxidative stress parameters to normal. The present study also makes evident the in vitro antihistaminic and anticholinergic activity of alpha linolenic acid (ALA) (18 : 3, n − 3) on isolated rat ileum preparation. The lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic), and antioxidant activity of the oil was attributed for its efficacy in reflux esophagitis. PMID:24027769

  1. Fruit Consumption Reduces the Risk of Esophageal Cancer in Yanting, People's Republic of China.

    PubMed

    Song, Qingkun; Zhao, Lin; Li, Jun; Ren, Jun

    2015-05-01

    This study aimed to investigate the contribution of fruit and family history to esophageal cancer, among residents with abnormal esophagus discovered in screening. The study was a frequency-matched case-control design in groups of normal esophagus, abnormal esophagus but not carcinoma, and esophageal squamous cell carcinoma. Odds ratio (OR) was estimated by unconditional logistic regression. Fruit intake (OR = 0.19, 95% CI = 0.06-0.56) and positive family history of esophageal cancer (OR = 3.87, 95% CI = 1.41-10.63) were associated with esophageal cancer compared to individuals with abnormal conditions of the esophagus. In individuals who consumed fruits at least once per week, the OR for family cancer history is reduced to a nonsignificant level (OR = 1.06, 95% CI = 0.07-15.91). In the individuals with abnormal esophagus at screening, fruit intake was possibly protective against esophageal cancer, even in the ones with positive family history. Local public health strategies should focus on the improvement in fruit intake.

  2. Enzymatic digestion of esophageal meat impaction. A study of Adolph's Meat Tenderizer.

    PubMed

    Goldner, F; Danley, D

    1985-05-01

    While a solution of Adolph's Meat Tenderizer (AMT) is commonly used to treat esophageal meat impaction, few studies describe its clinical effects. We examined AMT with regard to (1) its papain activity; (2) its ability to digest meat cubes in vitro; and (3) its effect on rabbit esophageal mucosa. A standard papain assay was developed against which the activity of AMT was compared. Proteolytic activity was detected in AMT only when the papain activators, 0.02 M cysteine and 0.008 M EDTA, were added to the system. Meat cubes incubated in AMT solution exhibited no evidence of digestion as determined by protein release or change in sample weight. A solution of AMT had no adverse effect on normal esophageal mucosa in rabbits, but significantly increased esophagitis when infused onto previously inflamed mucosa. We conclude that AMT solution has no inherent capacity to digest or to reduce the size of an impacted meat bolus, and may, in fact, worsen existing esophagitis. PMID:3921329

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

    PubMed

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

    2015-06-01

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

  4. Mechanisms of Acid and Base Secretion by the Airway Epithelium

    PubMed Central

    Fischer, Horst; Widdicombe, Jonathan H.

    2010-01-01

    SUMMARY One of the main functions of the airway epithelium is to inactivate and remove infectious particles from inhaled air and thereby prevent infection of the distal lung. This function is achieved by mucociliary and cough clearance and by antimicrobial factors present in the airway surface liquid (ASL). There are indications that airway defenses are affected by the pH of the ASL and historically, acidification of the airway surfaces has been suggested as a measure of airway disease. However, even in health, the ASL is slightly acidic, and this acidity might be part of normal airway defense. Only recently research has focused on the mechanisms responsible for acid and base secretion into the ASL. Advances resulted from research into the airway disease associated with cystic fibrosis (CF) after it was found that the CFTR C1- channel conducts HCO3- and, therefore, may contribute to ASL pH. However, the acidity of the ASL indicated parallel mechanisms for H+ secretion. Recent investigations identified several H+ transporters in the apical membrane of the airway epithelium. These include H+ channels and ATP-driven H+ pumps, including a non-gastric isoform of the H+-K+ ATPase and a vacuolar-type H+ ATPase. Current knowledge of acid and base transporters and their potential roles in airway mucosal pH regulation is reviewed here. PMID:17091214

  5. An Apical-Membrane Chloride Channel in Human Tracheal Epithelium

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.

    1986-06-01

    The mechanism of chloride transport by airway epithelia has been of substantial interest because airway and sweat gland-duct epithelia are chloride-impermeable in cystic fibrosis. The decreased chloride permeability prevents normal secretion by the airway epithelium, thereby interfering with mucociliary clearance and contributing to the morbidity and mortality of the disease. Because chloride secretion depends on and is regulated by chloride conductance in the apical cell membrane, the patch-clamp technique was used to directly examine single-channel currents in primary cultures of human tracheal epithelium. The cells contained an anion-selective channel that was not strongly voltage-gated or regulated by calcium in cell-free patches. The channel was also blocked by analogs of carboxylic acid that decrease apical chloride conductance in intact epithelia. When attached to the cell, the channel was activated by isoproterenol, although the channel was also observed to open spontaneously. However, in some cases, the channel was only observed after the patch was excised from the cell. These results suggest that this channel is responsible for the apical chloride conductance in airway epithelia.

  6. Effect of esophageal emptying and saliva on clearance of acid from the esophagus

    SciTech Connect

    Helm, J.F.; Dodds, W.J.; Pelc, L.R.; Palmer, D.W.; Hogan, W.J.; Teeter, B.C.

    1984-02-02

    The clearance of acid from the esophagus and esophageal emptying in normal subjects was studied. A 15-ml bolus of 0.1 N hydrochloric acid (pH 1.2) radiolabeled with (/sup -99m/Tc)sulfur colloid was injected into the esophagus, and the subject swallowed every 30 seconds. Concurrent manometry and radionuclide imaging showed nearly complete emptying of acid from the esophagus by an immediate secondary peristaltic sequence, although esophageal pH did not rise until the first swallow 30 seconds later. Esophageal pH then returned to normal by a series of step increases, each associated with a swallow-induced peristaltic sequence. Saliva stimulation by an oral lozenge shortened the time required for acid clearance, whereas aspiration of saliva from the mouth abolished acid clearance. Saliva stimulation or aspiration did not affect the virtually complete emptying of acid volume by the initial peristaltic sequence. It was concluded that esophageal acid clearance normally occurs as a two-step process: (1) virtually all acid volume is emptied from the esophagus by one or two peristaltic sequences, leaving a minimal residual amount that sustains a low pH, and (2) residual acid is neutralized by swallowed saliva. 13 references, 3 figures.

  7. Effect of esophageal emptying and saliva on clearance of acid from the esophagus

    SciTech Connect

    Helm, J.F.; Dodds, W.J.; Pelc, L.R.; Palmer, D.W.; Hogan, W.J.; Teeter, B.C.

    1984-02-02

    The clearance of acid from the esophagus and esophageal emptying in normal subjects was studied. A 15-ml bolus of 0.1 N hydrochloric acid (pH 1.2) radiolabeled with (/sup 99m/Tc)sulfur colloid was injected into the esophagus, and the subject swallowed every 30 seconds. Concurrent manometry and radionuclide imaging showed nearly complete emptying of acid from the esophagus by an immediate secondary peristaltic sequence, although esophageal pH did not rise until the first swallow 30 seconds later. Esophageal pH then returned to normal by a series of step increases, each associated with a swallow-induced peristaltic sequence. Saliva stimulation by an oral lozenge shortened the time required for acid clearance, whereas aspiration of saliva from the mouth abolished acid clearance. Saliva stimulation or aspiration did not affect the virtually complete emptying of acid volume by the initial peristaltic sequence. It was concluded that esophageal acid clearance normally occurs as a two-step process: (1) Virtually all acid volume is emptied from the esophagus by one or two peristaltic sequences, leaving a minimal residual amount that sustains a low pH, and (2) residual acid is neutralized by swallowed saliva.

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

    PubMed Central

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

    2015-01-01

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

  9. Role of advanced diagnostics for eosinophilic esophagitis.

    PubMed

    Hirano, Ikuo

    2014-01-01

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

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

    SciTech Connect

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

    2007-10-01

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

  11. High resolution integrative analysis reveals widespread genetic and epigenetic changes after chronic in-vitro acid and bile exposure in Barrett's epithelium cells.

    PubMed

    Bajpai, Manisha; Kessel, Rachel; Bhagat, Tushar; Nischal, Sangeeta; Yu, Yiting; Verma, Amit; Das, Kiron M

    2013-12-01

    Barrett's epithelium (BE) is a premalignant condition resulting from chronic gastroesophageal reflux that may progress to esophageal adenocarcinoma (EAC). Early intervention holds promise in preventing BE progression. However, identification of high-risk BE patients remains challenging due to inadequate biomarkers for early diagnosis. We investigated the effect of prolonged chronic acid and bile exposure on transcriptome, methylome, and mutatome of cells in an in-vitro BE carcinogenesis (BEC) model. Twenty weeks acid and bile exposed cells from the BEC model (BEC20w) were compared with their naïve predecessors HiSeq Illumina based RNA sequencing was performed on RNA from both the cells for gene expression and mutational analysis. HELP Tagging Assay was performed for DNA methylation analysis. Ingenuity pathway, Gene Ontology, and KEGG PATHWAY analyses were then performed on datasets. Widespread aberrant genetic and epigenetic changes were observed in the BEC20w cells. Combinatorial analyses revealed 433 from a total of 863 downregulated genes had accompanying hypermethylation of promoters. Simultaneously, 690 genes from a total of 1,492 were upregulated with accompanying promoter hypomethylation. In addition, 763 mutations were identified on 637 genes. Ingenuity pathway analysis, Gene Ontology, and KEGG PATHWAY analyses associated the genetic and epigenetic changes in BEC20w cells with cellular and biological functions. Integration of high resolution comparative analyses of naïve BAR-T and BEC20w cells revealed striking genetic and epigenetic changes induced by chronic acid and bile exposure that may disrupt normal cellular functions and promote carcinogenesis. This novel study reveals several potential targets for future biomarkers and therapeutic development.

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

    PubMed

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

    2012-06-01

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

  13. Updates on esophageal and gastric cancers

    PubMed Central

    Gallo, Amy; Cha, Charles

    2006-01-01

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

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

    PubMed Central

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

    2016-01-01

    Iatrogenic esophageal perforation (IEP) is a potentially serious adverse event of interventional endoscopy. The approach to IEP varies from surgical repair for large perforations to conservative treatment for small contained perforations. We report a case of an 18-month-old girl with congenital esophageal stenosis suffering a large esophageal perforation after a trial of stricture dilatation, which was successfully managed by the placement of fully covered stent. Hence, in selected cases, esophageal stent placement is a feasible alternative to invasive surgery in managing IEP. PMID:27144142

  15. [Laparoscopic surgery for esophageal achalasia].

    PubMed

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

    2000-04-01

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

  16. Ingested acidic food and liquids may lead to misinterpretation of 24-hour ambulatory pH tests: focus on measurement of extra-esophageal reflux.

    PubMed

    Koskenvuo, Juha W; Pärkkä, Jussi P; Hartiala, Jaakko J; Kinnunen, Ilpo; Peltola, Matti; Sala, Eeva

    2007-07-01

    Normal values of extra-esophageal reflux are difficult to determine owing to variation in the location of the proximal electrode, limited information on the ingestion of acidic food, different exclusion periods for meals, and poor reproducibility of measurement of extra-esophageal reflux. We studied whether ambulatory esophageal pH testing is disturbed by acidic food ingestion. Eighteen healthy subjects were enrolled in standard dual-channel esophageal pH tests (recorder 1). Ten subjects were equipped with another pH device (recorder 2), positioned to measure extra-esophageal reflux. The subjects were exposed to controlled ingestion of different acidic food or liquid for five 1-min periods. The present study showed that acidic food ingestion for 5 min has a significant effect on the outcome of standard dual-channel ambulatory pH testing. Reflux occurs equally on proximal channels during ingestion of acidic food, whether the proximal channel position is normal or 2 cm above the upper esophageal sphincter. We recommend avoiding acidic food intake during esophageal pH testing.

  17. Esophageal and small intestinal manifestations of progressive systemic sclerosis. A clinical and experimental study.

    PubMed

    Hendel, L

    1994-09-01

    Progressive systemic sclerosis (PSS) is a systemic disease with a high frequency of gastro-intestinal involvement. The present thesis deals with the occurrence of, the complications to, and the treatment of the esophageal manifestations combined with more experimental studies on small intestine manifestations. The conclusions in this thesis are based on results achieved in 9 original previously published papers. The pattern of esophageal dysmotility is thoroughly evaluated in 156 consecutive PSS patients and is found to be identical to what is found in other large series of PSS patients. In paper no. I dysmotility variables are correlated to the occurrence of gastroesophageal reflux (GER) and it is shown that also in this group of patients with well defined dysmotility problems the only reliable GER test is pH-metry. Esophageal dysmotility furthers esophageal candidosis, which is further facilitated by anti-reflux treatment. This problem is evaluated in paper no. V. Progression of esophageal dysmotility in spite of D-penicillamine treatment is shown in paper no. VII and confirms the non-stable condition of the PSS patient in regard to esophageal manifestations and complications. This point is also outlined in paper no. IX concerning surveillance and continuous treatment of esophageal PSS. Esophageal stricturing is a well-known entity in PSS. The etiologic question of esophageal stricturing being a manifestation of PSS and/or a peptic complication, is approached in paper no. VIII. PSS manifestations of the small intestine are not as frequent as in the esophagus, in the present material only 19% presented with X-ray changes. However, bacterial count of duodenal juice as an indirect measurement of small intestinal dysmotility in paper no. VI indicates a much larger percentage of small intestinal involvement than revealed by X-ray. In paper no. VI the exocrine pancreatic function was assessed in 16 PSS patients. It is shown that the endogenous stimulation capacity is

  18. Palliative Treatment of Esophageal Cancer.

    PubMed

    Ahmad; Goosenberg; Frucht; Coia

    1994-07-01

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

  19. Mechanically patterning the embryonic airway epithelium

    PubMed Central

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

    2015-01-01

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

  20. Odors Discrimination by Olfactory Epithelium Biosensor

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

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

  1. Comparison of the effects of different menstrual tampons on the vaginal epithelium: a randomised clinical trial.

    PubMed

    Raudrant, D; Landrivon, G; Frappart, L; De Haas, P; Champion, F; Ecochard, R

    1995-01-01

    The effects on the vaginal epithelium of three different menstrual tampons in normal conditions of use were studied in 41 women during the menstrual period. The vaginal epithelium was studied in a total of 123 cycles at a structural and ultra-structural level with colposcopy, vaginal smear and biopsy on TEM and SEM. One of the three tampons studied showed a lower level of abnormalities on colposcopy (36.6% vs. 56.1% vs. 68.3%), with an inverse correlation between the severity of the dryness and the quantity of blood absorbed by the tampon (4.2 g when the colposcopy was normal vs. 1.8 g in case of severe dryness). Cytology is not a good test for assessing the effects of tampons because of the high rate of acellular and uninterpretable samplings. The biopsy effects were defined according to their depth in the epithelium. The same tampon showed the lowest level in biopsy abnormalities. No correlation was found between severity of the colposcopy and biopsy results. Colposcopy can demonstrate the degree of severity of dryness or any other effect, but biopsy only confirms the effect and does not correlate the degree of severity. Materials and designs of tampons can play a role in reducing the drying effects to the vaginal epithelium.

