Background Barrett's esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes a transdifferentiation program resulting in a simple columnar epithelium reminiscent of the small intestine. These changes are typically associated with the stratified squamous epithelium chronically exposed to acid and bile salts as a result of gastroesophageal reflux disease (GERD). Despite this well-defined epidemiologic association between acid reflux and Barrett's esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocytes have remained undefined. Methodology/Principal Findings To begin to identify the genetic changes responsible for transdifferentiaiton in Barrett's esophagus, we performed a microarray analysis of normal esophageal, Barrett's esophagus and small intestinal biopsy specimens to identify candidate signaling pathways and transcription factors that may be involved. Through this screen we identified the Cdx1 homeodomain transcription factor and the c-myc pathway as possible candidates. Cdx1 and c-myc were then tested for their ability to induce transdifferentiation in immortalized human esophageal keratinocytes using organotypic culturing methods. Analyses of these cultures reveal that c-myc and cdx1 cooperate to induce mucin production and changes in keratin expression that are observed in the epithelium of Barrett's esophagus. Conclusions/Significance These data demonstrate the ability of Cdx1 and c-myc to initiate the earliest stages of transdifferentiation of esophageal keratinocytes toward a cell fate characteristic of Barrett's esophagus.
Stairs, Douglas B.; Nakagawa, Hiroshi; Klein-Szanto, Andres; Mitchell, Shukriyyah D.; Silberg, Debra G.; Tobias, John W.; Lynch, John P.; Rustgi, Anil K.
OBJECTIVES:The development of reflux esophagitis in humans is a process resulting from esophageal exposure to refluxed gastric contents. There is no doubt that damage to the esophageal epithelium requires exposure to gastric acid; however, the role of refluxed pepsin as contributor to this damage seems to be underappreciated.METHODS:The role of physiological concentrations of pepsin was examined in Ussing chambered rabbit
Nelia A. Tobey; S. Seraj Hosseini; Canan Caymaz-Bor; Holly R. Wyatt; Geraldine S. Orlando; Roy C. Orlando
This article focusses on the structural development of human esophageal ciliated epithelium. A combination of transmission electron microscopic (TEM), scanning electron microscopic (SEM), radioautographic, and light microscopic (LM) analyses were carried out using intact fetal tissues between 8 and 20 weeks of gestation as well as cultured esophageal explants. Up to the age of 10 weeks, the stratified esophageal epithelium consisted of two longitudinal primary folds. The surface cells were undifferentiated and contained large glycogen aggregates. Between 11 and 16 weeks, the primary folds (now up to four) had developed secondary folds. The thickness of the epithelium drastically increased (123%) in concomittance with a differentiation of surface columnar ciliated cells. These highly specialized surface cells exhibited junctional complexes and well-developed organelles with numerous microvilli interspersed among the cilia. Transverse sections revealed the internal structure of the cilia with a consistent pattern of nine doublet microtubules surrounding a central pair of single microtubules. Freeze-fracture studies illustrated the presence of a ciliary necklace composed of 6 ring-like rows of intramembranous particles. They also revealed the structure of ciliary cell tight junctions consisting of up to nine anastomosing strands (P-face) or complementary grooves (E-face). Ultrastructural studies (LM, TEM, SEM) of the esophageal squamous epithelium obtained after 15 days of culture showed that the newly formed epithelium was similar to adult human epithelium. Finally LM and SEM observations established that the esophagogastric junction was not yet well delineated, consisting of a transitional area composed of a mixture of esophageal ciliated cells and gastric columnar mucous cells. PMID:7670160
Hot beverages expose the esophageal epithelium to temperatures as high as 58 degrees C. To study the impact of such temperatures, rabbit esophageal epithelium was exposed to luminal heat or both luminal and serosal heat while mounted in Ussing chambers. Luminal heat, mimicking exposure to hot beverages, reduced potential difference (PD) and resistance (R) when applied at >/=49 degrees C and reduced short-circuit current (Isc) at >/=60 degrees C. At >/=60 degrees C, subepithelial blisters developed. Higher temperatures reduced R only moderately and reversibly. In contrast, the Isc declined sharply and irreversibly once threshold was reached. Luminal and serosal heat also reduced PD, Isc, and R, although the threshold for reduction in Isc was now similar to that for R. Additionally, luminal and serosal heat reduced Isc more than R for any given temperature and resulted in blisters at lower temperatures (50 degrees C) than luminal heat alone. The heat-induced decline in Isc was attributed in part to inactivation of Na-K-ATPase activity, although other transport systems could have been equally affected, and the decline in R to an increase in paracellular permeability. The latter effect on R also contributed to an increase in tissue sensitivity to luminal acid damage. Consumption of hot beverages exposes the esophagus to temperatures that can negatively impact epithelial structure and function. Impaired barrier function by heat increases the risk of esophageal damage by subsequent contact with (refluxed) gastric acid. These findings help explain in part the association between esophageal disease and consumption of hot beverages. PMID:10362635
Tobey, N A; Sikka, D; Marten, E; Caymaz-Bor, C; Hosseini, S S; Orlando, R C
OBJECTIVES:It has recently been established that patients with nonerosive reflux disease have on biopsy within esophageal epithelium a lesion known as dilated intercellular spaces (DIS).METHODS:To further explore the nature and implications of this lesion, in vitro models of nonerosive acid and acid-pepsin damage were created in Ussing chamber-mounted rabbit esophageal epithelium. Using these models circuit analysis and permeability studies were
NA Tobey; SS Hosseini; CM Argote; AM Dobrucali; Awayda; RC Orlando
Some patients referred for esophagogastroduodenoscopy (EGD) to evaluate symptoms of dysphagia have normal endoscopies. How best to manage these patients is unclear. We reviewed our experience with empiric esophageal dilation in this setting. Over a five-year period, 40 consecutive patients with esophageal dysphagia and normal EGD underwent empiric esophageal dilation at the time of their endoscopy. Postdilation follow-up was available
John B. Marshall; Tabassum A. Chowdhury
Background/Aims: The study examines the relationship between activity of acid DNase and 5'nucleotidase (5'NT) and histological changes in reflux esophagitis. Methodology: Thirty-three patients were examined, 15 of whom with mild esophagitis, 12 with severe esophagitis and 6 with Barrett's epithelium. Patients were classified into 3 groups, according to Ismail-Beigi histological criteria: mild esophagitis group (ME); severe esophagitis group (SE); Barrett's esophagitis group (BE). DNase and 5'NT levels were measured biochemically both in healthy and injured tissue samples. Results: Difference of acid DNase and 5'NT activity in healthy tissue versus injured tissue samples was the lowest in ME group: 0.55±4.47 U/g for acid DNase and 11.56±37.11 U/g for 5'NT, the difference increased to 4.43±1.64 U/g for acid DNase and 105.57±54.11 U/g for 5'NT in the SE group, while 6.07±2.92 U/g for acid DNase and 109.83±14.02 U/g for 5'NT as the highest levels were measured in the BE group. Difference in BE group is statistically significantly higher (p <0.05) compared to the ME group, confirmed by ANOVA with Dunnett's post hoc test. Conclusions: The study shows significant decrease of apotosis level that is detectable even before metaplasia was morphologically defined. PMID:23803371
Radisavljevic, Mirjana M; Nagorni, Aleksandar V; Kocic, Gordana; Bjelakovic, Goran B; Petrovic, Aleksandar S; Veljkovic, Andrej R; Raicevic-Sibinovic, Suzana R; Radisavljevic, Misa M
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 ?m from the surface and disappeared at a depth of approximately 300 ?m. 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 ?m 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. PMID:23617670
Omae, Masami; Fujisaki, Junko; Shimizu, Tomoki; Igarashi, Masahiro; Yamamoto, Noriko
The ovarian steroids estrogen and progesterone (E2 and P) are essential for normal mammary gland growth and development; however, the mechanisms by which they influence the proliferative activity of the mammary epithelium remain unclear. Mammary epithelial cells cells expressing the receptors for E2 and P (ER and PR respectively) are separate from, although often adjacent to, those capable of proliferating,
Elizabeth Anderson; Robert B. Clarke
The second part of our study deals with a comparative evaluation and discussion of the immunohistochemical results that were obtained. The cryoscanning electron microscopy (cryoSEM) observations confirmed a monolayer colonization of the esophageal surface with bacteria and fungi (yeasts); the latter in particular was prominent in the ruminant species studied. We demonstrated the existence of several innate immune parameters, including pathogen recognition receptors (PRRs), such as Toll-like receptor 2, which was primarily expressed in the stratum basale; however, the presence ?-glucan receptors remained inconclusive. Furthermore, the group of cationic antimicrobial peptides (CAPs) was shown, comprising ?-defensins 2 and 3 and cathelicidin. The less keratinized esophageal epithelium of the carnivorous cat was protected by high amounts of CAPs; whereas the more strongly keratinized epithelium of the herbivorous and omnivorous species with its characteristic layer structure exhibited clearly weaker reactions. Moreover, lysozyme could distinctly be demonstrated in the cells of the esophageal epithelium. It can be concluded that a first line of defence mechanisms of the innate immune system contributes to maintaining a microbial homeostasis on the surface of the esophageal epithelium of domesticated mammals. The results are discussed in comparison to findings from studies on the human esophagus. PMID:20022082
Nina Hornickel, Isabelle; Kacza, Johannes; Schnapper, Anke; Beyerbach, Martin; Schoennagel, Britta; Seeger, Johannes; Meyer, Wilfried
The multiple roles of both estrogenic and polypeptide regulators of mammary epithelial cell growth are reviewed in this article. Effects of both steroidal and peptide hormones are complex and involve multiple interactions with malignant cells and non-malignant host components. Initial carcinogenesis and progression of mammary epithelium to cancer probably require both proliferative stimuli (estrogen, polypeptide growth factors) and genetic damage. This condition may lead to qualitatively different hormonal responses (hormone-responsive cancer). Estrogens can be shown to induce growth-regulatory polypeptide growth factors and interact with them in hormone-dependent breast cancer. Progression of hormone-dependent (estrogen-responsive) breast cancer to hormone independence probably involves multiple mechanisms, including oncogene activation, loss of the estrogen receptor, or loss of hormone responsivity of other gene products. One direction for further therapies may be blockade of hormonal stimulation and interference with necessary activated or induced components of malignant progression such as oncogenes or polypeptide growth factor-receptor systems.