  2. X-ray microanalysis of hamster tracheal epithelium

    SciTech Connect

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

    1989-06-01

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

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

    PubMed Central

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

    2012-01-01

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

  4. Effect of Slip Time in Forming Neo-Esophageal Stenosis After Replacement of a Thoracic Esophagus With Nitinol Artificial Esophagus.

    PubMed

    Liang, Xian-Liang; Liang, Jian-Hui

    2015-07-01

    Attempts have been made to investigate the effect of slip time of nitinol artificial esophagus for forming neo-esophageal stenosis after replacement of a thoracic esophagus with nitinol artificial esophagus in 20 experimental pigs. The pigs whose slip time was less than 90 days postoperatively had severe dysphagia (Bown's III) immediately after they were fed, and the dysphagia aggravated gradually later on (Bown's III-IV). The pigs whose slip time was more than 90 days postoperatively had mild/moderate dysphagia (Bown's I-II) immediately after they were fed, and the dysphagia relieved gradually later on (Bown's II-I-0). The ratios between the diameter of neo-esophagus in different slip time and normal esophagus were 25% (at 2 months postoperatively), 58% (at 4 months postoperatively), and 93% (at 6 months postoperatively), respectively. The relationship between nitinol artificial esophagus slip time and neo-esophageal stenosis showed a positive correlation. After replacement of a thoracic esophagus with nitinol artificial esophagus, the artificial esophageal slip time not only affected the original diameter of the neo-esophagus immediately, but also affected the neo-esophageal scar stricture forming process later on. The narrowing of neo-esophagus is caused by overgrowth of scar tissue. But there is the positive correlation between artificial esophagus slip time and neo-esophageal stenosis, so this can be a way of overcoming neo-esophageal stenosis by delaying slip time of artificial esophagus.

  5. Development of the ovarian follicular epithelium.

    PubMed

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

    1999-05-25

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

  6. The role of lens epithelium in sugar cataract formation.

    PubMed

    Robison, W G; Houlder, N; Kinoshita, J H

    1990-06-01

    Previous evidence has shown clearly that sugar cataract formation results from unusually high intracellular levels of polyol. Documentation of polyol-related histological changes in the cortical fiber cells of the equatorial zone has been extensive. However, little attention has been given to the early changes in the lens epithelial cells, in spite of the fact that the highest level of aldose reductase is found in this layer of the lens. Also, cultured lens epithelial cells exposed to high sugar levels exhibit rapid accumulation of polyol and show ultrastructural alterations. Therefore, a study was designed to evaluate the role of the lens epithelium in sugar cataract formation. Specifically, an attempt was made to localize the earliest fine structural lesions in intact lenses of galactose-fed rats and to test their relation to aldose reductase. Rats were fed either a normal diet or a 50% galactose diet with or without sorbinil, an aldose reductase inhibitor. Rats were killed at varying periods of time ranging from 6 to 96 hr, and the eyes were processed for light and electron microscopy. The first detectable abnormalities occurred after 36 hr of galactose feeding, and were limited to the central lens epithelium. Cell edema, apparent dilution of cytoplasm, rounding of nuclei, aberrant intracellular vacuoles, and loss of normal tortuosity of cell boundaries were the salient lesions. No changes were detectable in the equatorial zone until 48 hr, and no deviation from the control structure was found in any of the rats treated with an aldose reductase inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Quantification of PCNA+ cells within odontogenic jaw cyst epithelium.

    PubMed

    Li, T J; Browne, R M; Matthews, J B

    1994-04-01

    The aim of this study was to investigate the reactivity of the epithelial linings of the three major types of odontogenic cyst with a monoclonal antibody to proliferating cell nuclear antigen (PCNA; clone PC10). PCNA expression was studied in odontogenic cysts (n = 31) and normal oral epithelium (n = 10) using a biotin-streptavidin method on routinely processed paraffin sections. PCNA+ cells were counted manually and related to the length of basement membrane (mm) and the epithelial area (mm2) as determined by TV image analysis. The epithelial linings of odontogenic keratocysts (OKC; n = 11) contained the highest number of PCNA+ cells, most of which were located in the suprabasal layers. The mean value of PCNA+ cells in OKC linings (94.4 +/- 22.7 cells/mm) was similar to that of oral epithelia (80.8 +/- 20.6 cells/mm), but both were significantly higher than that of dentigerous (n = 10, 5.1 +/- 3.0 cells/mm) and radicular (n = 10, 11.0 +/- 4.1 cells/mm) cyst linings (P < 0.005). The epithelial distribution of PCNA+ cells differed between groups with the basal/suprabasal PCNA+ cell ratio in OKC linings (0.05 +/- 0.02) being significantly lower than that of normal oral epithelium (0.5 +/- 0.14), dentigerous (1.6 +/- 1.23) and radicular (1.9 +/- 1.09) cyst linings respectively (P < 0.005). These results demonstrate differences in PCNA expression between the epithelial linings of the major odontogenic cyst types, indicating differences in proliferative and differentiation processes within these lesions.

  8. Functional subtyping of muscarinic receptors on canine esophageal mucosa.

    PubMed

    Lad, R; Donoff, B; Rangachari, P K

    1991-09-01

    Serosal addition of muscarinic agonists elicited rapid changes in electrical parameters across the isolated canine esophageal epithelium set up in vitro. Both carbachol and the M1-selective agonist, McNeil A343 (McN), increased transmucosal potential differences (PDs), decreased transmucosal resistances (R), and increased short-circuit currents (Isc). Carbachol was more potent and more effective than McN. Muscarinic antagonists were used to define the muscarinic receptor involved. The pA2 values obtained with Schild plots were as follows: atropine 9.14, 4-DAMP 8.98, AFDX-116 6.71, and pirenzepine 7.12. Low concentrations of pirenzepine (10(-8) M), produced a rightward shift in the dose-response curve to McN, without inhibiting responses to carbachol. Thus the receptor subtype is clearly not an M2. As in other glandular systems, M3 receptors are present. Whether M1 receptors also exist requires better definition of receptor densities-reserves in this tissue. Carbachol induced net secretion of Na and Cl and converted a predominantly absorptive tissue to a secretory one. PMID:1716057

  9. Managing eosinophilic esophagitis: challenges and solutions

    PubMed Central

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

    2016-01-01

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

  10. Regenerative Medicine Strategies for Esophageal Repair

    PubMed Central

    Londono, Ricardo

    2015-01-01

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

  11. Managing eosinophilic esophagitis: challenges and solutions

    PubMed Central

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

    2016-01-01

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

  12. Esophageal papilloma: Flexible endoscopic ablation by radiofrequency

    PubMed Central

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

    2015-01-01

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

  13. Alcohol, Obesity Could Raise Esophageal Cancer Risk

    MedlinePlus

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

  14. Multidisciplinary management for esophageal and gastric cancer.

    PubMed

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

    2016-01-01

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

  15. Multidisciplinary management for esophageal and gastric cancer

    PubMed Central

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

    2016-01-01

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

  16. Clinical application of endoscopic ultrasonography for esophageal achalasia.

    PubMed

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

    2015-04-01

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

  17. Novel organelles in primate retinal epithelium.

    PubMed

    Biesemeier, A; Gouras, P

    2016-10-01

    We are investigating age-related changes in organelles in monkey retinal epithelium using transmission and analytic electron microscopy. We previously described a circular organelle in retinal epithelium with a diameter of about 0.5μm. The organelle is unique in containing a single, round vacuole within an otherwise electron dense interior. We suggested that the organelle might be a melanosome with lysosomal properties. We now find that there are two similar organelles with such a single vacuole but which differ in their chemical composition, electron density, cell location and according to age. Epon embedded sections from the macular epithelium of seven monkeys, ranging from 1 to 35 years of age, were examined by transmission electron microscopy. A seven year old monkey was processed for analytic electron microscopy to determine the chemical composition of the organelles. The number and location of the organelles in the retinal epithelium were determined. The chemical composition of these two organelles was different. One of the organelles contained high mole fractions of oxygen and nitrogen and little phosphorous characteristic of melanin; the other had little oxygen and nitrogen and higher mole fractions of phosphorous uncharacteristic of melanin, but more common with lysosomal organelles. The latter had an electron dense rim around the vacuole, a less electron dense interior than the melanin containing organelle and also contained iron. The melanin containing organelle was more common in young monkeys and in the middle third of the cell. The organelle without melanin was more common in old monkeys and localized in the basal third of the cell. Two similarly vacuolated organelles, not identified before in retinal epithelium, differ in their chemical composition. One contains melanin; the other does not. The former is more common in young and the latter more common in old monkeys. This suggests reorganization and or degradation of melanin-containing organelles

  18. Novel organelles in primate retinal epithelium.

    PubMed

    Biesemeier, A; Gouras, P

    2016-10-01

    We are investigating age-related changes in organelles in monkey retinal epithelium using transmission and analytic electron microscopy. We previously described a circular organelle in retinal epithelium with a diameter of about 0.5μm. The organelle is unique in containing a single, round vacuole within an otherwise electron dense interior. We suggested that the organelle might be a melanosome with lysosomal properties. We now find that there are two similar organelles with such a single vacuole but which differ in their chemical composition, electron density, cell location and according to age. Epon embedded sections from the macular epithelium of seven monkeys, ranging from 1 to 35 years of age, were examined by transmission electron microscopy. A seven year old monkey was processed for analytic electron microscopy to determine the chemical composition of the organelles. The number and location of the organelles in the retinal epithelium were determined. The chemical composition of these two organelles was different. One of the organelles contained high mole fractions of oxygen and nitrogen and little phosphorous characteristic of melanin; the other had little oxygen and nitrogen and higher mole fractions of phosphorous uncharacteristic of melanin, but more common with lysosomal organelles. The latter had an electron dense rim around the vacuole, a less electron dense interior than the melanin containing organelle and also contained iron. The melanin containing organelle was more common in young monkeys and in the middle third of the cell. The organelle without melanin was more common in old monkeys and localized in the basal third of the cell. Two similarly vacuolated organelles, not identified before in retinal epithelium, differ in their chemical composition. One contains melanin; the other does not. The former is more common in young and the latter more common in old monkeys. This suggests reorganization and or degradation of melanin-containing organelles

  19. SU-C-BRA-04: Use of Esophageal Wall Thickness in Evaluation of the Response to Chemoradiation Therapy for Esophageal Cancer

    SciTech Connect

    Wang, J; Kligerman, S; Lu, W; Kang, M

    2015-06-15

    Purpose: To quantitatively evaluate the esophageal cancer response to chemoradiation therapy (CRT) by measuring the esophageal wall thickness in CT. Method: Two datasets were used in this study. The first dataset is composed of CT scans of 15 esophageal cancer patients and 15 normal controls. The second dataset is composed of 20 esophageal cancer patients who underwent PET/CT scans before (Pre-CRT) and after CRT (Post-CRT). We first segmented the esophagus using a multi-atlas-based algorithm. The esophageal wall thickness was then computed, on each slice, as the equivalent circle radius of the segmented esophagus excluding the lumen. To evaluate the changes of wall thickness, we computed the standard deviation (SD), coefficient of variation (COV, SD/Mean), and flatness [(Max–Min)/Mean] of wall thickness along the entire esophagus. Results: For the first dataset, the mean wall thickness of cancer patients and normal controls were 6.35 mm and 6.03 mm, respectively. The mean SD, COV, and flatness of the wall thickness were 2.59, 0.21, and 1.27 for the cancer patients and 1.99, 0.16, and 1.13 for normal controls. Statistically significant differences (p < 0.05) were identified in SD and flatness. For the second dataset, the mean wall thickness of pre-CRT and post-CRT patients was 7.13 mm and 6.84 mm, respectively. The mean SD, COV, and flatness were 1.81, 0.26, and 1.06 for pre-CRT and 1.69, 0.26, and 1.06 for post-CRT. Statistically significant difference was not identified for these measurements. Current results are based on the entire esophagus. We believe significant differences between pre- and post-CRT scans could be obtained, if we conduct the measurements at tumor sites. Conclusion: Results show thicker wall thickness in pre-CRT scans and differences in wall thickness changes between normal and abnormal esophagus. This demonstrated the potential of esophageal wall thickness as a marker in the tumor CRT response evaluation. This work was supported in part by

  20. RELATIONSHIP BETWEEN ESOPHAGITIS GRADES AND HELICOBACTER PYLORI

    PubMed Central

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

    2016-01-01

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

  1. Do large hiatal hernias affect esophageal peristalsis?

    PubMed Central

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

    2013-01-01

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

  2. Diagnosis and management of esophageal achalasia.

    PubMed

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

    2016-01-01

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

  3. Effect of total laryngectomy on esophageal motility

    SciTech Connect

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

    1981-01-01

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

  4. Misdiagnosis of an α-fetoprotein-producing esophageal carcinoma: A case report and literature review

    PubMed Central

    SUN, NINGBO; YIN, XUNLU; ZHONG, YUREN; ZHANG, XIAOTIAN; XIE, YAN; MENG, XIANGFANG; ZANG, QI

    2016-01-01

    α-fetoprotein (AFP)-producing esophageal carcinoma is a rare type of esophageal cancer, with its characteristics not yet fully clarified. In the present study, a case of esophageal carcinoma was misdiagnosed as an AFP-producing esophageal carcinoma. The patient was a 50-year-old woman who was referred to Qianfoshan Hospital Affiliated to Shandong University in November 2014 with a 3-month history of progressive dysphagia. A chest computed tomography (CT) scan showed thickening of the wall of the esophagus, corresponding regions of luminal stenosis and massive lymph node swelling around the lesser curvature of the esophagus. A laboratory investigation showed that the serum AFP levels of the patient were elevated to 18.97 ng/ml (normal range <12 ng/ml). These laboratory investigation findings combined with the aforementioned pathological diagnosis supported a diagnosis of AFP-producing esophageal carcinoma. An abdominal ultrasound was performed and a cystic low-density measuring 5×4 mm was identified. No metastases were revealed in the liver. The boundary of the focal low density was clear, which indicated a clinical diagnosis of liver cyst. A radical esophagectomy was performed on December 5, 2014. Microscopically, the tumor was a moderately differentiated squamous cell carcinoma invading the serous layer, with no hepatoid features. Immunohistochemistry showed that the cells were diffusely negative for AFP expression. Histopathological examination revealed the absence of hepatoid features. According to these findings, the tumor was diagnosed as a moderately differentiated squamous cell carcinoma. In the present study, the case of a patient with squamous cell carcinoma that was misdiagnosed as an α-fetoprotein-producing esophageal carcinoma was reported, with a review of the literature. PMID:27347186