Lippman, M. E.; Dickson, R. B.
Two normal senile lens epithelia obtained from keratoplastic donor eyes were cultured using Francois’ plasma cloth method. With cell samples taken from the equatorial region it was possible to estimate all stages of mitosis.
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
Wilson, J A; Mainie, I; Tutuian, R; Agrawal, A; Castell, D O
Abstract Abstract Abstract Abstract AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonucleotide microarray. METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P
Chuan-Ding Yu; Shen-Hua Xu; Hang-Zhou Mou; Zhi-Ming Jiang; Chi-Hong Zhu; Xiang-Lin Liu
From a case illustrated, it appears that irradiation may induce changes in normal breast epithelium indistinguishable from malignancy by means of aspiration cytology. This fact must be considered in the choice of diagnostic methods for the evaluation of lesions in irradiated breast tissue.
Scintigraphic technique was used to study esophageal transport of a solid bolus in 16 patients with dysphagia but with normal manometry, and negative acid perfusion tests, acid clearing tests, and pH reflux tests. Radiology performed on 14 of the 16 patients showed no evidence of organic lesions. Half the patients had abnormal findings at scintigraphy, with either bolus retention in
Gerhard Kjellén; John B. Svedberg; Lita Tibbling
Four patients with herpetic esophagitis were examined. In three of them, the presenting symptom was odynophagia. Early in the course of herpetic esophagitis, shallow round and oval ulcers were seen on barium esophagograms. Later, the ulcers filled with fibrinous exudate, forming nodular plaques that projected into the esophageal lumen. Although these findings are diagnostic of esophagitis, they are not specific for a herpes virus infection. The definitive diagnosis must be established by histologic examination, which demonstrates the cytopathic effect of the herpes virus infection within the squamous epithelium.
Shortsleeve, M.J.; Gauvin, G.P.; Gardner, R.C.; Greenberg, M.S.
With the aid of high-speed cineradiography the pharyngeal stage of deglutition was examined among 150 volunteers without dysphagia in order to evaluate the radiographic pattern of normal deglutition. In order to evaluate the diagnostic result of cineradio...
The present study sought to determine whether estrogens with testosterone support are sufficient to transform the normal human prostate epithelium and promote progression to invasive adenocarcinoma using a novel chimeric prostate model. Adult prostate stem/early progenitor cells were isolated from normal human prostates through prostasphere formation in three-dimensional culture. The stem/early progenitor cell status and clonality of prostasphere cells was confirmed by immunocytochemistry and Hoechst staining. Normal prostate progenitor cells were found to express estrogen receptor ?, estrogen receptor ?, and G protein-coupled receptor 30 mRNA and protein and were responsive to 1 nm estradiol-17? with increased numbers and prostasphere size, implicating them as direct estrogen targets. Recombinants of human prostate progenitor cells with rat urogenital sinus mesenchyme formed chimeric prostate tissue in vivo under the renal capsule of nude mice. Cytodifferentiation of human prostate progenitor cells in chimeric tissues was confirmed by immunohistochemistry using epithelial cell markers (p63, cytokeratin 8/18, and androgen receptor), whereas human origin and functional differentiation were confirmed by expression of human nuclear antigen and prostate-specific antigen, respectively. Once mature tissues formed, the hosts were exposed to elevated testosterone and estradiol-17? for 1–4 months, and prostate pathology was longitudinally monitored. Induction of prostate cancer in the human stem/progenitor cell-generated prostatic tissue was observed over time, progressing from normal histology to epithelial hyperplasia, prostate intraepithelial neoplasia, and prostate cancer with local renal invasion. These findings provide the first direct evidence that human prostate progenitor cells are estrogen targets and that estradiol in an androgen-supported milieu is a carcinogen for human prostate epithelium.
Hu, Wen-Yang; Shi, Guang-Bin; Lam, Hung-Ming; Hu, Dan-Ping; Ho, Shuk-Mei; Madueke, Ikenna C.; Kajdacsy-Balla, Andre
Bronchial epithelial dysplasia is thought to be a premalignant stage in the evolution of lung cancers. Using the CM-1 polyclonal antibody, we have examined the expression of the p53 protein in a larger series of bronchial dysplasias (n = 60) than hitherto investigated. The p53 protein was detected in 14% of mild, 25% of moderate and 59% of severe dysplasias; increased p53 expression correlated with the severity of dysplasia. p53-positive dysplasias had greater PCNA indices than p53-negative dysplasias. p53 expression in dysplastic tissues was compared with that in two groups of histologically normal epithelium: 14 bronchial biopsies from non-cancer patients of which all but one were negative and 32 bronchial margins from resected carcinomas, of which 17 showed infrequent solitary cells with p53-positive nuclei in predominantly basal locations scattered throughout the epithelium. These results for resection margins were confirmed by use of a second antibody, DO-1. Sixty-nine per cent of the corresponding carcinomas were p53 positive, but in 15 cases the p53 reactivity differed from resection margins. No correlation between p53 expression and any of the clinicopathological characteristics of these tumours was found. This study supports the observation that abnormal p53 expression may be an early but not obligatory event in malignant transformation in lung. Images Figure 1 Figure 2
Walker, C.; Robertson, L. J.; Myskow, M. W.; Pendleton, N.; Dixon, G. R.
The aim of the investigation was to demonstrate that the esophageal epithelium of domesticated mammals exhibits characteristic features of innate immunity. The esophageal samples used were obtained immediately after euthanization from seven species of domesticated mammals of three nutrition groups (herbivores: horse, goat, cattle; omnivores: pig, dog, laboratory rat; carnivores: cat). The experimental basis was immunohistochemistry, which was evaluated in a qualitative and statistically relevant semi-quantitative manner. The first part of the study analyzed the influence of different fixation media on the immunohistochemical reactivities. Two formalin-based routine fixation solutions (Bouin's solution, Ca-acetate formalin) were compared with the recently introduced formalin-free HOPE® fixative. In this context, we clearly demonstrated a diminished immunoreactivity for Ca-formol fixed samples; satisfactory results were obtained, particularly, from samples fixed in Bouin's solution. The HOPE® fixation method offers a relatively cheap alternative, as the antibody amounts can be reduced. An application in routine diagnostic is not advisable, because of several variable parameters. It can be concluded that immunohistochemical results have always to be evaluated and discussed in close relation to the fixation medium used. PMID:19850328
Nina Hornickel, Isabelle; Kacza, Johannes; Schnapper, Anke; Beyerbach, Martin; Schoennagel, Britta; Seeger, Johannes; Meyer, Wilfried
Growth factors are important in healing and restoration of injured gastrointestinal tissues and, therefore, we characterised temporally the distribution and density of epidermal growth factor receptor (EGFr) in normal and peptic-injured gastric squamous epithelium of horses. Lesions were induced in the equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Fifteen mature horses, 9 geldings and 6 mares, age 3 to 20 years, were used and divided into 3 groups: Group 1 (n = 5) were subjected to euthanasia for problems unrelated to the gastrointestinal tract and had normal-appearing gastric squamous mucosal epithelium; Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for a total of 48 h and 96 h, respectively. Following lethal injection of a barbiturate, stomachs were removed and fixed by filling with 4- 6 l 10% buffered formalin. Sections were made from normal stomachs and lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. A modified avidin-biotin immunoperoxidase technique was used to stain the formalin-fixed tissue specimens for EGFr. A computerised image analysis system was used to measure area occupied by EGFr (EGFr area) and mean EGFr density in 4 zones within the epithelium extending from the basal cell layers toward the lumen. Measurements were made of epithelium in an erosion bed, at the margin of an ulcer or erosion, and 10-15 mm distant from the lesion margin. Additionally, EGFr area and density were measured in epithelial cells adjacent to capillaries in the epithelium. Intermittent feed deprivation resulted in erosion and ulceration of the gastric squamous epithelium of each horse. Mean EGFr area and density were greatest (P<0.05) in the basal layer of epithelia from all horses, and EGFr staining diminished progressively toward the lumen. Tissues from Group 3 had significantly greater EGFr area in the lesion margin than epithelia from Group 2. EGFr density was less in the epithelia of erosion beds from Groups 2 and 3 compared to normal epithelium, and EGFr area in Group 2 erosion bed epithelia was significantly less than in normal epithelium and epithelia of Group 3. EGFr area in cells adjacent to epithelial capillaries of Group 3 was significantly greater than that of Group 1. Mitotic cell activity was significantly greater in epithelia associated with ulcers and erosions in Groups 2 and 3 compared to normal tissues from Group 1 horses. Staining for EGFr in the glandular mucosa adjacent to squamous epithelium at the margo plicatus was inconsistent and typically faint when present. EGFr distribution in equine gastric squamous epithelium was greatest in regions of greatest cell proliferation, and these areas were in the basal layers of epithelium and immediately adjacent to capillaries. There was evidence that EGFr is induced in peptic-injured equine gastric squamous epithelium. A receptor ligand, EGF or transforming growth factoralpha, may be a factor in healing of gastric squamous mucosal ulcers in horses. Further research should be directed at identifying this ligand and determining its origin in equine gastric mucosa. PMID:11720027
Jeffrey, S C; Murray, M J; Eichorn, E S
Forty-nine biopsies of bulbar conjunctiva from patients with no apparent conjunctival disease were studied by light and transmission electron microscopy. No significant morphological changes were recorded in those specimens from patients less than 79 years old. However, in the older age group the epithelium showed irregularities in thickness, a reduction in the goblet cell population, and in 25% the presence of 'hyaline bodies'. The epithelial irregularities consisted of mild superficial stratification, which was observed also in a few of the specimens from the younger age groups. The goblet cells appeared morphologically normal in all age groups. The significance of the hyaline bodies and their possible relationship to goblet cells is discussed. Images
Abdel-Khalek, L. M.; Williamson, J.; Lee, W. R.
The goal of this study is to determine whether the occurrence of AI/LOH in the DNA of histologically normal epithelium from noncancerous breasts predicts future breast cancer development. If so, then AI/LOH would be an excellent candidate molecular marker...
C. L. Rosenberg
Rapid pull-through pressure profiles of the normal human upper esophageal sphincter (UES) were simultaneously studied with a conventional three-orifice Honeywell solid-state probe, an eight lumen radially perfused (RP) probe, and a circumferentially sensitive (CS) probe designed to measure UES pressure (UESP) without regard to probe orientation. Pressure curves were digitized and analyzed by computer. The Honeywell probe recorded significantly lower peak pressures than the other two methods, and had wide intrasubject pressure variations (average coefficient of variation, 53%). In contrast, UESP measured with the CS probe was constant for each subject (mean peak UESP, 121 mm Hg; average coefficient of variation, 15%). Anteroposterior RP probe UESP were identical to CS probe pressures. Thus, peak perfused anteroposterior UESP correlates with circumferentially measured sphincter squeeze. Computer programs were written that allowed RP probe pressures to be mapped in three dimensions. Normal three-dimensional maps were characterized by anteroposterior accentuation of peak pressures and also by consistent axial asymmetry with anterior peak pressures occurring 0.8±0.2 cm closer to the pharynx. After defining the normal two- and three-dimensional UESP configuration, patients who had undergone laryngectomy were studied. Peak pressures measured with the RP probe decreased to ?50 mm Hg and radial pressure asymmetry vanished. Like normals, CS probe pressures corresponded to peak RP probe pressures. UES length did not change significantly. Three-dimensional mapping showed that axial asymmetry also vanished. It therefore appears that the anatomic alterations produced by laryngectomy abolishes UESP asymmetry. Images
Welch, Richard W.; Luckmann, Kenneth; Ricks, Phillip M.; Drake, Samuel T.; Gates, George A.
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-1? 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-1? and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1? and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1? and TNF?. 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.
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.
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-1? 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-1? and IL-18 production. In whole lung, inRNA expression of NAIP and procaspase-1 was increased in OVA mice, whereas NLRP3, IL-1? and IL-18 decreased. Some OVA-treated mice also had significantly elevated and tightly correlated serum levels of IL-1? and TNF?. 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
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
The radioactive microsphere technique was used to estimate blood flow to different regions of the esophagus and to adjacent regions of the stomach before and after perfusion of the esophagus with hydrochloric acid (pH 1.5) for 5 min. Under resting conditions total blood flow, as well as blood flow to the mucosal-submucosal layer and the muscular layer, to both sphincters was significantly higher than to the esophageal body. Blood flow to the adjacent regions of the stomach was significantly higher than esophageal blood flow. Acid perfusion resulted in a large increase in total blood flow in both sphincters and the lower esophageal body. Gastric blood flow was not altered by acid perfusion. The esophageal hyperemia resulted primarily from an increase in blood flow to the muscular layer; mucosal-submucosal blood flow was increased only in the lower esophageal sphincter. The present study indicates that short periods (5 min) of gastroesophageal reflux may increase esophageal blood flow.
Hollwarth, M.E.; Smith, M.; Kvietys, P.R.; Granger, D.N.
Rapid pull-through pressure profiles of the normal human upper esophageal sphincter (UES) were simultaneously studied with a conventional three-orifice Honeywell solid-state probe, an eight lumen radially perfused (RP) probe, and a circumferentially sensitive (CS) probe designed to measure UES pressure (UESP) without regard to probe orientation. Pressure curves were digitized and analyzed by computer. The Honeywell probe recorded significantly lower peak pressures than the other two methods, and had wide intrasubject pressure variations (average coefficient of variation, 53%). In contrast, UESP measured with the CS probe was constant for each subject (mean peak UESP, 121 mm Hg; average coefficient of variation, 15%). Anteroposterior RP probe UESP were identical to CS probe pressures. Thus, peak perfused anteroposterior UESP correlates with circumferentially measured sphincter squeeze.Computer programs were written that allowed RP probe pressures to be mapped in three dimensions. Normal three-dimensional maps were characterized by anteroposterior accentuation of peak pressures and also by consistent axial asymmetry with anterior peak pressures occurring 0.8+/-0.2 cm closer to the pharynx. After defining the normal two- and three-dimensional UESP configuration, patients who had undergone laryngectomy were studied. Peak pressures measured with the RP probe decreased to congruent with50 mm Hg and radial pressure asymmetry vanished. Like normals, CS probe pressures corresponded to peak RP probe pressures. UES length did not change significantly. Three-dimensional mapping showed that axial asymmetry also vanished. It therefore appears that the anatomic alterations produced by laryngectomy abolishes UESP asymmetry. PMID:447825
Welch, R W; Luckmann, K; Ricks, P M; Drake, S T; Gates, G A
The present study was designed to determine whether increased vascularity occurs during malignant transformation of human oral cheek epithelium. Nine normal (N) samples were taken from the resection margins of benign lesions; the pathological lesions were classified as chronic inflammation (CI; n=11), fibrous hyperplasia (FH; n=12), lichen planus (LIP; n=8), dysplasia (DYS; n=5), squamous cell carcinoma (SCC; n=25; well differentiated
G. L. Tipoe; F. H. White; Y. Jin; L. Yang
Summary The purpose of our study was to evaluate the correlation between cyclooxygenase-2 (COX-2) and aromatase immunohistochemical\\u000a expression in ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) present in the same breast, as well as in adjacent stroma and normal epithelium,\\u000a we still correlated with nuclear grade, histologic grade, presence or absence of comedonecrosis, tumor size, and age at
Vilmar Marques Oliveira; Sebastião Piato; Maria Antonieta Longo Galvão Silva
H19, a paternally imprinted gene, is postulated to have regulatory functions in normal development and oncogenesis. Loss of imprinting (LOI) of H19 is observed in human malignancies, including lung cancer. Microarray assessment of gene expression patterns in airway epithelium of healthy 20 pack-year smokers versus nonsmokers revealed that smokers have dramatically elevated H19 RNA levels without alteration of expres- sion
Rana Kaplan; Karsta Luettich; Adriana Heguy; Neil R. Hackett; Ben-Gary Harvey; Ronald G. Crystal
To treat Barrett's esophagus (BE), radiofrequency ablation or cryotherapy are effective treatments for eradicating BE with dysplasia and intestinal metaplasia, and reduce the rates of Barrett's esophageal adenocarcinoma (BAC). However, patients with BE and dysplasia or early cancer who achieved complete eradication of intestinal metaplasia, BE recurred in 5% within a year, requiring expensive endoscopic surveillances. We performed endoscopic submucosal dissection as complete radically curable treatment procedure for BE with dysplasia, intestinal metaplasia and BAC. PMID:23964158
Mori, Hirohito; Kobara, Hideki; Rafiq, Kazi; Nishiyama, Noriko; Fujihara, Shintaro; Ayagi, Maki; Yachida, Tatsuo; Kato, Kiyohito; Masaki, Tsutomu
Two roles have been suggested for basal cells on the basis of studies performed with laboratory ani- mals: ( 1 ) anchoring of the tracheobronchial epithelium; and ( 2 ) being the epithelial stem cell. Para- basal cells located just above the basal cells have also been shown to contribute to cell renewal. How- ever, a systematic study of the
JAMES E. BOERS; ANTON W. AMBERGEN; FREDERIK B. J. M. THUNNISSEN
The present study attempted to investigate if alaryngeal speakers of Mandarin Chinese could differentially produce the four tone levels of Mandarin: high-level, mid-rising, falling-rising and high-falling, as perceived by native listeners. Syllables /ma/ and /ba/ produced at four different tone levels by 8 normal laryngeal (NL), 7 standard esophageal (SE), and 8 electrolaryngeal (EL) speakers of Mandarin were perceived by 8 naïve listeners. Results from the listening experiments showed a higher percent correct identification of tone for NL speech than SE and EL speech. Perceptual data showed different patterns of tone confusion associated with the three types of speech. SE and EL speakers were not able to produce the four tone levels as accurately as were NL speakers. NL speakers achieved a near-perfect level of accuracy in signaling tonal contrasts. SE speakers produced the falling-rising and high-falling tones more accurately than high-level and mid-rising tones, but tonal confusions existed between mid-rising tone and falling-rising tone, and between high-level tone and high-falling tone. In EL phonation, high-level tone was produced more accurately than the other tones which were often misidentified as a high-level tone. PMID:16966835