  5. Three-dimensional imaging of the lower esophageal sphincter in gastroesophageal reflux disease.

    PubMed Central

    Stein, H J; DeMeester, T R; Naspetti, R; Jamieson, J; Perry, R E

    1991-01-01

    The resistance of the lower esophageal sphincter to reflux of gastric juice is determined by the integrated effects of radial pressures exerted over the entire length of the sphincter. This can be quantitated by three-dimensional computerized imaging of sphincter pressures obtained by a pullback of radially oriented pressure transducers and by calculating the volume of this image, in other words, the sphincter pressure vector volume. Validation studies showed that sphincter imaging based on a stepwise pullback of a catheter with four or eight radial side holes is superior to a rapid motorized pullback. Compared with 50 healthy volunteers, the total and abdominal sphincter pressure vector volume was lower in 150 patients with increased esophageal acid exposure (p less than 0.001) and decreased with increasing esophageal mucosal damage (p less than 0.01). Calculation of the sphincter pressure vector volume was superior to standard techniques in identifying a mechanically defective sphincter as the cause of increased esophageal acid exposure, particularly in patients without mucosal damage. The Nissen and Belsey fundoplication increased the total and intra-abdominal sphincter pressure vector volume (p less than 0.001) and normalized the three-dimensional sphincter image. Failure to do so was associated with recurrent or persistent reflux. These data indicate that three-dimensional imaging of the lower esophageal sphincter improves the identification of patients who would benefit from an antireflux procedure. Analysis of the three-dimensional sphincter pressure profile should become the standard for evaluation of the lower esophageal sphincter. PMID:1953093

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

    PubMed

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

    1992-07-01

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

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

    PubMed

    Horodylovska, M I

    2015-01-01

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

  8. Ontogeny of the mouse vocal fold epithelium

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Wu, S X; Wang, L H

    2016-09-23

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

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

    PubMed

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

    2016-01-01

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

  11. Broken Esophageal Stent Successfully Treated by Interventional Radiology Technique

    SciTech Connect

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

    2010-06-15

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

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

    PubMed

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

    2012-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  14. Effect of bisphosphonates on the mandibular bone and gingival epithelium of rats without tooth extraction

    PubMed Central

    DE PONTE, FRANCESCO SAVERIO; CATALFAMO, LUCIANO; MICALI, GREGORIO; RUNCI, MICHELE; CUTRONEO, GIUSEPPINA; VERMIGLIO, GIOVANNA; CENTOFANTI, ANTONIO; RIZZO, GIUSEPPINA

    2016-01-01

    Osteonecrosis of the jaw (ONJ) is an adverse effect of bisphosphonate treatment that has become the subject of increasing investigations, in particular due to its poorly understood pathogenesis. Several experimental studies on animal models have been conducted; however, the majority of these replicate human ONJ following tooth extraction, and describe alterations in the bone and gingival epithelium when necrosis is manifested. The aim of the present study was to analyze the rat mandibular bone and gingival epithelium during 45 days of zoledronate treatment (which is a bisphosphonate agent), without tooth extraction. Intraperitoneal injections of zoledronate acid (0.1 mg/kg) were performed three times a week in normal male Wistar rats (n=20), while a control group of rats (n=20) was treated with saline solution for 45 days. After 7, 15, 30 and 45 days of drug treatment, all rats were sacrificed and hematoxilin and eosin staining, immunofluorescence and scanning electron microscopy analyses were performed. The results of the analyses after 7 and 15 days of treatment were similar in the treatment and control group. After 30 and 45 days of treatment, structural alterations were observed in the bone. No structural alterations to the gingival epithelium were observed. Based on these results, it was hypothesized that low doses of zoledronate act directly on the bone tissues to induce morphological alterations from bone to necrotic tissue following surgical procedures, although no cytotoxic effects were detected in the gingival epithelium. PMID:27168789

  15. In vitro absorption of gamma-globulin by neonatal intestinal epithelium of the pig.

    PubMed

    Lecce, J G

    1966-06-01

    1. An in vitro method, using fluorescent gamma-globulin and everted neonatal pig's intestinal slices, for the study of the active transport of large molecules is described.2. Uptake of gamma-globulin occurred within 15 min and required no exogenous substrates.3. In vitro absorption of gamma-globulin by intestinal epithelium was limited to the neonatal pig and 5-day-old mouse. No uptake was seen in intestines from a mature mouse, a pig with diarrhoea, a normal pig, a mature rabbit, a guinea-pig, a chick, and a chick embryo. Chick embryo yolk sac readily took up gamma-globulin.4. Rings of everted intestinal epithelium remained active (still absorbed gamma-globulin) after incubating for 4-6 hr in balanced salt solution (BSS).5. Uptake of gamma-globulin required oxygen and sodium and was reversibly inhibited by metabolic antagonists such as iodoacetate, arsenate, fluoride, 4,6-dinitro-varphi-cresol, phlorrhizin, anaerobiosis and cold. Under the conditions of the test, large colloidal molecules did not inhibit uptake of gamma-globulin.6. Similar results (although not as clear-cut) with metabolic inhibitors were obtained with preparations of chick embryo yolk sacs.7. Injuring mature pig's intestinal epithelium with surface-active agents did not produce non-specific absorption artifacts that resembled the specific absorption found in immature pig's intestinal epithelium.

  16. Ultrastructural observations on experimentally produced melanin pigmentation of the corneal epithelium.

    PubMed Central

    McCracken, J. S.; Klintworth, G. K.

    1976-01-01

    Melanin pigmentation of the corneal epithelium was induced in pigmented guinea pigs by the topical application of colchicine to their eyes or by corneal cauterization with silver nitrate. With colchicine the pigmentation was preceded by the development of an abnormal corneal epithelium in which numerous cells became arrested in cell division. The corneal melanosis resulted largely from the migration of melanocytes into the corneal epithelium from the normally pigmented contiguous conjunctiva and to a lesser extent from the presence of melanin granules within corneal epithelial cells. In both models a leukocytic and vascular invasion of the cornea proceded and accompanied the migration of melanocytes into the corneal epithelium. Electron microscopy disclosed cells with the same morphology as conjunctival melanocytes between the epithelial cells of the cornea. Mature melanin granules were also present within some squamous epithelial cells as individual granules or as clusters. The ultrastructural findings are viewed in relation to how melanin granules are transferred from melanocytes to epithelial cells. Evidence is presented which suggests that malanin granule transfer may follow the fusion of the membranes of the melanocytes and epithelial cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 PMID:970438

  17. A quantitative electron microscopic analysis of the keratinizing epithelium of noral human hard palate.

    PubMed

    Meyer, M; Schroeder, H E

    1975-01-01

    The epithelium of normal human hard palate was subjected to sterologic analysis. Ten biosies were selected from a total of twenty specimens collected from 9 to 16 year old females, and processed for light- and electron microscopy. At two levels of magnification, electron micrographs were sampled from three strata (basale, spinosum, granulosum) in two locations (epithelial ridges and portions over connective tissue papillae). Stereologic point counting procedures were employed to analyse a total 1560 electron micrographs. In general, the thickness of the palate epithelium was 0.12 mm (over papillae) and 0.31 mm (in ridges), the epithelium is distinctly stratified, and homogeneously ortho-keratinized. From basal to granular layers, the composition of strata revealed decreasing densities of nuclei, mitochondria, membrane-bound organelles and aggregates of free ribosomes. Keratohyalin bodies and membrane coating granules increased, and cytoplasmic filaments with a constant diameter of about 85 A increased from 14 to 30% of cytoplasmic unit volume. The cytoplasmic ground substance occupied a stable 50% of the epithelial cytoplasm in all strata. The composition of basal layers in ridges differed from that over connective tissue papillae. The data are discussed in relation to the observations that (1) an increasing gradient of filament density is not the most characteristic feature of ortho-keratinizing oral epithelium and (2) differences in the degree of differentiation in cells of the stratum basale coincided with the comparable frequency distribution pattern of dividing cells.

  18. A light, transmission and scanning electron microscope study of snuff-treated hamster cheek pouch epithelium.

    PubMed

    Ashrafi, S H; Das, A; Worowongvasu, R; Mehdinejad, B; Waterhouse, J P

    1992-03-01

    The effects of smokeless tobacco (snuff) on hamster cheek mucosa were studied by light microscopy, transmission (TEM) and scanning electron microscopy (SEM). Two grams of commercially available smokeless tobacco were placed into the blind end of the right cheek pouch of each experimental animal, once a day and five days a week for 24 months. The control animals did not receive smokeless tobacco. After 24 months treatment with smokeless tobacco, hamster cheek mucosal epithelium lost its translucency and had become whitish in color. By light microscopy hyperorthokeratosis, prominent granular cell layers with increased keratohyalin granules and hyperplasia were seen. At the ultrastructural level, wider intercellular spaces filled with microvilli, numerous shorter desmosomes, many thin tonofilament bundles, increased number of mitochondria, membrane coating granules and keratohyalin granules were seen in snuff-treated epithelium. The changes in the surface of the epithelium as seen by SEM were the development of an irregular arrangement of the microridges and the disappearance of the normal honeycomb pattern. The microridges were irregular, widened and surrounded the irregular elongated pits. Some smooth areas without microridges and pits were also seen. The long-term histological, TEM and SEM changes induced by smokeless tobacco treatment of the epithelium are well correlated with each other and were similar to those reported in human leukoplakia without dyskeratosis. They imply changes of pathological response resulting from topically applied snuff.

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

    SciTech Connect

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

    1985-10-01

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

  20. Alterations in phenotypic biochemical markers in bladder epithelium during tumorigenesis.

    PubMed

    Rao, J Y; Hemstreet, G P; Hurst, R E; Bonner, R B; Jones, P L; Min, K W; Fradet, Y

    1993-09-01

    Phenotypic biochemical markers of oncogenesis and differentiation were mapped in bladder biopsies to investigate changes that occur in bladder tumorigenesis and to identify markers for increased bladder cancer risk. Touch preparations from biopsy specimens from 30 patients were obtained from tumors, the adjacent bladder epithelium, and random distant bladder epithelium. Markers, including DNA ploidy, epidermal growth factor receptor (EGFR), and oncoproteins, were quantified in individual cells by using quantitative fluorescence image analysis. Cluster analysis revealed the markers fell into three independent groups: (i) G-actin and EGFR; (ii) ploidy, cytology, and p185 (HER-2/neu oncoprotein) (ERBB2); and (iii) p300, a low-grade tumor antigen. Each marker displayed a gradient of abnormality from distant field to adjacent field to tumor. Different patterns for each marker suggested a developmental sequence of bladder cancer oncogenesis; G-actin was altered in 58% of distant biopsies (vs. 0/6 normals, P < 0.001), ploidy and cytology were altered in < 20% of distant fields and approximately 80% of tumors, and the other markers were intermediate. Patterns of EGFR and p185 suggest low-and high-grade tracks diverge early (P < 0.05 by Mann-Whitney U test for EGFR and ANOVA for p185). In conclusion, this study shows that a sequence of phenotypic changes accompanies development and progression of bladder cancers. Biochemical alterations in cells of the bladder field are often detectable before abnormal pathology, and markers previously thought to be limited to tumors were found in the field. The hierarchy of expression may be useful in identifying high-risk patients, assessing completeness of response to therapy, and monitoring and predicting recurrence. PMID:8367495

  1. Evaluation of urgent esophagectomy in esophageal perforation

    PubMed Central

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

    2014-01-01

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

  2. Chemoprevention of esophageal squamous cell carcinoma

    SciTech Connect

    Stoner, Gary D. Wang Lishu; Chen Tong

    2007-11-01

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

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

    SciTech Connect

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

    1993-05-01

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

  4. JAK-STAT6 Pathway Inhibitors Block Eotaxin-3 Secretion by Epithelial Cells and Fibroblasts from Esophageal Eosinophilia Patients: Promising Agents to Improve Inflammation and Prevent Fibrosis in EoE

    PubMed Central

    Cheng, Edaire; Zhang, Xi; Wilson, Kathleen S.; Wang, David H.; Park, Jason Y.; Huo, Xiaofang; Yu, Chunhua; Zhang, Qiuyang; Spechler, Stuart J.; Souza, Rhonda F.

    2016-01-01

    Background Although most studies on treatments for eosinophilic esophagitis (EoE) have focused on effects in the epithelium, EoE is a transmural disease. Eosinophils that infiltrate the subepithelial layers of the esophagus lead to fibrosis and the serious complications of EoE, and current therapies have shown minimal effects on this fibrosis. We aimed to elucidate T helper (Th)2 cytokine effects on esophageal fibroblasts and to explore potential fibroblast-targeted therapies for EoE. Methods We established telomerase-immortalized fibroblasts from human esophageal biopsies. We stimulated these esophageal fibroblasts with Th2 cytokines, and examined effects of omeprazole and inhibitors of the Janus kinase (JAK)—signal transducer and activator of transcription (STAT6) pathway (AS1517499, leflunomide, and ruxolitinib) on STAT6 phosphorylation, STAT6 nuclear translocation, and eotaxin-3 expression. We also measured the effects of these inhibitors in esophageal epithelial cells stimulated with Th2 cytokines. Results As in esophageal epithelial cells, Th2 cytokines increased STAT6 phosphorylation, STAT6 nuclear translocation, eotaxin-3 transcription and protein secretion in esophageal fibroblasts. Unlike in epithelial cells, however, omeprazole did not inhibit cytokine-stimulated eotaxin-3 expression in fibroblasts. In contrast, JAK-STAT6 pathway inhibitors decreased cytokine-stimulated eotaxin-3 expression in both fibroblasts and epithelial cells. Conclusions Omeprazole does not inhibit Th2 cytokine-stimulated eotaxin-3 expression by esophageal fibroblasts, suggesting that PPIs will have limited impact on subepithelial EoE processes such as fibrosis. JAK-STAT6 pathway inhibitors block Th2 cytokine-stimulated eotaxin-3 expression both in fibroblasts and in epithelial cells, suggesting a potential role for JAK-STAT inhibitors in treating both epithelial inflammation and subepithelial fibrosis in EoE. PMID:27310888

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

    PubMed Central

    Michaels, L.; Hyams, V. J.