Liu, Hanjun; Wan, Mingxi; Ng, Manwa L; Wang, Supin; Lu, Chunmei
The charts of 83 children with chest pain who underwent esophageal manometry followed by esophagogastroscopy were reviewed. Forty-seven (57%) had normal esophageal histology and normal motility (group I). Esophagitis and normal motility were demonstrated in 15 children (group II), normal esophageal histology and esophageal dysmotility in 13 (group III), and both esophagitis and abnormal motility in 8 (group IV). Diffuse
Mark S. Glassman; Marvin S. Medow; Stuart Berezin; Leonard J. Newman
Urokinase-type (uPA) and tissue-type (tPA) plasminogen activators were identified by fibrinolytic autography in the sulcus epithelium of human gingival mucosa but not in the orthokeratinized gingival epithelium. Fibrinolytic activity was present only over blood vessels in frozen sections of oral squamous cell carcinomas, the malignant epithelial cells showing no plasminogen activator activity. Plasminogen activators could not be demonstrated in either the sulcus or gingival epithelium by immunofluorescence, but both uPA and tPA were found in occasional squamous carcinoma cells. Fibrinolytic activity of culture fluids from epithelial explants grown in vitro from human gingival mucosa showed marked variation, but activity was much higher in the culture supernatants than in the cell lysates. Fibrinolytic activity of culture fluids from epithelial explants of squamous cell carcinomas was low both in supernatants and lysates. Zymogram overlays of sodium dodecyl sulphate-polyacrylamide electrophoretic gels from culture supernatants showed that the low fibrinolytic activity of culture supernatants of oral squamous cell carcinomas was due to the associated presence of plasminogen activator inhibitors. The fibrinolytic activity in the zymogram was due predominantly to uPA but some lysis was due also to tPA. PMID:1417524
Barlow, Y; Southam, J C
Dysfunction of CFTR in cystic fibrosis (CF) airway epithelium perturbs the normal regulation of ion transport, leading to a reduced volume of airway surface liquid (ASL), mucus dehydration, decreased mucus transport, and mucus plugging of the airways. CFTR is normally expressed in ciliated epithelial cells of the surface and submucosal gland ductal epithelium and submucosal gland acinar cells. Critical questions for the development of gene transfer strategies for CF airway disease are what airway regions require CFTR function and how many epithelial cells require CFTR expression to restore normal ASL volume regulation and mucus transport to CF airway epithelium? An in vitro model of human CF ciliated surface airway epithelium (CF HAE) was used to test whether a human parainfluenza virus (PIV) vector engineered to express CFTR (PIVCFTR) could deliver sufficient CFTR to CF HAE to restore mucus transport, thus correcting the CF phenotype. PIVCFTR delivered CFTR to >60% of airway surface epithelial cells and expressed CFTR protein in CF HAE approximately 100-fold over endogenous levels in non-CF HAE. This efficiency of CFTR delivery fully corrected the basic bioelectric defects of Cl? and Na+ epithelial ion transport and restored ASL volume regulation and mucus transport to levels approaching those of non-CF HAE. To determine the numbers of CF HAE surface epithelial cells required to express CFTR for restoration of mucus transport to normal levels, different amounts of PIVCFTR were used to express CFTR in 3%–65% of the surface epithelial cells of CF HAE and correlated to increasing ASL volumes and mucus transport rates. These data demonstrate for the first time, to our knowledge, that restoration of normal mucus transport rates in CF HAE was achieved after CFTR delivery to 25% of surface epithelial cells. In vivo experimentation in appropriate models will be required to determine what level of mucus transport will afford clinical benefit to CF patients, but we predict that a future goal for corrective gene transfer to the CF human airways in vivo would attempt to target at least 25% of surface epithelial cells to achieve mucus transport rates comparable to those in non-CF airways.
Gabriel, Sherif E.; Burkett, Susan; Yan, Yu; Skiadopoulos, Mario H.; Dang, Yan Li; Vogel, Leatrice N.; McKay, Tristan; Mengos, April; Boucher, Richard C.; Collins, Peter L.; Pickles, Raymond J.
Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye. PMID:24058402
Arnault, Emilie; Barrau, Coralie; Nanteau, Céline; Gondouin, Pauline; Bigot, Karine; Viénot, Françoise; Gutman, Emmanuel; Fontaine, Valérie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, José-Alain; Picaud, Serge
Among the identified risk factors of age-related macular degeneration, sunlight is known to induce cumulative damage to the retina. A photosensitive derivative of the visual pigment, N-retinylidene-N-retinylethanolamine (A2E), may be involved in this phototoxicity. The high energy visible light between 380 nm and 500 nm (blue light) is incriminated. Our aim was to define the most toxic wavelengths in the blue-green range on an in vitro model of the disease. Primary cultures of porcine retinal pigment epithelium cells were incubated for 6 hours with different A2E concentrations and exposed for 18 hours to 10 nm illumination bands centered from 380 to 520 nm in 10 nm increments. Light irradiances were normalized with respect to the natural sunlight reaching the retina. Six hours after light exposure, cell viability, necrosis and apoptosis were assessed using the Apotox-Glo Triplex™ assay. Retinal pigment epithelium cells incubated with A2E displayed fluorescent bodies within the cytoplasm. Their absorption and emission spectra were similar to those of A2E. Exposure to 10 nm illumination bands induced a loss in cell viability with a dose dependence upon A2E concentrations. Irrespective of A2E concentration, the loss of cell viability was maximal for wavelengths from 415 to 455 nm. Cell viability decrease was correlated to an increase in cell apoptosis indicated by caspase-3/7 activities in the same spectral range. No light-elicited necrosis was measured as compared to control cells maintained in darkness. Our results defined the precise spectrum of light retinal toxicity in physiological irradiance conditions on an in vitro model of age-related macular degeneration. Surprisingly, a narrow bandwidth in blue light generated the greatest phototoxic risk to retinal pigment epithelium cells. This phototoxic spectrum may be advantageously valued in designing selective photoprotection ophthalmic filters, without disrupting essential visual and non-visual functions of the eye.
Arnault, Emilie; Barrau, Coralie; Nanteau, Celine; Gondouin, Pauline; Bigot, Karine; Vienot, Francoise; Gutman, Emmanuel; Fontaine, Valerie; Villette, Thierry; Cohen-Tannoudji, Denis; Sahel, Jose-Alain; Picaud, Serge
BACKGROUND: Barrett's esophagus (BE) is the metaplastic replacement of squamous with columnar epithelium in the esophagus, as a result of reflux. It is the major risk factor for the development of esophageal adenocarcinoma (EAC). Methylation of CpG dinucleotides of normally unmethylated genes is associated with silencing of their expression, and is common in EAC. This study was designed to determine
Eric Smith; Neville J De Young; Sandra J Pavey; Nicholas K Hayward; Derek J Nancarrow; David C Whiteman; B Mark Smithers; Andrew R Ruszkiewicz; Andrew D Clouston; David C Gotley; Peter G Devitt; Glyn G Jamieson; Paul A Drew
Background: Chemo-radiotherapy for thoracic tumors can result in high-grade radiation esophagitis. Treatment planning to reduce esophageal irradiation requires organ motion to be accounted for. In this study, esophageal mobility was assessed using four-dimensional computed tomography (4DCT). Methods and Materials: Thoracic 4DCT scans were acquired on a 16-slice CT scanner in 29 patients. The outer esophageal wall was contoured in two extreme phases of respiration in 9 patients with nonesophageal malignancies. The displacement of the center of contour was measured at 2-cm intervals. In 20 additional patients with Stage I lung cancer, the esophagus was contoured in all 10 phases of each 4DCT at five defined anatomic levels. Both approaches were then applied to 4DCT scans of 4 patients who each had two repeat scans performed. A linear mixed effects model was constructed with fixed effects: measurement direction, measurement type, and measurement location along the cranio-caudal axis. Results: Measurement location and direction were significant descriptive parameters (Wald F-tests, p < 0.001), and the interaction term between the two was significant (p = 0.02). Medio-lateral mobility exceeded dorso-ventral mobility in the lower half of the esophagus but was of a similar magnitude in the upper half. Margins that would have incorporated all movement in medio-lateral and dorso-ventral directions were 5 mm proximally, 7 mm and 6 mm respectively in the mid-esophagus, and 9 mm and 8 mm respectively in the distal esophagus. Conclusions: The distal esophagus shows more mobility. Margins for mobility that can encompass all movement were derived for use in treatment planning, particularly for stereotactic radiotherapy.
Dieleman, Edith [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Senan, Suresh [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)]. E-mail: firstname.lastname@example.org; Vincent, Andrew [Department of Bioinformatics, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Lagerwaard, Frank J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Slotman, Ben J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Soernsen de Koste, John R. van [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)
Heparanase is an endo-beta-glucuronidase that specifically cleaves heparan sulfate (HS) chains. Heparanase is involved in the process of metastasis and angiogenesis through the degradation of HS chains of the extracellular matrix and cell surface. Recently, we demonstrated that heparanase was localized in the cell nucleus of normal esophageal epithelium and esophageal cancer, and that its expression was correlated with cell differentiation. However, the nuclear function of heparanase remains unknown. To elucidate the role of heparanase in esophageal epithelial differentiation, primary human esophageal cells were grown in monolayer as well as organotypic cultures, and cell differentiation was induced. Expression of heparanase, HS, involucrin, and p27 was determined by immunostaining and Western blotting. SF4, a novel pharmacological inhibitor, was used to specifically inhibit heparanase activity. Upon esophageal cell differentiation, heparanase was translocated from the cytoplasm to the nucleus. Such translocation of heparanase appeared to be associated with the degradation of HS chains in the nucleus and changes in the expression of keratinocyte differentiation markers such as p27 and involucrin, whose induction was inhibited by SF4. Furthermore, these in vitro observations agreed with the expression pattern of heparanase, HS, involucrin, cytokeratin 13, and p27 in normal esophageal epithelium. Nuclear translocation of heparanase and its catalytic cleavage of HS may play a critical role in the differentiation of esophageal epithelial cells. Our study provides a novel insight into the role of heparanase in an essential differentiation process. PMID:16759289
Kobayashi, Masahiko; Naomoto, Yoshio; Nobuhisa, Tetsuji; Okawa, Takaomi; Takaoka, Munenori; Shirakawa, Yasuhiro; Yamatsuji, Tomoki; Matsuoka, Junji; Mizushima, Takaaki; Matsuura, Hironori; Nakajima, Motowo; Nakagawa, Hiroshi; Rustgi, Anil; Tanaka, Noriaki
A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with 131I and documented a fall in LES pressure. We propose that abnormal smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism. PMID:7119407
Eastwood, G L; Braverman, L E; White, E M; Vander Salm, T J
The following on molecular aspects of esophageal development contains commentaries on esophageal striated myogenesis and transdifferentiation; conversion from columnar into stratified squamous epithelium in the mouse esophagus; the roles for BMP signaling in the developing esophagus and forestomach; and evidence of a direct conversion from columnar to stratified squamous cells in the developing esophagus. PMID:21950820
Rishniw, Mark; Rodriguez, Pavel; Que, Jianwen; Burke, Zoe D; Tosh, David; Chen, Hao; Chen, Xiaoxin
The following on molecular aspects of esophageal development contains commentaries on esophageal striated myogenesis and transdifferentiation; conversion from columnar into stratified squamous epithelium in the mouse esophagus; the roles for BMP signaling in the developing esophagus and forestomach; and evidence of a direct conversion from columnar to stratified squamous cells in the developing esophagus.
Rishniw, Mark; Rodriguez, Pavel; Que, Jianwen; Burke, Zoe D.; Tosh, David; Chen, Hao; Chen, Xiaoxin
Esophageal motility testing is the method of choice in evaluating esophageal motor disorders. Some physicians, however, question the clinical utility of esophageal motility testing, since the results are often normal in symptomatic patients. The clinical utility of esophageal motility testing is reviewed for patients with a complaint of noncardiac chest pain, dysphagia or symptoms of gastroesophageal reflux disease. Esophageal motility
Melvin L. Allen; Richard B. Lynn; Saeed Zamani
To determine whether EGFR tyrosine kinase domain muta- tions are early events in the pathogenesis of lung adenocarci- nomas, we tested for the presence of EGFR mutations in histologically normal bronchial and bronchiolar epithelia from lung adenocarcinomas bearing the common EGFR mutations. DNA was extracted from microdissected tissue obtained from 21 tumors with known EGFR mutations, 16 tumors without mutation,
Ximing Tang; Hisayuki Shigematsu; B. Nebiyou Bekele; Jack A. Roth; John D. Minna; Waun Ki Hong; Adi F. Gazdar; Ignacio I. Wistuba
Marked aneuploidy and loss of multiple chromosomes are hallmarks of cancer, but whether these events are only present in malignant cells is not known. In prior work, we showed that approximately half of spontaneous autosomal mutants isolated directly from normal kidney epithelium arose from loss of a marker chromosome 8 containing the wild type Aprt gene. Chromosome loss was detected by loss of heterozygosity (LOH) for all chromosome 8 polymorphic loci examined (Turker et al, Aging Cell, 6:73-86, 2007). To determine whether loss of chromosome 8 reflected a larger mitotic event, LOH was examined for polymorphic loci on 11 non-selected chromosomes in Aprt mutants that lost the selected chromosome 8 homologue. LOH events were detected for one or more non-selected chromosomes in 38% of these mutants. The additional LOH events also reflected apparent chromosome loss based on the molecular analysis. Metaphase spreads from mutants that lost chromosome 8 were markedly aneuploid and chromosome painting revealed reduced levels for any chromosome shown to be lost with the LOH analysis. In contrast, LOH on non-selected chromosomes was infrequent in Aprt mutants exhibiting intragenic events or mitotic recombination for chromosome 8, and marked aneuploidy was absent. These observations suggest that the mechanism leading to chromosome loss in somatic mammalian cells is often not a simple non-disjunction event and instead could result from a single catastrophic event. They also suggest that cells with characteristics of malignancy are present in normal appearing tissue.
Dan, Cristian; Grygoryev, Dymtro; Sandfort, Kelly; Connolly, Marissa; Cross, Brittany; Lasarev, Michael; Kronenberg, Amy; Turker, Mitchell S.