    1975-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Chen, Keneng

    2014-09-01

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

  9. Activation of the IL-6/JAK/STAT3 signaling pathway in human middle ear cholesteatoma epithelium

    PubMed Central

    Liu, Wei; Xie, Shumin; Chen, Xing; Rao, Xingwang; Ren, Hongmiao; Hu, Bing; Yin, Tuanfang; Xiang, Yuyan; Ren, Jihao

    2014-01-01

    Interleukin-6 (IL-6) is one of the most important cytokines which has been shown to play a critical role in the pathogenesis of cholesteatoma. In this study, we aimed to investigate the expression of interleukin-6 (IL-6) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in middle ear cholesteatoma epithelium in an effort to determine the role of IL-6/JAK/STAT3 signaling pathway in the pathogenesis of cholesteatoma. Immunohistochemistry was used to examine the expression of IL-6 and p-STAT3 in 25 human middle ear cholesteatoma samples and 15 normal external auditory canal (EAC) epithelium specimens. We also analyzed the relation of IL-6 and p-STAT3 expression levels to the degree of bone destruction in cholesteatoma. We found that the expression of IL-6 and p-STAT3 were significantly higher in cholesteatoma epithelium than in normal EAC epithelium (p<0.05). In cholesteatoma epithelium, a significant positive association was observed between IL-6 and p-STAT3 expression (p<0.05). However, no significant relationships were observed between the degree of bone destruction and the levels of IL-6 and p-STAT3 expression (p>0.05). To conclude, our results support the concept that IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma. PMID:24551293

  10. Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

    SciTech Connect

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

    2012-07-01

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

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

    PubMed Central

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

    1975-01-01

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

  12. High resolution microendoscopy for early detection of esophageal cancer in low-resource settings (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Richards-Kortum, Rebecca

    2016-03-01

    Esophageal squamous cell neoplasia (ESCN) is the sixth leading cause of cancer death worldwide. Most deaths due to ESCN occur in developing countries, with highest risk areas in northern China. Lugol's chromoendoscopy (LCE) is the gold-standard for ESCN screening; while the sensitivity of LCE for ESCN is >95%, LCE suffers poor specificity (< 65%) due to false positive findings from inflammatory lesions. High resolution microendoscopy (HRME) uses a low-cost, fiber-optic fluorescence microscope to image morphology of the surface epithelium without need for biopsy. We developed a tablet-interfaced HRME with automated, real-time image analysis. In an in vivo study of 177 patients referred for endoscopy in China, use of the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91% compared to the gold standard of histology.

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

    ClinicalTrials.gov

    2016-09-15

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

  14. Altered Esophageal Mucosal Structure in Patients with Celiac Disease

    PubMed Central

    Pinto-Sánchez, María Inés; Nachman, Fabio D.; Fuxman, Claudia; Iantorno, Guido; Hwang, Hui Jer; Ditaranto, Andrés; Costa, Florencia; Longarini, Gabriela; Wang, Xuan Yu; Huang, Xianxi; Vázquez, Horacio; Moreno, María L.; Niveloni, Sonia; Bercik, Premysl; Smecuol, Edgardo; Mazure, Roberto; Bilder, Claudio; Mauriño, Eduardo C.; Verdu, Elena F.; Bai, Julio C.

    2016-01-01

    Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation. PMID:27446827

  15. Altered Esophageal Mucosal Structure in Patients with Celiac Disease.

    PubMed

    Pinto-Sánchez, María Inés; Nachman, Fabio D; Fuxman, Claudia; Iantorno, Guido; Hwang, Hui Jer; Ditaranto, Andrés; Costa, Florencia; Longarini, Gabriela; Wang, Xuan Yu; Huang, Xianxi; Vázquez, Horacio; Moreno, María L; Niveloni, Sonia; Bercik, Premysl; Smecuol, Edgardo; Mazure, Roberto; Bilder, Claudio; Mauriño, Eduardo C; Verdu, Elena F; Bai, Julio C

    2016-01-01

    Background/Aim. Reflux symptoms (RS) are common in patients with celiac disease (CD), a chronic enteropathy that affects primarily the small intestine. We evaluated mucosal integrity and motility of the lower esophagus as mechanisms contributing to RS generation in patients with CD. Methods. We enrolled newly diagnosed CD patients with and without RS, nonceliac patients with classical reflux disease (GERD), and controls (without RS). Endoscopic biopsies from the distal esophagus were assessed for dilated intercellular space (DIS) by light microscopy and electron microscopy. Tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3) was determined using qRT-PCR. Results. DIS scores were higher in patients with active CD than in controls, but similar to GERD patients. The altered DIS was found even in CD patients without RS and normalized after one year of a gluten-free diet. CD patients with and without RS had lower expression of ZO-1 than controls. The expression of CLDN-2 and CLDN-3 was similar in CD and GERD patients. Conclusions. Our study shows that patients with active CD have altered esophageal mucosal integrity, independently of the presence of RS. The altered expression of ZO-1 may underlie loss of TJ integrity in the esophageal mucosa and may contribute to RS generation. PMID:27446827

  16. Esophageal surgery in minimally invasive era

    PubMed Central

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

    2016-01-01

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

  17. The Tumor Microenvironment in Esophageal Cancer

    PubMed Central

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

    2016-01-01

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

  18. Chronic Recurrent Esophageal Diverticulitis - A Rare Entity

    PubMed Central

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

    2013-01-01

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

  19. Pharmacological Management of Esophageal Food Bolus Impaction

    PubMed Central

    Khayyat, Yasir Mohammed

    2013-01-01

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

  20. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia

    PubMed Central

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E.; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  1. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    PubMed

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  2. Zidovudine, abacavir and lamivudine increase the radiosensitivity of human esophageal squamous cancer cell lines.

    PubMed

    Chen, Xuan; Wang, Cong; Guan, Shanghui; Liu, Yuan; Han, Lihui; Cheng, Yufeng

    2016-07-01

    Telomerase is a type of reverse transcriptase that is overexpressed in almost all human tumor cells, but not in normal tissues, which provides an opportunity for radiosensitization targeting telomerase. Zidovudine, abacavir and lamivudine are reverse transcriptase inhibitors that have been applied in clinical practice for several years. We sought to explore the radiosensitization effect of these three drugs on human esophageal cancer cell lines. Eca109 and Eca9706 cells were treated with zidovudine, abacavir and lamivudine for 48 h before irradiation was administered. Samples were collected 1 h after irradiation. Clonal efficiency assay was used to evaluate the effect of the combination of these drugs with radiation doses of 2, 4, 6 and 8 Gy. DNA damage was measured by comet assay. Telomerase activity (TA) and relative telomere length (TL) were detected and evaluated by real-time PCR. Apoptosis rates were assessed by flow cytometric analysis. The results showed that all the drugs tested sensitized the esophageal squamous cell carcinoma (ESCC) cell lines to radiation through an increase in radiation-induced DNA damage and cell apoptosis, deregulation of TA and decreasing the shortened TL caused by radiation. Each of the drugs investigated (zidovudine, abacavir and lamivudine) could be used for sensitizing human esophageal cancer cell lines to radiation. Consequently, the present study supports the potential of these three drugs as therapeutic agents for the radiosensitization of esophageal squamous cell cancer. PMID:27220342

  3. Protective effects of melatonin against caustic esophageal burn injury in rats.

    PubMed

    Larios-Arceo, F; Ortiz, G G; Huerta, M; Leal-Cortés, C; Saldaña, J A; Bitzer-Quintero, O K; Rodríguez-Reynoso, S

    2008-09-01

    Caustic ingestion is one of the most life-threatening events in the pediatric age group, which requires the immediate management and subsequent treatment of its most significant complication, i.e. alterations in esophageal structure. We investigated whether melatonin could reduce the esophageal burn damage induced by sodium hydroxide. It was assumed that melatonin could be effective because of its function as a direct free radical scavenger, its antioxidative actions and its ability to diminish tissue hydroxyproline (HP) levels. Esophageal burns were induced in male rats by the administration of 10% sodium hydroxide. Lipid peroxidation (LPO) products were then measured at the following times: 0, 1, 6, 24, 48 and 72 hr after treatment. Tissue HP concentrations in the injured area were assessed at 14 days after the administration of sodium hydroxide. The groups received either systemic melatonin or normal saline. There were two, non-ischemic, sham control groups treated with or without melatonin. LPO products, malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA), increased immediately after the administration of sodium hydroxide; this indicates the participation of free radicals in the development of damage. Melatonin diminished the oxidative response and the amount of HP in the late phase of the lesion. Melatonin reduced oxidative damage in the early phase of the esophageal burns induced by sodium hydroxide.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  7. Endoscopic treatment of esophageal achalasia

    PubMed Central

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

    2016-01-01

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

  8. Detection of serum p53 antibodies in patients with esophageal squamous cell carcinoma: correlation with clinicopathologic features and tumor markers.

    PubMed

    Shimada, H; Nakajima, K; Ochiai, T; Koide, Y; Okazumi, S I; Matsubara, H; Takeda, A; Miyazawa, Y; Arima, M; Isono, K

    1998-01-01

    The significance of serum p53-Abs in patients with esophageal squamous cell carcinoma was determined. Examination of clinicopathological features and assessment of tumor marker sensitivities of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag) and CYFRA21-1 were performed. Thirty-three (58%) of 57 patients were positive for serum p53-Abs, however, no relation with cancer progression existed. Fourteen of the 33 sero-positive patients revealed normal levels of all tumor markers tested. Thus, serum p53-Abs appears to be a useful marker for the detection of esophageal squamous cell carcinoma.

  9. An Overview of the Diagnosis and Management of Eosinophilic Esophagitis

    PubMed Central

    Singla, Manish B; Moawad, Fouad J

    2016-01-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by symptoms of esophageal dysfunction and eosinophilic infiltration of the esophageal mucosa. The diagnosis requires esophageal biopsies demonstrating at least 15 eosinophils per high-powered field following a course of high-dose proton pump inhibitors. Management of EoE consists of the three Ds: drugs, dietary therapy, and esophageal dilation. In this review, we discuss the epidemiology, pathogenesis, diagnosis, and treatment of EoE to include the role of emerging therapies. PMID:26986655

  10. Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma

    PubMed Central

    Gannot, G; Gannot, I; Vered, H; Buchner, A; Keisari, Y

    2002-01-01

    In the present study, epithelium derived lesions of various pathological manifestations were examined histologically and immunohistochemically for mononuclear cell infiltration. The infiltrate under the transformed epithelium of oral lesions, was examined for differences in the composition of immune mononuclear cells as the epithelium moves from hyperkeratosis through various degrees of dysplasia to squamous cell carcinoma. The study was performed on 53 human tongue tissues diagnosed as hyperkeratosis (11 cases), mild dysplasia (nine cases), moderate and severe dysplasia (14 cases) and squamous cell carcinoma (19 cases). A similar analysis was performed on 30 parotid gland tissues diagnosed as pleomorphic adenoma (14 cases) and carcinoma ex-pleomorphic adenoma (16 cases). Immunohistochemical analysis of various surface markers of the tumour infiltrating immune cells was performed and correlated with the transformation level as defined by morphology and the expression of p53 in the epithelium. The results revealed that, in the tongue lesions, the changes in the epithelium from normal appearance to transformed were accompanied by a corresponding increase in the infiltration of CD4, CD8, CD14, CD19+20, and HLA/DR positive cells. The most significant change was an increase in B lymphocytes in tongue lesions, that was in accordance with the transformation level (P<0.001). In the salivary gland, a significant number of cases did not show an infiltrate. In cases where an infiltrate was present, a similar pattern was observed and the more malignant tissues exhibited a higher degree of immune cell infiltration. British Journal of Cancer (2002) 86, 1444–1448. DOI: 10.1038/sj/bjc/6600282 www.bjcancer.com © 2002 Cancer Research UK PMID:11986779

  11. Congenital esophageal stenosis owing to tracheobronchial remnants

    PubMed Central

    Rebelo, Priscila Guyt; Ormonde, João Victor C.; Ormonde, João Baptista C.

    2013-01-01

    OBJECTIVE To emphasize the need of an accurate diagnosis of congenital esophageal stenosis due to tracheobronchial remnants, since its treatment differs from other types of congenital narrowing. CASE DESCRIPTION Four cases of lower congenital esophageal stenosis due to tracheobronchial remnants, whose definitive diagnosis was made by histopathology. Except for the last case, in which a concomitant anti-reflux surgery was not performed, all had a favorable outcome after resection and anastomosis of the esophagus. COMMENTS The congenital esophageal stenosis is an intrinsic narrowing of the organâ€(tm)s wall associated with its structural malformation. The condition can be caused by tracheobronchial remnants, fibromuscular stenosis or membranous diaphragm and the first symptom is dysphagia after the introduction of solid food in the diet. The first-choice treatment to tracheobronchial remnants cases is the surgical resection and end-to-end anastomosis of the esophagus. PMID:24142326

  12. Minimally invasive surgery for esophageal cancer.

    PubMed

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

    2008-10-01

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

  13. Endoscopic options for early stage esophageal cancer

    PubMed Central

    Shah, Pari M.

    2015-01-01

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

  14. MicroRNA-20b (miR-20b) Promotes the Proliferation, Migration, Invasion, and Tumorigenicity in Esophageal Cancer Cells via the Regulation of Phosphatase and Tensin Homologue Expression

    PubMed Central

    Xiao, Bin

    2016-01-01

    Increasing evidence has indicated that many microRNAs participate in the development and progression of esophageal cancer and gene expression regulation. MicroRNA-20b (miR-20b) has been reported to be aberrantly expressed in various cancers, but its exact role in esophageal cancer cells remains unclear so far. Therefore, we detected the levels of miR-20b in esophageal tumor tissues and their adjacent normal tissues, and various esophageal cancer cell lines by qRT-PCR. We also explored the effects of miR-20b on cell proliferation, migration, invasion and tumorigenicity of esophageal carcinoma cells through transfection with miR-20b mimics or inhibitor to upregulate or downregulate miR-20b expression in the esophageal cancer cells Eca-109 and KYSE-150, respectively. Additionally, the 3'-untranslated region (3'-UTR) of phosphatase and tensin homologue (PTEN) binding with miR-20b was analyzed by dual-luciferase reporter assays. The results indicated that miR-20b expression level in esophageal tumor tissues was significantly increased compared with their neighboring normal tissues, but its expression was inverse with PTEN protein expression. Luciferase assays confirmed that the 3'-UTR of PTEN was a target of miR-20b in esophageal cancer cells. MiR-20b upregulation promoted cell proliferation, migration, invasiveness, and tumor growth, and decreased apoptosis, and reduced PTEN protein level but not mRNA expression in Eca-109 cells. Conversely, downregulation of miR-20b suppressed these processes in KYSE-150 cells, and enhanced PTEN protein expression. These data indicate that miR-20b plays important roles in tumorigenesis of esophageal cancer possibly via regulation of PTEN expression, and it may be a potential therapeutic target for esophageal cancer treatment. PMID:27701465

  15. Spatially limited growth of an epithelium

    NASA Astrophysics Data System (ADS)

    Deforet, Maxime; Cochet, Olivier; Buguin, Axel; Silberzan, Pascal

    2012-02-01

    We present a study dealing with the growth of an epithelium on a spatially limited adhesive substrate. Adhesive patterns (typical size: 50μm to 500μm) are created by micro-fabrication techniques: A protein repellent polymeric gel homogeneously grafted on a coverslip is selectively ablated by plasma treatment through a thin layer of photoresist. The technique achieves a high resolution of patterning (around 2μm). After seeding cells (MDCK) on circular adhesive patterns, we let the monolayer grow for 30 hours after reaching the confluence. We use physical descriptors to describe migration and compaction. Two days after the confluence, we observe and characterize by confocal microscopy, the appearance of a tridimensionnal assembly of cells in the peripherical zone of the adhesive pattern (a ``rim''). Moreover using other patterns, the existence of a tissue line tension and internal pressure is investigated.