Marked aneuploidy and loss of multiple chromosomes are hallmarks of cancer, but whether these events are only present in malignant cells is not known. In prior work, we showed that approximately half of spontaneous autosomal mutants isolated directly from normal kidney epithelium arose from loss of a marker chromosome 8 containing the wild type Aprt gene. Chromosome loss was detected by loss of heterozygosity (LOH) for all chromosome 8 polymorphic loci examined. To determine whether loss of chromosome 8 reflected a larger mitotic event, LOH was examined for polymorphic loci on 11 nonselected chromosomes in Aprt mutants that lost the selected chromosome 8 homologue. LOH events were detected for one or more nonselected chromosomes in 38% of these mutants. The additional LOH events also reflected apparent chromosome loss based on the molecular analysis. Metaphase spreads from mutants that lost chromosome 8 were markedly aneuploid, and chromosome painting revealed reduced levels for any chromosome shown to be lost with the LOH analysis. In contrast, LOH on nonselected chromosomes was infrequent in Aprt mutants exhibiting intragenic events or mitotic recombination for chromosome 8, and marked aneuploidy was absent. These observations suggest that the mechanism leading to chromosome loss in somatic mammalian cells is often not a simple nondisjunction event and instead could result from a single catastrophic event. They also suggest that cells with characteristics of malignancy are present in normal appearing tissue. PMID:21254298
Dan, Cristian; Grygoryev, Dmytro; Sandfort, Kelly; Connolly, Marissa; Cross, Brittany; Lasarev, Michael; Kronenberg, Amy; Turker, Mitchell S
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. PMID:23460081
Roscioli, Eugene; Hamon, Rhys; Lester, Susan; Murgia, Chiara; Grant, Janet; Zalewski, Peter
Mucosal epithelium of pyloric caeca was studied in normal and in GnRH-treated Atlantic bluefin tuna Thunnus thynnus L., using morphological analysis, conventional and lectin glycohistochemistry. The lining epithelium consisted of columnar (absorptive) cells, goblet cells and intraepithelial leucocytes. The epithelium from normal animals was significantly taller than GnRH-treated samples. Conventional histochemistry displayed the same staining pattern in normal and hormone-treated specimens which showed a mixture of neutral and sulphated acidic glycoconjugates in the luminal surface and goblet cells, and neutral glycans in apical granules of enterocytes. Lectin histochemistry revealed a different glycoconjugate pattern in normal and GnRH-treated tunas. In normal specimens the luminal surface expressed sialoglycoconjugates which bound MAL II, SNA, KOH-sialidase-PNA, KOH-sialidase-SBA as well as asialoglycans stained with HPA, SBA, GSA I-B4 , LTA. N-linked glycans were highlighted by Con A and KOH-sialidase-WGA. In GnRH-treated tunas the luminal surface did not react with SNA, SBA and LTA. The columnar cells of normal tunas bound KOH-sialisase-PNA in the apical region, KOH-sialidase-PNA, KOH-sialidase-DBA, HPA, SBA, KOH-sialidase-SBA and KOH-sialidase-WGA in apical granules, GSA I-B? and LTA in the supranuclear region. GnRH-treated specimens showed some columnar cells that stained with KOH-sialidase-WGA in the apical granules and with GSA I-B4 in the supranuclear region. The goblet cells of normal animals produced mucins positive to PNA, HPA, KOH-sialidase-DBA, SBA, GSA II. The latter three binding sites lacked in GnRH-treated tunas. The results suggest that the mucosal epithelium of Thunnus thynnus L. pyloric caeca expresses a complex glycan pattern that is affected by GnRH-treatment. PMID:23939675
Zizza, Sara; Desantis, Salvatore
Mucosal epithelium of pyloric caeca was studied in normal and in GnRH-treated Atlantic bluefin tuna Thunnus thynnus L., using morphological analysis, conventional and lectin glycohistochemistry. The lining epithelium consisted of columnar (absorptive) cells, goblet cells and intraepithelial leucocytes. The epithelium from normal animals was significantly taller than GnRH-treated samples. Conventional histochemistry displayed the same staining pattern in normal and hormone-treated specimens which showed a mixture of neutral and sulphated acidic glycoconjugates in the luminal surface and goblet cells, and neutral glycans in apical granules of enterocytes. Lectin histochemistry revealed a different glycoconjugate pattern in normal and GnRH-treated tunas. In normal specimens the luminal surface expressed sialoglycoconjugates which bound MAL II, SNA, KOH-sialidase-PNA, KOH-sialidase-SBA as well as asialoglycans stained with HPA, SBA, GSA I-B(4), LTA. N-linked glycans were highlighted by Con A and KOH-sialidase-WGA. In GnRH-treated tunas the luminal surface did not react with SNA, SBA and LTA. The columnar cells of normal tunas bound KOH-sialisase-PNA in the apical region, KOH-sialidase-PNA, KOH-sialidase-DBA, HPA, SBA, KOH-sialidase-SBA and KOH-sialidase-WGA in apical granules, GSA I-B(4) and LTA in the supranuclear region. GnRH-treated specimens showed some columnar cells that stained with KOH-sialidase-WGA in the apical granules and with GSA I-B(4) in the supranuclear region. The goblet cells of normal animals produced mucins positive to PNA, HPA, KOH-sialidase-DBA, SBA, GSA II. The latter three binding sites lacked in GnRH-treated tunas. The results suggest that the mucosal epithelium of Thunnus thynnus L. pyloric caeca expresses a complex glycan pattern that is affected by GnRH-treatment. Microsc. Res. Tech., 2010. © 2010 Wiley-Liss, Inc. PMID:21165985
Zizza, Sara; Desantis, Salvatore
Diffuse esophageal spasm is an uncommon motility disorder that is found in less than 5% of patients undergoing esophageal motility testing for dysphagia. It is defined manometrically by the presence of 20% or more simultaneous contractions in the distal esophageal body with normal peristalsis. This motility abnormality has been traditionally identified as occurring primarily in the smooth muscle portion of
Monicca Sperandio; Radu Tutuian; R. Matthew Gideon; Philip O. Katz; Donald O. Castell
Careful normalization is essential for the accurate quantitation of mRNA levels in biopsy-sized tissue samples. Commonly, normalization of the target gene with an endogenous standard, mainly housekeeping genes (HKGs), is applied. However, differences in the expression levels of endogenous reference genes have been reported between different tissues and pathological states. Therefore, we were challenged to identify a set of endogenous
Claudia Rubie; Katja Kempf; Joachim Hans; Tiefen Su; Bettina Tilton; Thomas Georg; Brigitte Brittner; Bianca Ludwig; Martin Schilling
Purpose Previously, we found that gene expression in histologically normal breast epithelium (NlEpi) from women at high breast cancer risk can resemble gene expression in NlEpi from cancer-containing breasts. Therefore, we hypothesized that gene expression characteristic of a cancer subtype might be seen in NlEpi of breasts containing that subtype. Experimental Design We examined gene expression in 46 cases of microdissected NlEpi from untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 estrogen receptor (ER)+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9 ER+, 7 ER-), we validated selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results We identified 198 genes that are differentially expressed between NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers (e.g., ESR1, GATA3, and CX3CL1, FABP7). QPCR validated the microarray results in both the 30 original cases and the 16 independent cases. Gene expression in NlEpiER+ and NlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 25-53% of the genes or probes examined in 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. NlEpi gene expression may help elucidate subtype-specific risk signatures, identify early genomic events in cancer development and locate targets for prevention and therapy.
Graham, Kelly; Ge, Xijin; de las Morenas, Antonio; Tripathi, Anusri; Rosenberg, Carol L.
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.
Overholt, Bergein F.; Panjehpour, Masoud
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.
Overholt, Bergein F.; Panjehpour, Masoud
Summary The c-erbB-2 (HER-2\\/neu) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor (EGFR). We examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. The ovarian tumours were classified as benign (16), borderline malignant (2),
Da-peng Wang; Ikuo Konishi; Masafumi Koshiyama; Yoshihiko Nanbu; Toshiko Iwai; Hirofumi Nonogaki; Takahide Mori; Shingo Fujii
Both intracellular calcium ions and neural input are important in esophageal smooth muscle contraction. The aim of this study was to compare the effects of well-tolerated doses of the calcium-channel blocker, nifedipine (20 mg sublingually\\/buccally) with the anticholinergic, propantheline bromide (15 mg orally) and the combination of these two agents on esophageal motor function. Seven healthy volunteers underwent manometric evaluation
Michio Hongo; Morris Traube; Richard W. McCallum
Background: Damage to the airway epithelium is one prominent feature of the damage seen in chronic asthma. Cortico-steroids induce apoptosis in inflammatory cells, which in part explains their ability to suppress airway inflammation. However, corticosteroid therapy does not necessarily reverse the epithelial damage seen in asthmatic airways. Objective: We hypothesized that corticosteroids might induce airway epithelial cell apoptosis as one
Delbert R. Dorscheid; Erika Low; Amber Conforti; Seth Shifrin; Anne I. Sperling; Steven R. White
The fasting lower esophageal sphincter pressure of 18 normal volunteers was compared to 22 patients with symptoms and objective evidence of gastroesophageal reflux. Lower esophageal sphincter pressure was measured by rapid pull-through using an 8-lumen radially perfused catheter that sampled pressure every45 degrees around the circumference of the sphincter. The 22 reflux patients were subdivided for analysis into two groups, those with an acute inflammatory infiltrate on biopsy and those without inflammation. Those patients without inflammatory esophagitis had normal sphincter pressures. Those with a definite inflammatory infiltrate had pressures significantly less than normal. The least reliable separation between normals and those with inflammatory esophagitis occurred in the anterior orientations. We conclude that while basal lower esophageal sphincter pressure measurement may identify patients with reflux and inflammatory esophagitis, it is of no help in identifying those patients with reflux unassociated with inflammation. Decreased basal fasting LESP does not appear to be the most important primary determinant of gastroesophageal reflux. PMID:7379675
Welch, R W; Luckmann, K; Ricks, P; Drake, S T; Bannayan, G; Owensby, L