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

    SciTech Connect

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

    1985-05-01

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

  17. [Endoscopic ultrasonic diagnosis of esophageal cancer].

    PubMed

    Kouzu, T; Ogino, Y; Isono, K

    1986-08-01

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

  18. Eosinophilic esophagitis in adults: An update

    PubMed Central

    Ahmed, Monjur

    2016-01-01

    Eosinophilic esophagitis is a worldwide chronic allergic disease of the esophagus. In the last decade, there is an epidemic of this entity in the western world. Mostly seen in children and young adults, patients present with dysphagia or food impaction in the emergency room. Characteristic endoscopic findings, esophageal eosinophilia and non-responsiveness to proton pump inhibitors help make the diagnosis. Avoidance of food allergens, administration of steroidal anti-inflammatory medications and dilation of the esophagus are the mainstays of treatment. Investigations are ongoing for mucosal healing and optimum maintenance treatment. PMID:27158535

  19. Esophageal web in Plummer-Vinson syndrome.

    PubMed

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

    1988-09-01

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

  20. High-Resolution Manometry Evaluation of the Pharynx and Upper Esophageal Sphincter Motility in Patients with Achalasia.

    PubMed

    Menezes, Mariano A; Herbella, Fernando A M; Patti, Marco G

    2015-10-01

    The motility of the pharynx and upper esophageal sphincter (UES) is still poorly understood. It is also unclear if the motility of this area may be compromised in patients with achalasia. This study aims to evaluate the motility of the pharynx, UES, and proximal esophagus in patients with esophageal achalasia. Sixty patients with achalasia underwent high-resolution manometry (HRM) (52 % females, mean age 54 years). Esophageal dilatation was classified according to the radiologic diameter in Type I (<4 cm): 6 %; Type II (4-7 cm): 36 %; Type III (7-10 cm): 34 %; and Type IV (>10 cm): 24 %. HRM classified 43 % of the patients as Chicago Type I and 57 % as Type II. Manometric parameters were compared to normal values obtained from a previous study in volunteers. The motility of the velopharynx showed short, premature, and hypertonic contraction. The epiglottis also showed hypertonic contraction. The UES had increased residual pressure. Chicago classification Type II patients had higher UES residual pressure (p = 0.03). The degree of esophageal dilatation did not correlate with manometric parameters. Achalasia may affect the motility of the pharyngo-upper esophageal area. The changes observed may represent functional alterations to prevent aspiration, especially in patients with Chicago classification Type II achalasia.

  1. Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

    PubMed

    Shahrabi-Farahani, Shokoufeh; Gallottini, Marina; Martins, Fabiana; Li, Erik; Mudge, Dayna R; Nakayama, Hironao; Hida, Kyoko; Panigrahy, Dipak; D'Amore, Patricia A; Bielenberg, Diane R

    2016-04-01

    Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells. PMID:26877262

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

    PubMed Central

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

    2016-01-01

    Epithelial morphogenesis and stability are essential for normal development and organ homeostasis. The mouse neural plate is a cuboidal epithelium that remodels into a columnar pseudostratified epithelium over the course of 24 hr. Here we show that the transition to a columnar epithelium fails in mutant embryos that lack the tumor suppressor PTEN, although proliferation, patterning and apical-basal polarity markers are normal in the mutants. The Pten phenotype is mimicked by constitutive activation of PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kinases AKT and mTORC1. High resolution imaging shows that PTEN is required for stabilization of planar cell packing in the neural plate and for the formation of stable apical-basal microtubule arrays. The data suggest that appropriate levels of membrane-associated PDPK1 are required for stabilization of apical junctions, which promotes cell elongation, during epithelial morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.12034.001 PMID:26809587

  3. Challenges and opportunities for tissue-engineering polarized epithelium.

    PubMed

    Paz, Ana C; Soleas, John; Poon, James C H; Trieu, Dennis; Waddell, Thomas K; McGuigan, Alison P

    2014-02-01

    The epithelium is one of the most important tissue types in the body and the specific organization of the epithelial cells in these tissues is important for achieving appropriate function. Since many tissues contain an epithelial component, engineering functional epithelium and understanding the factors that control epithelial maturation and organization are important for generating whole artificial organ replacements. Furthermore, disruption of the cellular organization leads to tissue malfunction and disease; therefore, engineered epithelium could provide a valuable in vitro model to study disease phenotypes. Despite the importance of epithelial tissues, a surprisingly limited amount of effort has been focused on organizing epithelial cells into artificial polarized epithelium with an appropriate structure that resembles that seen in vivo. In this review, we provide an overview of epithelial tissue organization and highlight the importance of cell polarization to achieve appropriate epithelium function. We next describe the in vitro models that exist to create polarized epithelium and summarize attempts to engineer artificial epithelium for clinical use. Finally, we highlight the opportunities that exist to translate strategies from tissue engineering other tissues to generate polarized epithelium with a functional structure.

  4. Localization and Expression of Zonula Occludins-1 in the Rabbit Corneal Epithelium following Exposure to Benzalkonium Chloride

    PubMed Central

    Zhang, Zhenhao; Chen, Lelei; Xie, Hui; Dong, Nuo; Chen, Yongxiong; Liu, Zuguo

    2012-01-01

    Preservatives are a major component of the ophthalmic preparations in multi-dose bottles. The purpose of this study was to investigate the acute effect of benzalkonium chloride (BAC), a common preservative used in ophthalmic preparations, on the localization and expression of zonula occludens (ZO)-1 in the rabbit corneal epithelium in vivo. BAC at 0.005%, 0.01%, or 0.02% was topically applied to one eye each of albino rabbits at 5 min intervals for a total of 3 times. The contralateral untreated eyes served as controls. The following clinical indications were evaluated: Schirmer test, tear break-up time (BUT), fluorescein and rose Bengal staining. The structure of central cornea was examined by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance and permeability to carboxy fluorescein. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of ZO-1, 2, occludin, claudin-1, Ki67 and cell apoptosis in the epithelium. The expression of ZO-1 in the corneal epithelium was also examined by western blot and reverse transcription-polymerase chain reaction analyses. Exposure to BAC resulted in higher rose Bengal staining scores while no significant changes in BUT, Schirmer and corneal florescein scores. It also induced corneal epithelial cell damage, dispersion of ZO-1 and ZO-2 from their normal locus at the superficial layer and disruption of epithelial barrier function. However, the amounts of ZO-1 mRNA and protein in the corneal epithelium were not affected by BAC treatment. Exposure to BAC can quickly impair the corneal epithelium without tear deficiency. BAC disrupts the tight junctions of corneal epithelium between superficial cells in the rabbit corneal epithelium in vivo. PMID:22815857

  5. Bronchial epithelium in children: a key player in asthma.

    PubMed

    Carsin, Ania; Mazenq, Julie; Ilstad, Alexandra; Dubus, Jean-Christophe; Chanez, Pascal; Gras, Delphine

    2016-06-01

    Bronchial epithelium is a key element of the respiratory airways. It constitutes the interface between the environment and the host. It is a physical barrier with many chemical and immunological properties. The bronchial epithelium is abnormal in asthma, even in children. It represents a key component promoting airway inflammation and remodelling that can lead to chronic symptoms. In this review, we present an overview of bronchial epithelium and how to study it, with a specific focus on children. We report physical, chemical and immunological properties from ex vivo and in vitro studies. The responses to various deleterious agents, such as viruses or allergens, may lead to persistent abnormalities orchestrated by bronchial epithelial cells. As epithelium dysfunctions occur early in asthma, reprogramming the epithelium may represent an ambitious goal to induce asthma remission in children.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-02-01

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

  8. Do Airway Epithelium Air–Liquid Cultures Represent the In Vivo Airway Epithelium Transcriptome?

    PubMed Central

    Dvorak, Anna; Tilley, Ann E.; Shaykhiev, Renat; Wang, Rui; Crystal, Ronald G.

    2011-01-01

    Human airway epithelial cells cultured in vitro at the air–liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, and produces mucin. These cells are widely used in models of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at the ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed that global gene expression correlated well between ALI cells and brushed cells, but with some differences. Gene expression patterns mirrored differences in proportions of cell types (ALIs have higher percentages of basal cells, whereas brushed cells have higher percentages of ciliated cells), that is, ALI cells expressed higher levels of basal cell–related genes, and brushed cells expressed higher levels of cilia-related genes. Pathway analysis showed that ALI cells had increased expression of cell cycle and proliferation genes, whereas brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells provide a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences between in vitro and in vivo environments need to be considered. PMID:20525805

  9. Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma.

    PubMed

    Chen, Tiantian; Cheng, Hongwei; Chen, Xingdong; Yuan, Ziyu; Yang, Xiaorong; Zhuang, Maoqiang; Lu, Ming; Jin, Li; Ye, Weimin

    2015-01-01

    A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire, and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42-2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74-36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54-2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk.

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

    PubMed Central

    Eluri, Swathi; Dellon, Evan S.

    2015-01-01

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

  11. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    PubMed Central

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the

  12. An immunohistological study of cytokeratin 20 in human and mammalian oral epithelium.

    PubMed

    Barrett, A W; Cort, E M; Patel, P; Berkovitz, B K

    2000-10-01

    Cytokeratin (CK) 20 is a low molecular-weight intermediate filament reportedly expressed only by benign and malignant gastrointestinal epithelium, urothelium and Merkel cells. The main aims here were to map its expression in normal oral mucosa of humans and other mammals, and to determine whether it was expressed by abnormal human oral epithelium. Salivary and odontogenic epithelium were also analysed. An immunoperoxidase method was used on wax-embedded and cryostat sections. In addition, double-labelling experiments were undertaken to determine the association between CK 20 expression and that of CK 8/18 or S100 protein. Normal human oral mucosa from four sites, together with abdominal skin, was studied in autopsy samples from 32 individuals. CK 20-positive, basally situated, round or angular cells, consistent with Merkel cells, were recorded in 24/32 (75.0%) samples of mandibular gingiva, 25/32 (78.1%) samples of hard palate, 7/32 (21.9%) samples of buccal mucosa, 0/32 samples of lateral border of tongue, and 2/32 (6.3%) samples of abdominal skin. Double-labelling showed that all CK 20-positive Merkel cells also expressed CK 8/18 and S100. The only other cells to express CK 20 were human taste buds. There was no expression by dysplastic or invasive oral epithelium from biopsy samples. Colonic mucosa showed luminal-cell positivity in man, marmoset, ferret, rabbit and guinea-pig, but oral mucosa was universally negative in non-human species. It is concluded that in oral mucosa CK 20 is a specific marker of Merkel cells and taste buds, that Merkel cells are more frequently present in keratinized than non-keratinized oral mucosa, that CK 20-positive Merkel cells are also S100-positive, that there may be interspecies variations in CK 20 polypeptide composition and that, by contrast to urothelium, CK 20 has no value in the diagnosis of oral epithelial dysplasia.

  13. Trachea Epithelium as a “Canary” for Cigarette Smoking-induced Biologic Phenotype of the Small Airway Epithelium*

    PubMed Central

    Turetz, Meredith L.; O’Connor, Timothy P.; Tilley, Ann E.; Strulovici-Barel, Yael; Salit, Jacqueline; Dang, David; Teater, Matthew; Mezey, Jason; Clark, Andrew G.; Crystal, Ronald G.

    2013-01-01

    The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n=26) and healthy smokers (n=19, 27 ± 15 pack-yr). Gene expression differences (fold-change >1.5, p<0.01, Benjamini-Hochberg correction) were assessed with Affymetrix microarrays. 1,057 probe sets were differentially expressed in healthy smokers vs nonsmokers, representing >500 genes. Trachea gene expression was compared to an independent group of small airway epithelial samples (n=23 healthy nonsmokers, n=19 healthy smokers, 25 ± 12 pack-yr). The trachea epithelium is more sensitive to smoking, responding with 3-fold more differentially-expressed genes than small airway epithelium. The trachea transcriptome paralleled the small airway epithelium, with 156 of 167 (93%) genes that are significantly upand down-regulated by smoking in the small airway epithelium showing similar direction and magnitude of response to smoking in the trachea. Trachea epithelium can be obtained without conscious sedation, representing a less invasive surrogate “canary” for smoking-induced changes in the small airway epithelium. This should prove useful in epidemiologic studies correlating gene expression with clinical outcome in assessing smoking-induced lung disease. PMID:20443905

  14. Predicting malignant transformation of esophageal squamous cell lesions by combined biomarkers in an endoscopic screening program

    PubMed Central

    Zhang, Hao; Li, Hao; Ma, Qing; Yang, Fang-Yan; Diao, Tao-Yu

    2016-01-01

    AIM To determine the association of p53, carcinoembryonic antigen (CEA) and CA19-9 protein expression with esophageal carcinogenesis. METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia (BCH), 247 with low-grade dysplasia (LGD), 51 with high-grade dysplasia (HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROC curve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions. RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH. CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions.

  15. Histomorphological and Immunophenotypic Features of Pill-Induced Esophagitis

    PubMed Central

    Kim, Su Hwan; Kim, Won; Lee, Kook Lae; Byeon, Sun-ju; Choi, Euno; Chang, Mee Soo

    2015-01-01

    The aim of this study was to investigate histomorphological and immunophenotypic features in pill-induced esophagitis. We comparatively evaluated the histomorphological, immunophenotypic features of pill-induced esophagitis vs. reflux esophagitis, as well as clinical information and endoscopic findings. Fifty-two tissue pieces from 22 cases of pill-induced esophagitis, 46 pieces from 20 reflux esophagitis, and 16 pieces from 14 control samples were subjected to immunohistochemistry for inflammatory infiltrates (CD3 for T lymphocyte, CD20 for B lymphocyte, CD56 for NK cell, CD68 for macrophage, CD117 for mast cell) and eosinophil chemotaxis-associated proteins (Erk, leptin, leptin receptor, pSTAT3, phospho-mTOR). As a result, Histomorphology showed that a diffuse pattern of dilated intercellular spaces was more frequently observed in pill-induced esophagitis, while reactive atypia and subepithelial papillary elongation were more often found in reflux esophagitis (P < 0.05, respectively). Interestingly, intraepithelial eosinophilic microabscess, intraepithelial pustule and diffuse pattern of dilated intercellular spaces were observed in 14% (3 cases), 9% (2 cases) and 32% (7 cases) of pill-induced esophagitis, respectively, but in no cases of reflux esophagitis. Regarding intraepithelial inflammatory infiltrates in pill-induced esophagitis, T lymphocytes were the most common cells, followed by eosinophil; 11 and 7 in one x400 power field, respectively. Intraepithelial pSTAT3-positive pattern was more frequently observed in pill-induced esophagitis than in reflux esophagitis, at 45% (10 cases) versus 10% (2 cases), respectively (P < 0.05). Considering the distal esophageal lesion only, intraepithelial pustule, diffuse dilated intercellular spaces and stromal macrophages were more frequently found in distal pill-induced esophagitis, whereas reactive atypia and intraepithelial mast cells in reflux esophagitis (P < 0.05, respectively). In conclusion, diffuse dilated

  16. Preoperative therapy in locally advanced esophageal cancer

    PubMed Central

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

    2016-01-01

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

  17. Esophageal testing: What we have so far

    PubMed Central

    de Bortoli, Nicola; Martinucci, Irene; Bertani, Lorenzo; Russo, Salvatore; Franchi, Riccardo; Furnari, Manuele; Tolone, Salvatore; Bodini, Giorgia; Bolognesi, Valeria; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino; Savarino, Edoardo Vincenzo

    2016-01-01

    Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising. PMID:26909230

  18. 21 CFR 868.5650 - Esophageal obturator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  19. 21 CFR 868.5650 - Esophageal obturator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  20. Does surgery correct esophageal motor dysfunction in gastroesophageal reflux

    SciTech Connect

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

    1981-09-01

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

  1. Effect of palonosetron (5HT-3 antagonist) and pantoprazole (proton pump inhibitor) against surgical esophagitis induced by forestomach and pylorus ligation in albino rats.

    PubMed

    Kumar, A; Gautam, S; Rawat, J K; Singh, M; Saraf, S A; Kaithwas, G

    2016-01-01

    This study was embarked upon to evaluate the effects of pantoprazole and palonosetron on experimental esophagitis in albino wistar rats. Groups of rats, fasted for 36 h, were subjected to pylorus and forestomach ligation, supervened by treatment with normal saline (3 ml/kg, po, sham control), esophagitis control (3 ml/kg, po), pantoprazole (30 mg/kg, po), palonosetron (0.5 mg/kg, po), and their combination. Animals were sacrificed after 12 h and appraised for the volume of gastric juices, total acidity, free acidity, and esophagitis index. Esophageal tissues were further figured out biochemically for markers of oxidative stress and inflammatory mediators. The combination therapy comparably inhibited the esophagitis index (52.86%), gastric volume (66.04%), free acidity (43.76%), and total acidity (42.60%) in comparison with toxic control. The combination therapy also subsidized the biochemical and inflammatory markers to the purview less than toxic control. The morphological changes were scrutinized by scanning electron microscopy and were observed to demonstrate momentous protection by the amalgamation therapy. Combination therapy with pantoprazole and palonosetron flaunted sententious protection against experimental esophagitis.

  2. Simple epithelium keratins are required for maintenance of hepatocyte integrity.

    PubMed Central

    Loranger, A.; Duclos, S.; Grenier, A.; Price, J.; Wilson-Heiner, M.; Baribault, H.; Marceau, N.

    1997-01-01

    Keratin 8 (K8)-deficient adult mice develop a severe disease of the gastrointestinal tract characterized mainly by colorectal hyperplasia and inflammation. Given that hepatocytes contain K8/K18 heteropolymers only, this animal model was used to assess the contribution of these simple epithelium keratins to hepatocyte structural and functional integrity. Homozygous mutant (HMZ), heterozygous, and wild-type (WT) mice were examined for hepatocyte structural and metabolic features and their survival to partial hepatectomy. Except for the presence of few necrotic foci, no other tissular or cellular alterations were observed in nonhepatectomized HMZ mouse livers; glycogen and lipid peroxidation levels were essentially normal, but a small reduction in bile flow was observed. In response to a single pentobarbital injection, HMZ mice had longer sleeping times than heterozygous and WT mice. After a two-thirds partial hepatectomy under pentobarbital anesthesia, all HMZ mice died within a few hours, whereas those anesthetized with ether survived for 1 to 2 days. One hour after hepatectomy after pentobarbital anesthesia, many hepatocytes contained erythrocytes and large vacuoles in the cytoplasm, which suggests damage at the plasma membrane level in response to a sudden increase in portal blood flow. In line with these findings, an uptake of trypan blue by HMZ but not WT mouse hepatocytes was observed during a 10 ml/minute perfusion via the portal vein with a dye-supplemented buffer. Subsequent cellular dispersion led to viable WT mouse hepatocytes but largely nonviable HMZ mouse hepatocytes. Better viability was obtained at lower perfusion rates. Partially hepatectomized heterozygous mice developed liver steatosis, a condition that was not associated with a change in K8 content but perhaps linked to the presence of the neo gene. Transgenic HMZ mouse rescue experiments with a full-length K8 gene confirmed that the phenotypic alterations observed in partially hepatectomized HMZ

  3. Biochemical indicators of caustic ingestion and/or accompanying esophageal injury in children.

    PubMed

    Otçu, Selçuk; Karnak, Ibrahim; Tanyel, Feridun Cahit; Senocak, Mehmet Emin; Büyükpamukçu, Nebil

    2003-01-01

    A prospective clinical study was conducted to evaluate whether or not any biochemical predictor of caustic ingestion and complicating esophageal injury exists. Children who were admitted to the hospital within 24 hours following caustic substance ingestion between 1994 and 2000 inclusive were evaluated. The ingested substance and complaints upon admission were noted. Groups were constructed according to the ingested substances such as household bleach (HB) (Group 1), acid (Group 2) or alkali ingestion (Group 3). Full biochemical analyses, chest X-ray and blood gas estimations were obtained and children were evaluated endoscopically. Seventy-eight children were studied. There were 19, 20 and 39 children in Groups 1, 2, and 3, respectively. There were no sex or age differences among groups (p>0.05). Esophagogastric injury was not encountered in Group 1. Second degree injury was present in 12 and 11 children in Group 2 and Group 3, respectively. Blood pH level was decreased in Group 1 (p=0.013), but not different in Groups 2 and 3 (p>0.05). pH did not differ in patients with or without esophageal injury (p>0.05). While serum uric acid values were significantly increased in children with esophageal burn (p=0.001), serum phosphorus and alkaline phosphatase levels were significantly decreased in children with esophageal injury (p=0.01 and p=0.019, respectively). Blood bicarbonate and serum potassium, chloride, urea nitrogen, creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, lactic dehydrogenase, calcium, glucose, protein, albumin and bilirubin levels did not differ between group (p>0.05), nor between patients with or without complicating esophageal injury (p>0.05). Low serum pH level is an indicator of HB ingestion. Routine endoscopy may not be necessary in children with normal blood pH values after ingestion. Although normal values of pH, uric acid, phosphorus and alkaline phosphatase levels do not rule out ingestion of an acid-or alkali

  4. Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

    2014-02-01

    The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

  5. Reversal of negative pressure ventilation-induced lower esophageal sphincter dysfunction with metoclopramide.

    PubMed

    Marino, W D; Pitchumoni, C S

    1992-02-01

    We have previously demonstrated that lower esophageal sphincter (LES) dysfunction is induced in healthy volunteers placed in negative pressure body ventilators. This is important, because regurgitation of gastric contents and peptic esophagitis are frequent complications of the use of such ventilators. The present study was conducted to determine whether LES dysfunction during the use of these ventilators also occurs in patients with chronic respiratory failure, and whether this dysfunction can be pharmacologically reversed. Seven patients with documented chronic respiratory failure due to COPD were studied. After an overnight fast, esophageal, LES, and gastric pressures were simultaneously recorded in the unassisted state and during mechanically assisted ventilation, after which 10 mg iv metoclopramide were administered to each patient, and pressure recordings were continued for 1 h more. In all seven patients, baseline LES pressures were in the normal range. During the inspiratory cycle of mechanical ventilation, five of the seven patients demonstrated a significant reduction in LES pressure, whereas it was unchanged in the other two. Within 15 min of metoclopramide administration, there was an increase in LES pressure to baseline levels in the five patients in which a significant decrease in LES pressure had occurred. Metoclopramide did not have any effect on the LES pressure of the other two patients. Thus, we conclude that in patients with chronic respiratory failure, as in normals, there is a subset of individuals in whom negative pressure mechanical ventilatory assistance induces dysfunction of the LES, and that this dysfunction is reversible with metoclopramide.

  6. Stem cells of the skin epithelium

    PubMed Central

    Alonso, Laura; Fuchs, Elaine

    2003-01-01

    Tissue stem cells form the cellular base for organ homeostasis and repair. Stem cells have the unusual ability to renew themselves over the lifetime of the organ while producing daughter cells that differentiate into one or multiple lineages. Difficult to identify and characterize in any tissue, these cells are nonetheless hotly pursued because they hold the potential promise of therapeutic reprogramming to grow human tissue in vitro, for the treatment of human disease. The mammalian skin epithelium exhibits remarkable turnover, punctuated by periods of even more rapid production after injury due to burn or wounding. The stem cells responsible for supplying this tissue with cellular substrate are not yet easily distinguishable from neighboring cells. However, in recent years a significant body of work has begun to characterize the skin epithelial stem cells, both in tissue culture and in mouse and human skin. Some epithelial cells cultured from skin exhibit prodigious proliferative potential; in fact, for >20 years now, cultured human skin has been used as a source of new skin to engraft onto damaged areas of burn patients, representing one of the first therapeutic uses of stem cells. Cell fate choices, including both self-renewal and differentiation, are crucial biological features of stem cells that are still poorly understood. Skin epithelial stem cells represent a ripe target for research into the fundamental mechanisms underlying these important processes. PMID:12913119

  7. Human vomeronasal epithelium development: An immunohistochemical overview.

    PubMed

    Dénes, Lóránd; Pap, Zsuzsanna; Szántó, Annamária; Gergely, István; Pop, Tudor Sorin

    2015-06-01

    The vomeronasal organ (VNO) is the receptor structure of the vomeronasal system (VNS) in vertebrates. It is found bilaterally in the submucosa of the inferior part of the nasal septum. There are ongoing controversies regarding the functionality of this organ in humans. In this study we propose the immunohistochemical evaluation of changes in components of the human vomeronasal epithelium during foetal development. We used 45 foetuses of different age, which were included in three age groups. After VNO identification immunohistochemical reactions were performed using primary antibodies against the following: neuron specific enolase, calretinin, neurofilament, chromogranin, synaptophysin, cytokeratin 7, pan-cytokeratin and S100 protein. Digital slides were obtained and following colorimetric segmentation, surface area measurements were performed. The VNO was found in less than half of the studied specimens (42.2%). Neuron specific enolase and calretinin immunoexpression showed a decreasing trend with foetal age, while the other neural/neuroendocrine markers were negative in all specimens. Cytokeratin 7 expression increased with age, while Pan-Ctk had no significant variations. S100 protein immunoexpression also decreased around the VNO. The results of the present work uphold the theory of regression of the neuroepithelium that is present during initial stages of foetal development.

  8. Cell Jamming in the Airway Epithelium.

    PubMed

    Park, Jin-Ah; Fredberg, Jeffrey J

    2016-03-01

    Hallmarks of asthma include chronic airway inflammation, progressive airway remodeling, and airway hyperresponsiveness. The initiation and perpetuation of these processes are attributable at least in part to critical events within the airway epithelium, but the underlying mechanisms remain poorly understood. New evidence now suggests that epithelial cells derived from donors without asthma versus donors with asthma, even in the absence of inflammatory cells or mediators, express modes of collective migration that innately differ not only in the amount of migration but also in the kind of migration. The maturing cell layer tends to undergo a transition from a hypermobile, fluid-like, unjammed phase in which cells readily rearrange, exchange places, and flow, to a quiescent, solid-like, jammed phase in which cells become virtually frozen in place. Moreover, the unjammed phase defines a phenotype that can be perpetuated by the compressive stresses caused by bronchospasm. Importantly, in cells derived from donors with asthma versus donors without asthma, this jamming transition becomes substantially delayed, thus suggesting an immature or dysmature epithelial phenotype in asthma. PMID:27027955

  9. The management of extensive corrosive esophageal strictures: do not dilate and procrastinate.

    PubMed

    Chattopadhyay, T K; Kapoor, V K; Gupta, S

    1989-03-01

    Corrosive strictures of the esophagus are difficult to treat, however, prompt and appropriate management of corrosive burns to the esophagus can prevent the formation of strictures. In a developing country like India, where facilities for early treatment are not easily available, strictures are an inevitable consequence. If the strictures are extensive, dilatational therapy proves ineffective and offers no substantial benefit to the patients. Twenty patients with extensive corrosive strictures of the esophagus were surgically managed; by esophageal bypass in 13 and esophagectomy in 7. Surgical treatment restored normal swallowing in all the patients. The common post-operative complications to occur were: pulmonary complications, anastomotic leak and stricture, gastric outlet obstruction and reflux esophagitis. For extensive corrosive strictures of the esophagus, we advocate early surgical treatment rather than prolonged dilatational therapy.

  10. Oropharyngeal/Esophageal Candidiasis ("Thrush")

    MedlinePlus

    ... that occurs when there is overgrowth of a yeast called Candida . Candida yeasts normally live on the skin or mucous membranes ... inside the mouth or throat becomes imbalanced, the yeasts can multiply and cause symptoms. Candida overgrowth can ...

  11. Changes in the adult vertebrate auditory sensory epithelium after trauma.

    PubMed

    Oesterle, Elizabeth C

    2013-03-01

    Auditory hair cells transduce sound vibrations into membrane potential changes, ultimately leading to changes in neuronal firing and sound perception. This review provides an overview of the characteristics and repair capabilities of traumatized auditory sensory epithelium in the adult vertebrate ear. Injured mammalian auditory epithelium repairs itself by forming permanent scars but is unable to regenerate replacement hair cells. In contrast, injured non-mammalian vertebrate ear generates replacement hair cells to restore hearing functions. Non-sensory support cells within the auditory epithelium play key roles in the repair processes.

  12. [Ovarian surface epithelium and its histogenic relation to ovarian cancer].

    PubMed

    Dietl, J; Buchholz, F; Stoll, P

    1986-09-01

    Approximately 80 to 90 per cent of adult ovarian cancers are assumed to originate from ovarian surface cells. A series of morphological and biochemical studies has been recently conducted to test this. The ovarian surface epithelium shows permanent morphological changes such as crypts, inclusion cysts, villous processes and different forms of müllerian epithelium. The unique nature of ovarian surface changes and their abrupt disappearance in immediately adjacent mesothelia suggest that local factors may play an important part in modifying the growth and morphogenesis of the epithelium of the ovarian surface. Whether these endogenous and/or exogenous factors may also induce surface neoplasia is a moot point.