Esophageal manometry was performed in 20 patients with esophagopharyngeal regurgitation, in 20 patients with severe chronic heartburn but without regurgitation, and in 20 normal subjects. The purpose of the procedure was to identify possible differences between these groups in upper esophageal sphincter and lower esophageal sphincter resting pressures, and in amplitude of peristaltic contraction in the distal esophagus. The mean peak upper esophageal sphincter pressures in normal subjects and in patients with chronic heartburn were significantly greater than in the patients with esophagopharyngeal regurgitation (101 and 108 vs. 54 mmHg, respectively). In the normal subjects, the mean lower esophageal sphincter resting pressure (19 mmHg) was significantly greater than for the heartburn group (14 mmHg) and for the patients with esophagopharyngeal regurgitation (10 mmHg). The amplitude of peristalsis was significantly lower in the group with regurgitation than in both normal subjects and the group with chronic heartburn. Nine normal subjects responded to intraesophageal infusion of 0.9% NaCl and 0.1 N HCl with a significant increase in upper esophageal sphincter resting pressure, but the group with esophagopharyngeal regurgitation showed no significant change. Patients with esophagopharyngeal regurgitation have lower esophageal sphincter hypotension, diminished peristaltic amplitude, upper esophageal sphincter hypotension, and diminished upper esophageal sphincter response to intraesophageal fluid. We conclude there is in these patients a breakdown of several normal esophageal mechanisms which ordinarily serve as barriers to esophagopharyngeal regurgitation. PMID:7053042
Gerhardt, D C; Castell, D O; Winship, D H; Shuck, T J
Primary esophageal tuberculosis is virtually non-existent and there are few cases described of secondary esophageal tuberculosis. Esophageal tuberculosis should be suspected in patients with dysphagia, positive test results for tuberculin, active pulmonary disease or mediastinal adenopathies. Endoscopic or x-ray images could be indistinguishable from esophageal carcinomas, hence a diagnosis can prevent wrong treatments. Confirming the diagnosis requires isolation of tuberculosis bacillus. Treatment for a patient with esophageal tuberculosis is standard therapy. Key words: Tuberculosis, esophagus. PMID:16865167
Baños, Ramón; Serrano, Andrés; Alberca, Fernando; Alajarín, María; Albaladejo, Aquilino; Vargas, Angel; Molina, Joaquín
As an incidental finding in paraffin sections of brain tissue used as positive controls for synaptophysin immunostain, the cytoplasm of choroid plexus epithelium present was found to stain strongly positively for this substance. This was subsequently found to be the case in normal choroid plexuses in autopsy material from infancy to old age, as well as in epithelial cells of papillomas and carcinomas of the choroid plexus. The latter findings may prove useful in differentiating choroid plexus carcinomas from metastatic papillary carcinomas of extracerebral origin with the exception of neuroendocrine carcinomas of various sites that are usually positive for synaptophysin. PMID:10218635
Kepes, J J; Collins, J
Small numbers of intraepithelial esophageal eosinophils (IEE) may be seen in 50% of patients with gastroesophageal reflux disease and occasionally in normal volunteers. High concentrations of IEE are rarely seen in either setting. During a two-year period we idetified 12 adult patients with very dense eosinophil infiltrates in esophageal biopsies (defined as >20 IEE\\/high-power field). Dysphagia was the presenting complaint
Stephen E. A. Attwood; Thomas C. Smyrk; Tom R. Demeester; James B. Jones
Expression of keratins 1, 6, 15, 16, and 20 was examined in normal cervical epithelia, squamous metaplasia, various grades of cervical intraepithelial neoplasia, and both squamous cell carcinomas and adenocarcinomas of the cervix with monospecific antibodies. Ectocervical epithelium contains all of these keratins except keratin 20. They show a heterogeneous distribution, with a basally restricted detection of keratin 15. Endocervical columnar cells were found to contain significant amounts of keratin 16, whereas the subcolumnar reserve cells expressed considerable amounts of keratin 15 and 16, and frequently keratin 6. These reserve cell keratins were also found in immature and mature squamous metaplastic epithelium. In the cervical intraepithelial neoplastic lesions they were generally found with increasing intensity as the severity of the lesion progressed. In the keratinizing variety of squamous cell carcinoma of the cervix, these three keratins seem to constitute an important part of the intermediate filament cytoskeleton, whereas in nonkeratinizing squamous cell carcinoma, they occur to a much lesser extent. Surprisingly, these keratins were also occasionally found in adenocarcinomas. From these data we conclude that the keratin phenotype of reserve cells and endocervical columnar cells is more complex than previously suggested. In particular, the keratins occurring in reserve cells are also present in most of the premalignant and in a considerable number of the malignant lesions of the cervix. The differentiation features of the various carcinoma types are, however, reflected in their specific keratin filament composition. Images Figure 2 Figure 3 Figure 4 Figure 5
Smedts, F.; Ramaekers, F.; Leube, R. E.; Keijser, K.; Link, M.; Vooijs, P.
The author reviewed 910 cases of consecutive esophageal biopsies in the last 15 year in the pathology laboratory of our hospital. There were 693 normal mucosa and benign lesions (76.2%) and 217 malignant lesions (23.8%). No significant changes were recognized in the esophagus in 50 biopsies (5.5%). In benign lesions, the number and frequency (percentages) were as follows: 263 chronic esophagitis (28.9%), 98 heterotopic gastric mucosa (10.8%), 3 heterotopic colonic mucosa (0.3%), 71 glycogenic acanthosis (7.8%), 68 candidiasis (7.5%), 35 benign ulcer (3.8%), 41 squamous papilloma (4.5%), 4 granular cell tumor (0.4%), 1 tubular adenoma (0.1%), 2 cytomegalovirus esophagitis (0.2%), 3 leiomyoma (0.3%), 17 basal cell hyperplasia (1.9%), and 37 Barrett’s epithelium (4%). In malignant lesions, the number and frequency (percentages) were as follows: 53 mild dysplasia (5.8%), 29 moderate dysplasia (3.2%), 31 severe dysplasia (3.4%), 13 carcinoma in situ (1.4%), 68 squamous cell carcinoma (7.5%), 7 primary adenocarcinoma (0.8%), 1 primary signet ring cell carcinoma (0.1%), 4 primary small cell carcinoma (0.4%), 2 primary amelanotic malignant melanoma (0.2%), 1 primary undifferentiated sarcoma (0.1%), 7 gastric cancer invasion (0.8%), and 1 primary adenoid cystic carcinoma (0.1%). In this article, the clinicopathologic features of these esophageal lesions were described.
AIM: To examine the value of immunohistochemistry in defining a keratin profile to aid cervical histopathological diagnosis. METHODS: Immunohistochemical localisation of keratins 17, 10, and 19 was studied in 268 cervical biopsies from 216 women including normal epithelia (with and without human papilloma virus), low and high grade cervical intraepithelial neoplasia, and invasive carcinoma. The percentage of positive immunostaining was scored using a Kontron MOP videoplan image analyser. RESULTS: All major categories of cervical epithelia expressed these keratins to varying degrees. The median percentage of immunostaining for keratin 10 was 40% in normal tissue compared with just 1% in invasive carcinoma (p < 0.0001). The medians for keratin 17 were 0% in the normal group and 80% in carcinomas (p < 0.0001). By contrast, there was no significant difference in staining for keratin 19. Using a combination of the keratin 10 and 17 percentages, it was possible to separate the carcinomas from the benign conditions with a sensitivity of 100% and a specificity of 93%. Further analyses within the groups revealed more extensive staining for keratins 10 and 19 in reserve cell hyperplasia, immature squamous metaplasia, and congenital transformation zone. CONCLUSIONS: The morphological variety within the cervix is reflected, in part, by distinct keratin patterns. There are striking differences in the patterns of keratins 10 and 17 between infiltrating squamous carcinoma and normal cervical epithelia.
Maddox, P; Sasieni, P; Szarewski, A; Anderson, M; Hanby, A
Osteogenesis imperfecta (OI) is a clinically heterogeneous heritable connective tissue disorder, characterized by low bone mass and reduced strength, which result in susceptibility to fracture and bone deformities. In most cases it is caused by dominant mutations in type I collagen genes, COL1A1 and COL1A2. Recessive forms, which collectively account for approximately 5% of cases of osteogenesis imperfecta detected in North America and Europe, are caused instead by mutations in various genes coding for proteins involved in collagen posttranslational modifications, folding, and secretion. A novel disease locus, SERPINF1, coding for pigment epithelium-derived factor (PEDF), has been found recently. In SERPINF1 mutants described so far, synthesis, posttranslational modification, and secretion of type I collagen were reported to be normal. Here we describe three siblings born to consanguineous parents, who show an initially mild and then progressively worsening form of OI with severe deformities of the long bones. They are homozygous for a frameshift mutation in exon 4 of the SERPINF1 gene, which leads to lack of the transcription/translation product, likely a key factor in bone deposition and remodeling. Synthesis and secretion of type I collagen are normal. Clinical, radiographic, histological, and histomorphometric data from the proband are reminiscent of the distinctive features of type VI OI. PMID:22113968
Venturi, Giacomo; Gandini, Alberto; Monti, Elena; Dalle Carbonare, Luca; Corradi, Massimiliano; Vincenzi, Monica; Valenti, Maria Teresa; Valli, Maurizia; Pelilli, Enrico; Boner, Attilio; Mottes, Monica; Antoniazzi, Franco
Background Esophageal intestinal metaplasia, also known as Barrett’s esophagus, is the replacement of the normal epithelium with one that resembles the intestine morphologically. Generally, this includes intestinal mucin-secreting goblet cells. Barrett’s esophagus is an important risk factor for adenocarcinoma development. In vitro models for Barrett’s esophagus have not, to date, focused on the induction of goblet cells in Barrett’s epithelium. Aims To explore the contribution of Math1/Atoh1 in the induction of Barrett’s esophagus and intestinal mucin-secreting goblet cells from normal human esophageal epithelium. Methods We explored the level and pattern of Math1/Atoh1 mRNA and protein expression in human Barrett’s esophagus. Then, using retroviral-mediated gene expression, we induced Math1 mRNA and protein expression in a human esophageal keratinocyte cell line. We evaluated the effects of this ectopic Math1 expression upon cell proliferation and gene expression patterns in cells cultured under 2-dimensional and 3-dimensional tissue engineering conditions. Results Math1/Atoh1 mRNA and protein are detected in human Barrett’s esophagus specimens, but the mRNA levels vary considerable. In the keratinocyte expression studies, we observed that Math1/Atoh1 ectopic expression significantly reduced cell proliferation and altered cell morphology. Moreover, Math1/Atoh1 expression is associated with a more intestinalized gene expression pattern that is distinct from prior published studies using other intestinal transcription factors. Most significantly we observe the induction of the Barrett’s esophagus markers Mucin-2 and Keratin-20 with Math1/Atoh1 expression. Conclusions We conclude that ectopic Math1/Atoh1 expression makes unique contributions to the intestinalization of esophageal epithelium in Barrett’s esophagus.