  13. Intracellular transport of nanocarriers across the intestinal epithelium.

    PubMed

    Fan, Weiwei; Xia, Dengning; Zhu, Quanlei; Hu, Lei; Gan, Yong

    2016-05-01

    The intestinal epithelium is the main barrier restricting the oral delivery of low-permeability drugs. Over recent years, numerous nanocarriers have been designed to improve the efficiency of oral drug delivery. However, the intracellular processes determining the transport of nanocarriers across the intestinal epithelium remain elusive, and only limited enhancement of the oral bioavailability of drugs has been achieved. Here, we review the processes involved in nanocarrier trafficking across the intestinal epithelium, including apical endocytosis, intracellular transport, and basolateral exocytosis. Understanding the complex intracellular processes of nanocarrier trafficking is particularly essential for the rational design of oral drug delivery systems. PMID:27094490

  14. Follow-up barium study after a negative water-soluble contrast examination for suspected esophageal leak: is it necessary?

    PubMed

    Sanchez, Thomas R; Holz, Grant S; Corwin, Michael T; Wood, Robert J; Wootton-Gorges, Sandra L

    2015-10-01

    The purpose of this study was to determine the value of follow-up barium esophogram in diagnosing esophageal injury or leak if the initial water-soluble contrast examination of the esophagus is normal. An institutional review board (IRB)-approved retrospective review of all pediatric patients less than 18 years old referred to the radiology department for evaluation of esophageal injury or leak was performed for a 9-year period from 2005 to 2014. The majority of patients had unexplained pneumomediastinum, chest trauma (gunshot or puncture wound), or foreign body ingestion as the reason for the referral. Forty-nine patients (age range 10 days to 17 years) underwent an initial water-soluble esophogram immediately followed by a barium esophogram. Forty-six studies were negative on both water-soluble contrast and barium studies. Two studies were both positive on the initial water-soluble contrast and subsequent barium studies. A single study showed the esophageal leak only in the water-soluble study, with the follow-up barium exam being normal. The result of this study indicates that a single-contrast water-soluble esophogram alone is sensitive in the diagnosis of esophageal injury or leak. It has a 100 % sensitivity and negative predictive value. A follow-up barium esophogram only increases the study time and radiation dose to the patient.

  15. Restoring KLF5 in esophageal squamous cell cancer cells activates the JNK pathway leading to apoptosis and reduced cell survival.

    PubMed

    Tarapore, Rohinton S; Yang, Yizeng; Katz, Jonathan P

    2013-05-01

    Esophageal cancer is the eighth most common cancer in the world and has an extremely dismal prognosis, with a 5-year survival of less than 20%. Current treatment options are limited, and thus identifying new molecular targets and pathways is critical to derive novel therapies. Worldwide, more than 90% of esophageal cancers are esophageal squamous cell cancer (ESCC). Previously, we identified that Krüppel-like factor 5 (KLF5), a key transcriptional regulator normally expressed in esophageal squamous epithelial cells, is lost in human ESCC. To examine the effects of restoring KLF5 in ESCC, we transduced the human ESCC cell lines TE7 and TE15, both of which lack KLF5 expression, with retrovirus to express KLF5 upon doxycycline induction. When KLF5 was induced, ESCC cells demonstrated increased apoptosis and decreased viability, with up-regulation of the proapoptotic factor BAX. Interestingly, c-Jun N-terminal kinase (JNK) signaling, an important upstream mediator of proapoptotic pathways including BAX, was also activated following KLF5 induction. KLF5 activation of JNK signaling was mediated by KLF5 transactivation of two key upstream regulators of the JNK pathway, ASK1 and MKK4, and inhibition of JNK blocked apoptosis and normalized cell survival following KLF5 induction. Thus, restoring KLF5 in ESCC cells promotes apoptosis and decreases cell survival in a JNK-dependent manner, providing a potential therapeutic target for human ESCC.

  16. Detection of esophageal ulcerations with technetium-99m albumin sucralfate

    SciTech Connect

    Goff, J.S.; Adcock, K.A.; Schmelter, R.

    1986-07-01

    Technetium-99m albumin-sucralfate ((/sup 99m/Tc)Su) can be used to demonstrate peptic ulcer disease in man and animals. We evaluated the usefulness of (/sup 99m/Tc)Su for detecting various grades of esophagitis. (/sup 99m/Tc)Su adhered to the distal esophagus for up to 3 hr in five of six patients with esophageal ulcers but adhered to only two of nine with lesser degrees of esophagitis. No adherence was seen in five patients without esophagitis. Thus, (/sup 99m/Tc)Su may not be useful for detecting any but the most severe grade of esophagitis. Based on these results, we speculate that the previously documented beneficial effects of sucralfate on mild to moderate esophagitis may be due to other mechanisms besides adherence to the ulcerated mucosa.

  17. Effects of irradiation on canine tracheal epithelium: a physiological and morphological correlate

    SciTech Connect

    Man, S.F.; Logus, J.W.; Mok, K.; Yamamoto, H.; Ahmed, I.H.; Man, G.C.; Hulbert, W.C.

    1987-01-01

    We delivered 20 Gy irradiation in one fraction to a 6 cm segment of trachea in 11 dogs. Tracheal mucous transport was studied before and whenever possible at weekly intervals after irradiation using a gamma camera system and /sup 99m/technetium labeled sulfur colloid. Ten of the eleven animals were sacrificed at three different time intervals (1-2, 15-16 and 30-34 weeks) post-irradiation, and the tracheal epithelium removed for studies using Ussing chambers followed by preparation for microscopic analysis. Mucous transport along the length of the trachea was normal before irradiation, but following irradiation it became abnormal in the irradiated zone. Compared to the epithelium from the cranial and caudal segments, the irradiated epithelium had similar bioelectric measurements (potential difference, short-circuit current and resistance) and mannitol permeability. Also, the changes in the bioelectric measurements following indomethacin (10(-6) M) and epinephrine (10(-6) M) used sequentially, were similar in both the control and irradiated tissues. Scanning electron microscopic analysis of the irradiated zone revealed patches of nonciliated epithelial cells among the ciliates. We conclude that irradiation caused a persistent replacement of ciliated cells with nonciliates throughout the entire study period and that this alteration impaired mucous transport but did not affect epithelial ion secretion or barrier function.

  18. DICER Regulates the Formation and Maintenance of Cell-Cell Junctions in the Mouse Seminiferous Epithelium.

    PubMed

    Korhonen, Hanna Maria; Yadav, Ram Prakash; Da Ros, Matteo; Chalmel, Frédéric; Zimmermann, Céline; Toppari, Jorma; Nef, Serge; Kotaja, Noora

    2015-12-01

    The endonuclease DICER that processes micro-RNAs and small interfering RNAs is essential for normal spermatogenesis and male fertility. We previously showed that the deletion of Dicer1 gene in postnatal spermatogonia in mice using Ngn3 promoter-driven Cre expression caused severe defects in the morphogenesis of haploid spermatid to mature spermatozoon, including problems in cell polarization and nuclear elongation. In this study, we further analyzed the same mouse model and revealed that absence of functional DICER in differentiating male germ cells induces disorganization of the cell-cell junctions in the seminiferous epithelium. We detected discontinuous and irregular apical ectoplasmic specializations between elongating spermatids and Sertoli cells. The defective anchoring of spermatids to Sertoli cells caused a premature release of spermatids into the lumen. Our findings may help also explain the abnormal elongation process of remaining spermatids because these junctions and the correct positioning of germ cells in the epithelium are critically important for the progression of spermiogenesis. Interestingly, cell adhesion-related genes were generally upregulated in Dicer1 knockout germ cells. Claudin 5 ( Cldn5 ) was among the most upregulated genes and we show that the polarized localization of CLAUDIN5 in the apical ectoplasmic specializations was lost in Dicer1 knockout spermatids. Our results suggest that DICER-dependent pathways control the formation and organization of cell-cell junctions in the seminiferous epithelium via the regulation of cell adhesion-related genes. PMID:26510868

  19. Transcription factor AP-1 in esophageal squamous cell carcinoma: Alterations in activity and expression during Human Papillomavirus infection

    PubMed Central

    2009-01-01

    Background Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir (J&K) region of India. A substantial proportion of esophageal carcinoma is associated with infection of high-risk HPV type 16 and HPV18, the oncogenic expression of which is controlled by host cell transcription factor Activator Protein-1 (AP-1). We, therefore, have investigated the role of DNA binding and expression pattern of AP-1 in esophageal cancer with or without HPV infection. Methods Seventy five histopathologically-confirmed esophageal cancer and an equal number of corresponding adjacent normal tissue biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and expression of AP-1 family of proteins by PCR, gel shift assay and immunoblotting respectively. Results A high DNA binding activity and elevated expression of AP-1 proteins were observed in esophageal cancer, which differed between HPV positive (19%) and HPV negative (81%) carcinomas. While JunB, c-Fos and Fra-1 were the major contributors to AP-1 binding activity in HPV negative cases, Fra-1 was completely absent in HPV16 positive cancers. Comparison of AP-1 family proteins demonstrated high expression of JunD and c-Fos in HPV positive tumors, but interestingly, Fra-1 expression was extremely low or nil in these tumor tissues. Conclusion Differential AP-1 binding activity and expression of its specific proteins between HPV - positive and HPV - negative cases indicate that AP-1 may play an important role during HPV-induced esophageal carcinogenesis. PMID:19758438

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

    PubMed

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

    2013-03-01

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

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

    PubMed Central

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

    2011-01-01

    The HER2 oncogene was recently reported to be amplified and overexpressed in esophageal adenocarcinoma. However, the relationship of HER2 amplification in esophageal adenocarcinoma with prognosis has not been well defined. The scoring systems for clinically evaluating HER2 in esophageal adenocarcinoma are not established. The aims of the study were to establish a HER2 scoring system and comprehensively investigate HER2 amplification and overexpression in esophageal adenocarcinoma and its precursor lesion. Using a tissue microarray, containing 116 cases of esophageal adenocarcinoma, 34 cases of BE, 18 cases of low grade dysplasia and 15 cases of high grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and CISH methods. The amplification frequency in an independent series of 116 esophageal adenocarcinoma samples was also analyzed using Affymetrix SNP 6.0 microarrays. In our studies, we have found that HER2 amplification does not associate with poor prognosis in total 232 esophageal adenocarcinoma patients by CISH and high density microarrays. We further confirm the similar frequency of HER2 amplification by CISH (18.10%; 21/116) and SNP 6.0 microarrays (16.4%, 19/116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12.1 % (14/116) of esophageal adenocarcinoma and 6.67% (1/15) of HGD. No HER2 amplification or overexpression was identified in BE or LGD. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by CISH than protein overexpression in esophageal adenocarcinoma (18.10% vs 12.9%). A modified two-step model for esophageal adenocarcinoma HER-2 testing is recommend for clinical esophageal adenocarcinoma HER-2 trial. PMID:21460800

  2. Adult-Onset Esophageal Crohn’s Disease

    PubMed Central

    Kasarala, George; Durrett, Sam

    2016-01-01

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

  3. The normal antireflux mechanism.

    PubMed

    Paterson, W G

    2001-08-01

    The normal antireflux mechanism consists of several components, any one of which may malfunction and render an individual prone to the development of GERD. The LES is clearly the most important component because gastroesophageal reflux almost always occurs when the sphincter pressure equals that of the stomach. Usually, an LES pressure of just 2 to 3 mm Hg above intragastric pressure is sufficient to prevent reflux. Other factors certainly play significant ancillary roles in preventing reflux. In the absence of a hiatal hernia, the crural fibers of the diaphragm serve as an "extrinsic" sphincter. Furthermore, the unique anatomy of the proximal stomach (e.g., the angle of His, mucosal flap valve, posterolateral location of the fundus) serves to keep gastric contents away from the gastroesophageal junction, making it less likely for reflux to occur when the LES relaxes. When a hiatal hernia is present, these factors are lost, and the hernia sac provides a reservoir for gastric juices with ready access to the LES. Finally, some degree of reflux occurs in all individuals, but esophageal clearance and acid neutralization provide an important last line of defense.

  4. Surgical treatment analysis of idiopathic esophageal achalasia

    PubMed Central

    de AQUINO, José Luis Braga; SAID, Marcelo Manzano; PEREIRA, Douglas Rizzanti; do AMARAL, Paula Casals; LIMA, Juliana Carolina Alves; LEANDRO-MERHI, Vânia Aparecida

    2015-01-01

    Background Idiopathic esophageal achalasia is an inflammatory disease of unknown origin, characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter in response to swallowing, with consequent dysphagia. Aim To demonstrate the results of surgical therapy in these patients, evaluating the occurred local and systemic complications. Methods Were studied retrospectively 32 patients, 22 of whom presented non-advanced stage of the disease (Stage I/II) and 10 with advanced disease (Stage III/IV). All of them had the clinical conditions to be submitted to surgery. The diagnoses were done by clinical, endoscopic, cardiological, radiological and esophageal manometry analysis. Pre-surgical evaluation was done with a questionnaire based on the most predisposing factors in the development of the disease and the surgical indication was based on the stage of the disease. Results The patients with non-advanced stages were submitted to cardiomyotomy with fundoplication, wherein in the post-surgical early assessment, only one (4,4%) presented pulmonary infection, but had a good outcome. In patients with advanced disease, seven were submitted to esophageal mucosectomy preserving the muscular layer, wherein one patient (14,2%) presented dehiscence of gastric cervical esophagus anastomosis as well as pulmonary infection; all of these complications were resolved with proper specific treatment; the other three patients with advanced stage were submitted to transmediastinal esophagectomy; two of them presented hydropneumothorax with good evolution, and one of them also presented fistula of the cervical esophagogastric anastomosis, but with spontaneous healing after conservative treatment and nutritional support. The two patients with fistula of the cervical anastomosis progressed to stenosis, with good results after endoscopic dilations. In the medium and long term assessment done in 23 patients, all of them reported improvement in life quality, with

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

    PubMed Central

    Sherrill, J D; KC, K; Wu, D; Djukic, Z; Caldwell, J M; Stucke, E M; Kemme, K A; Costello, M S; Mingler, M K; Blanchard, C; Collins, M H; Abonia, J P; Putnam, P E; Dellon, E S; Orlando, R C; Hogan, S P; Rothenb, M E

    2014-01-01

    The desmosomal cadherin desmoglein-1 (DSG1) is an essential intercellular adhesion molecule that is altered in various human cutaneous disorders; however, its regulation and function in allergic disease remains unexplored. Herein, we demonstrate a specific reduction in DSG1 in esophageal biopsies from patients with eosinophilic esophagitis (EoE), an emerging allergic disorder characterized by chronic inflammation within the esophageal mucosa. Further, we show that DSG1 gene silencing weakens esophageal epithelial integrity, and induces cell separation and impaired barrier function (IBF) despite high levels of desmoglein-3 (DSG3). Moreover, DSG1 deficiency induces transcriptional changes that partially overlap with the transcriptome of inflamed esophageal mucosa; notably, periostin, a multipotent pro-inflammatory extracellular matrix molecule, is the top induced overlapping gene. We further demonstrate that IBF is a pathological feature in EoE, which can be partially induced through the downregulation of DSG1 by interleukin-13 (IL-13). Taken together, these data identify a functional role for DSG1 and its dysregulation by IL-13 in the pathophysiology of EoE and suggest that the loss of DSG1 may potentiate allergic inflammation through the induction of pro-inflammatory mediators such as periostin. PMID:24220297

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

    PubMed

    Sherrill, J D; Kc, K; Wu, D; Djukic, Z; Caldwell, J M; Stucke, E M; Kemme, K A; Costello, M S; Mingler, M K; Blanchard, C; Collins, M H; Abonia, J P; Putnam, P E; Dellon, E S; Orlando, R C; Hogan, S P; Rothenberg, M E

    2014-05-01

    The desmosomal cadherin desmoglein-1 (DSG1) is an essential intercellular adhesion molecule that is altered in various human cutaneous disorders; however, its regulation and function in allergic disease remains unexplored. Herein, we demonstrate a specific reduction in DSG1 in esophageal biopsies from patients with eosinophilic esophagitis (EoE), an emerging allergic disorder characterized by chronic inflammation within the esophageal mucosa. Further, we show that DSG1 gene silencing weakens esophageal epithelial integrity, and induces cell separation and impaired barrier function (IBF) despite high levels of desmoglein-3. Moreover, DSG1 deficiency induces transcriptional changes that partially overlap with the transcriptome of inflamed esophageal mucosa; notably, periostin (POSTN), a multipotent pro-inflammatory extracellular matrix molecule, is the top induced overlapping gene. We further demonstrate that IBF is a pathological feature in EoE, which can be partially induced through the downregulation of DSG1 by interleukin-13 (IL-13). Taken together, these data identify a functional role for DSG1 and its dysregulation by IL-13 in the pathophysiology of EoE and suggest that the loss of DSG1 may potentiate allergic inflammation through the induction of pro-inflammatory mediators such as POSTN. PMID:24220297

  7. Degeneration and recovery of rat olfactory epithelium following inhalation of dibasic esters.

    PubMed

    Keenan, C M; Kelly, D P; Bogdanffy, M S

    1990-08-01

    Dibasic esters (DBE) are solvent mixtures used in the paint and coating industry. To evaluate the potential subchronic toxicity of DBE, groups of male and female rats were exposed for periods of up to 13 weeks to DBE concentrations of 0, 20, 76, or 390 mg/m3. After approximately 7 and 13 weeks of exposure, 10 rats per sex per group were subjected to clinical chemical, hematological, and urine analyses. Following 7 or 13 weeks of exposure, 10 or 20 rats per sex per group, respectively, were euthanized. An additional 10 rats were euthanized following a 6-week recovery period. A standard profile of tissues, including four levels of nasal cavity, was evaluated histopathologically. After 7 weeks of exposure, slight degeneration of the olfactory epithelium was observed in both male and female rats at 76 and 390 mg/m3. After 13 weeks, degeneration of the olfactory epithelium was present at all DBE concentrations in female rats, but only at the mid and high concentrations in male rats. The severity and incidence of the lesions were concentration related for both sexes with female rats being more sensitive than males. Following the recovery period, histological changes compatible with repair in the olfactory mucosa included an absence of degeneration, focal disorganization of the olfactory epithelium, and respiratory metaplasia. All other tissues were macroscopically normal. No other signs of toxicity were indicated by the other parameters evaluated. Inhalation studies of other esters demonstrate similar pathology in the olfactory epithelium. Since olfactory mucosa is rich in carboxylesterase activity, acids may be the toxic metabolites of these compounds. This hypothetical mechanism may explain the sensitivity of olfactory tissue to the effects of DBE.

  8. Intramural esophagic hematoma secondary to coumarinic anticoagulation: a case report

    PubMed Central

    2009-01-01

    Esophagic Intramural Hematoma is an uncommon clinical condition, with a prognosis which is essentially benign. On most cases, a predisposing or precipitating factor may be seen, with the most common ones being the history of esophagic instrumentation, food impactations and thrombocytopenia. In the following manuscript, the authors present the case of a 54-years-old male with history of valve replacement surgery, who was treated at the Clinica Cardiovascular (Medellin, Colombia), with a clinical case of Intramural Esophagic Hematoma that was later confirmed to be due to a Coumarinic overanticoagulation. On this case, it is evidenced that Intramural Esophagic Hematoma is an unrecognized complication of Courmarinic anticoagulation therapy. PMID:20069068

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

    PubMed

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

    2005-08-01

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

  10. Effect of acetic acid on optical coherence tomography (OCT) images of cervical epithelium.

    PubMed

    Gallwas, Julia; Stanchi, Anna; Dannecker, Christian; Ditsch, Nina; Mueller, Susanna; Mortensen, Uwe; Stepp, Herbert

    2014-11-01

    Optical coherence tomography (OCT) can be used as an adjunct to colposcopy in the identification of precancerous and cancerous cervical lesions. The purpose of this study was to investigate the effect of acetic acid on OCT imaging. OCT images were taken from unsuspicious and suspicious areas of fresh conization specimens immediately after resection and 3 and 10 min after application of 6 % acetic acid. A corresponding histology was obtained from all sites. The images taken 3 and 10 min after application of acetic acid were compared to the initial images with respect to changes in brightness, contrast, and scanning depth employing a standard nonparametric test of differences of proportions. Further, mean intensity backscattering curves were calculated from all OCT images in the histological groups CIN3, inflammation, or normal epithelium. Mean difference profiles within each of these groups were determined, reflecting the mean differences between the condition before application of acetic acid and the exposure times 3 and 10 min, respectively. According to the null hypothesis, the difference profiles do not differ from profiles fluctuating around zero in a stationary way, which implies that the profiles do not differ significantly from each other. The null hypothesis was tested employing the KPSS test. The visual analysis of 137 OCT images from 46 sites of 10 conization specimens revealed a statistically significant increase in brightness for all three groups and a statistically significant decrease in contrast for normal epithelium after 10 min. Further, an increase in scanning depth was noted for normal epithelium after 10 min and for CIN3 after 3 min. The analysis of mean intensity profiles showed an increased backscattering intensity after application of acetic acid. Acetic acid significantly affects the quality of OCT images. Overall brightness and scanning depth increase with the opposite effect regarding the image contrast. Whether the observed changes

  11. Expression profiles of inhibitor of growth protein 2 in normal and cancer tissues: An immunohistochemical screening analysis.

    PubMed

    Zhao, Shuang; Yang, Xue-Feng; Gou, Wen-Feng; Lu, Hang; Li, Hua; Zhu, Zhi-Tu; Sun, Hong-Zhi; Zheng, Hua-Chuan

    2016-02-01

    Inhibitor of growth protein 2 (ING2) has an important role in the regulation of chromatin remodeling, cell proliferation, cell‑cycle arrest, senescence and apoptosis. The present study performed an immunohistochemical analysis for expression profiling of ING2 protein in an array of tissues comprising normal mouse and human tissues, as well as human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung (n=192) carcinoma tissues. In mouse tissues, ING2 was detected in the nuclei and cytoplasm of the glandular epithelium of breast, hepatocytes, intestine, bronchium and alveoli, as well as the squamous epithelium of skin and glomeruli, and in myocardial cells, while it was located in the cytoplasm of renal tubules and striated muscle cells. ING2 protein was scattered in the brain and spleen. In human tissues, ING2 protein was principally distributed in the cytoplasm, while in it was present in the cytoplasm and nuclei in the stomach, intestine, cervix, endometrium trachea, breast and pancreas. The nuclear location of ING2 in the stomach was more prominent than that in the cytoplasm. High ING2 immunoreactivity was detected in the tongue, stomach, skin, pancreas, cervix and breast, whereas weakly in the brain stem, thymus, thyroid, lung, striated muscle, testis, bladder and ovary. In total, 617 out of 1,194 of the tested cancer tissues (51.7%) were ING2-positive. In most cases, ING2 expression was found to be restricted to the cytoplasm of all cancer tissues, while in certain cancer types, including renal clear cell, ovarian and colorectal carcinoma, it was occasionally present in the nuclei. Among the cancer tissues examined, ING2 was most frequently expressed in breast cancer (67.4%) and gynecological cancer types, including ovarian cancer (61.5%) and endometrial cancer (57.3%). Compared with

  12. Expression profiles of inhibitor of growth protein 2 in normal and cancer tissues: An immunohistochemical screening analysis.

    PubMed

    Zhao, Shuang; Yang, Xue-Feng; Gou, Wen-Feng; Lu, Hang; Li, Hua; Zhu, Zhi-Tu; Sun, Hong-Zhi; Zheng, Hua-Chuan

    2016-02-01

    Inhibitor of growth protein 2 (ING2) has an important role in the regulation of chromatin remodeling, cell proliferation, cell‑cycle arrest, senescence and apoptosis. The present study performed an immunohistochemical analysis for expression profiling of ING2 protein in an array of tissues comprising normal mouse and human tissues, as well as human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung (n=192) carcinoma tissues. In mouse tissues, ING2 was detected in the nuclei and cytoplasm of the glandular epithelium of breast, hepatocytes, intestine, bronchium and alveoli, as well as the squamous epithelium of skin and glomeruli, and in myocardial cells, while it was located in the cytoplasm of renal tubules and striated muscle cells. ING2 protein was scattered in the brain and spleen. In human tissues, ING2 protein was principally distributed in the cytoplasm, while in it was present in the cytoplasm and nuclei in the stomach, intestine, cervix, endometrium trachea, breast and pancreas. The nuclear location of ING2 in the stomach was more prominent than that in the cytoplasm. High ING2 immunoreactivity was detected in the tongue, stomach, skin, pancreas, cervix and breast, whereas weakly in the brain stem, thymus, thyroid, lung, striated muscle, testis, bladder and ovary. In total, 617 out of 1,194 of the tested cancer tissues (51.7%) were ING2-positive. In most cases, ING2 expression was found to be restricted to the cytoplasm of all cancer tissues, while in certain cancer types, including renal clear cell, ovarian and colorectal carcinoma, it was occasionally present in the nuclei. Among the cancer tissues examined, ING2 was most frequently expressed in breast cancer (67.4%) and gynecological cancer types, including ovarian cancer (61.5%) and endometrial cancer (57.3%). Compared with

  13. Peroral endoscopic myotomy for esophageal achalasia

    PubMed Central

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

    2014-01-01

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

  14. Spontaneous enterogastric reflux gastritis and esophagitis.

    PubMed Central

    Gowen, G F

    1985-01-01

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

  15. Parenteral nutrition in esophageal cancer patients.

    PubMed Central

    Daly, J M; Massar, E; Giacco, G; Frazier, O H; Mountain, C F; Dudrick, S J; Copeland, E M

    1982-01-01

    A review of operative therapy in 244 patients with esophageal cancer from 1960 to 1980 was done to evaluate the impact of TPN in 72 patients treated from 1973 to 1980 with 43 non-TPN patients treated during the same period and to 129 patients operated upon before 1973. Mean age, sex distribution, site, stage, and treatment of the disease were similar for the two study groups. The TPN group lost less weight during treatment (3 lbs vs. 11 lbs) and had fewer overall complications postoperatively (24% vs. 41%). Significant reductions in major wound, infectious, and postoperative complications were noted in these patients who received at least 5 days of preoperative TPN compared with postoperative TPN or the non-TPN groups (4% vs. 24% and 23%). Malnourished esophageal cancer patients can more safely undergo aggressive operative therapy and radiation treatment when adequate perioperative nutritional support is added to the treatment armamentarium. PMID:6807225

  16. Difficult esophageal atresia: trick and treat.

    PubMed

    Conforti, Andrea; Morini, Francesco; Bagolan, Pietro

    2014-10-01

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

  17. Early esophageal cancer screening in China.

    PubMed

    Gao, Qin-Yan; Fang, Jing-Yuan

    2015-12-01

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

  18. Early esophageal cancer screening in China.

    PubMed

    Gao, Qin-Yan; Fang, Jing-Yuan

    2015-12-01

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

  19. Esophageal Dose Tolerance to Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors for Late Toxicity

    SciTech Connect

    Stephans, Kevin L.; Djemil, Toufik; Diaconu, Claudiu; Reddy, Chandana A.; Xia, Ping; Woody, Neil M.; Greskovich, John; Makkar, Vinit; Videtic, Gregory M.M.

    2014-09-01

    Purpose: To identify factors associated with grade ≥3 treatment related late esophageal toxicity after lung or liver stereotactic body radiation therapy (SBRT). Methods and Materials: This was a retrospective review of 52 patients with a planning target volume within 2 cm of the esophagus from a prospective registry of 607 lung and liver SBRT patients treated between 2005 and 2011. Patients were treated using a risk-adapted dose regimen to a median dose of 50 Gy in 5 fractions (range, 37.5-60 Gy in 3-10 fractions). Normal structures were contoured using Radiation Therapy Oncology Group (RTOG) defined criteria. Results: The median esophageal point dose and 1-cc dose were 32.3 Gy (range, 8.9-55.4 Gy) and 24.0 Gy (range, 7.8-50.9 Gy), respectively. Two patients had an esophageal fistula at a median of 8.4 months after SBRT, with maximum esophageal point doses of 51.5 and 52 Gy, and 1-cc doses of 48.1 and 50 Gy, respectively. These point and 1-cc doses were exceeded by 9 and 2 patients, respectively, without a fistula. The risk of a fistula for point doses exceeding 40, 45, and 50 Gy was 9.5% (n=2/21), 10.5% (n=2/19), and 12.5% (n=2/16), respectively. The risk of fistula for 1-cc doses exceeding 40, 45, and 50 Gy was 25% (n=2/9), 50% (n=2/4), and 50% (n=2/4), respectively. Eighteen patients received systemic therapy after SBRT (11 systemic chemotherapy, and 6 biologic agents, and 1 both). Both patients with fistulas had received adjuvant anti-angiogenic (vascular endothelial growth factor) agents within 2 months of completing SBRT. No patient had a fistula in the absence of adjuvant VEGF-modulating agents. Conclusions: Esophageal fistula is a rare complication of SBRT. In this series, fistula was seen with esophageal point doses exceeding 51 Gy and 1-cc doses greater than 48 Gy. Notably, however, fistula was seen only in those patients who also received adjuvant VEGF-modulating agents after SBRT. The potential interaction of dose and adjuvant therapy

  20. Advances in Clinical Management of Eosinophilic Esophagitis

    PubMed Central

    Dellon, Evan S.; Liacouras, Chris A.

    2014-01-01

    EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines—EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885