Kong, Jianping; Crissey, Mary Ann S.; Sepulveda, Antonia R.; Lynch, John P.
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. PMID:23299406
King, Shelby M; Quartuccio, Suzanne M; Vanderhyden, Barbara C; Burdette, Joanna E
Twelve patients with known esophageal varices and willingness to cooperate were included in the study. Medications administered were placebo, 2 mg of glucagon, and 30 mg of propantheline bromide. All medications were given double-blind and crossover. On the basis of this study the authors believe that for optimal visualization of esophageal varices the following is the procedure of choice: (I)
EDWARD M. COCKERILL; ROSCOE E. MILLER; STANLEY M. CHERNISH; GORDON C. McLAUGHLIN; BRUCE E. RODDA
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
Bednarczyk, D; Smigiel, R; Patkowski, D; Laczmanska, I; Lebioda, A; Laczmanski, L; Sasiadek, M M
The cambial and daughter cells of normal epithelium function in the morphofunctional zone consisting of two subunits with 12 cambial cells in each. Daughter cells are differentiated in an electrical field created by 12 pairs of maternal and daughter cells, products of division of cambial cells located in the same subunit. The differentiation requires relaxation of the cortex of daughter cells via expression of SH3 domain of Src kinase by dermal daughter cells, which leads to a decrease in activity of RhoA in epidermal cells, their stretching, and activation of SH2 domain of Src responsible for differentiation. Reduction of the number of cambial cells to 6 and, consequently, weakening of electrical field produced by them to a threshold value corresponding to very weak stretching of daughter epithelial cells results in a decrease in SH2 domain expression in these cells and its kinase contribution in Src. This leads to an increase in RhoA relative to Src, enhances cell contraction, impairs formation of stress fibrils and focal contacts, reduces cell flattening, and increases cell mobility. The decrease in the number of microtubules, intermediate filaments, and stress-fibrils changes the major cell axis direction, which, in turn, sharply reduces nucleus stretching and leads to impaired chromosome looping out near the centromeres and telomeres; the cells acquires signs of an epitheliocyte and a fibroblast, protein transcription is impaired, and daughter cells are transformed into malignant cell. PMID:21234456
Yavisheva, T M; Shcherbakov, S D
The aim of the study was to evaluate the expression of tumor suppressor genes p53, fragile histidine triad gene (FHIT), and an oncogene insulin-like growth factor 2 (IGF2) as prognostic markers in the etiology of esophageal cancer. Immunohistochemistry (IHC) was performed in 39 archival tissue samples of different esophageal pathologies for the three genes. Abnormal p53 expression was maximum in all the cases of squamous cell carcinoma, while IGF2 expression was enhanced in squamous cell carcinoma (81%), adenocarcinoma (100%), and dysplasia of squamous epithelium (75%) samples when compared with normals (50%). To our surprise, 75% of normal tissues did not show FHIT expression, which was also not seen in 40% of dysplasias of squamous epithelium, 33.3% of adenocarcinoma, and 41% of squamous cell carcinoma. To the best of our knowledge, this is the first study evaluating IGF2 by IHC, as well as, correlating it with the expression of the two tumor suppressor genes, p53 and FHIT, in esophageal tissue. p53 expression was threefold higher than normal in dysplasias of squamous epithelium and adenocarcinoma, while it was eightfold higher in squamous cell carcinoma. IGF2 expression was low in normal and dysplasia tissue but was increased 1.97-fold in both types of malignancy. FHIT and p53 expression were well correlated in squamous cell carcinoma, supporting the observation that FHIT regulates and stabilizes p53. Altered/lowered FHIT levels may be a result of exposure to various exogenous agents; however, this could not be assessed in the present study as it was carried out on archival samples. A larger prospective study is warranted to establish the role of exogenous factors in FHIT expression. PMID:21668571
Chava, S; Mohan, V; Shetty, P J; Manolla, M L; Vaidya, S; Khan, I A; Waseem, G L; Boddala, P; Ahuja, Y R; Hasan, Q
The objective of this exploratory study was to evaluate the feasibility of using Fourier-Transform Infrared (FTIR) spectromicroscopy to characterize formalin-fixed, paraffin-embedded human esophageal tissues. Matched histologically normal esophageal squamous epithelium (NS), premalignant Barrett esophagus (BE), and primary esophageal adenocarcinoma (EADC) tissues, each defined according to strict clinicopathologic criteria, were obtained from patients who underwent esophageal resection. Using confocal IR microscopy, measurements in the mid-IR spectral region were carried out in transflection configuration, scanning regions of interest in 15 microm steps. A multidimensional dataset reporting the spectroscopic properties at each sampled point were analyzed by performing a hierarchical cluster analysis on the second derivative of spectral traces. Normal esophageal epithelia were characterized by a few well defined regions, mostly of large size (tens of contiguous pixels), which correlated with tissue histology, specifically the basal cell layer. BE tissues had characteristic regions localized to gland crypts, ranging in size from one pixel to a few tens of pixels, which displayed IR spectra with defined absorption features characteristic of glycoproteins. The incorporation of synchrotron light to improve the resolution of individual cells in BE tissues has demonstrated that these glycoproteins are associated with goblet cells, the characteristic cell type defining BE. Whereas the highly fragmented regions identified in EADC likely reflect tumor heterogeneity, FTIR mapping would appear to be a potentially useful technique to identify premalignant BE tissues. The technical feasibility of using FTIR to characterize formalin-fixed, paraffin-embedded human esophageal tissues demonstrates the potential of this technique to study archival human BE tissue specimens via automated screening techniques. PMID:19475154
Quaroni, Luca; Casson, Alan G
This book contains the proceedings on esophageal cancer. Topics covered include: Scope of the problem, Diagnostic considerations: Methods of early diagnosis, Staging criteria, Elective surgical management, and Postoperative complications.
Delarue, N.C. (Univ. of Toronto, Toronto (CA)); Wilkins, E.W. Jr. (Harvard Medical School, MA (US)); Wong, J. (Dept. of Surgery, Univ. of Hong Kong (HK))
Eosinophilic esophagitis is a chronic inflammatory disorder characterized by dense eosinophilic infiltration of the esophageal\\u000a mucosa. The pathogenesis is incompletely understood and food allergies and aeroallergens have been implicated. The most common\\u000a clinical presentation in adults is dysphagia to solids. Its associated endoscopic findings are distinct and include concentric\\u000a rings and longitudinal furrows, although endoscopy may be unremarkable in a
Fouad J. Moawad; Ganesh R. Veerappan; Roy K. Wong
Despite progress in the management of esophageal perforations by early diagnosis, antibiotics, monitoring, and respiratory and nutritional support, it still remains as a disasterous condition. The most common cause of esophageal perforation is iatrogenic disruption. The result in the management of esophageal perforation is influenced by several factors: localization and size of the rupture, length of delay in diagnosis, age, extent of mediastinal and pleural contamination, the presence of underlying esophageal diseases, and inflammation or tumor at the perforation localization. In this study, 7 cases of esophageal perforations in the last six years have been analysed retrospectively. In study group, there were 5 males and 2 females, and the mean age was 36 (12-75). The most common cause of perforation was gunshot injury (3 cases), and stab wound (1 case), foreign body (1 case), iatrogenic distruption (2 cases). Three patients died and four patients were discharged from hospital with recovery. Esophageal perforation is a life-threatening condition. Early diagnosis and repair reduces the morbidity and mortality. PMID:11705168
Ertekin, C; Yanar, H T; Gülo?lu, R; Tavilo?lu, K; Dilege, S
AIM: To study the endocytoscopic visualization of squamous cell islands within Barrett’s epithelium. METHODS: Endocytoscopy (ECS) has been studied in the surveillance of Barrett’s esophagus, with controversial results. In initial studies, however, a soft catheter type endocytoscope was used, while only methylene blue dye was used for the staining of Barrett’s mucosa. Integrated type endocytoscopes (GIF-Q260 EC, Olympus Corp, Tokyo, Japan) have been recently developed, with the incorporation of a high-power magnifying endocytoscope into a standard endoscope together with narrow-band imaging (NBI). Moreover, double staining with a mixture of 0.05% crystal violet and 0.1% of methylene blue (CM) during ECS enables higher quality images comparable to conventional hematoxylin eosin histopathological images. RESULTS: In vivo endocytoscopic visualization of papillary squamous cell islands within glandular Barrett’s epithelium in a patient with long-segment Barrett’s esophagus is reported. Conventional white light endoscopy showed typical long-segment Barrett’s esophagus, with small squamous cell islands within normal Barrett’s mucosa, which were better visualized by NBI endoscopy. ECS after double CM staining showed regular Barrett’s esophagus, while higher magnification (× 480) revealed the orifices of glandular structures better. Furthermore, typical squamous cell papillary protrusion, classified as endocytoscopic atypia classification (ECA) 2 according to ECA, was identified within regular glandular Barrett’s mucosa. Histological examination of biopsies taken from the same area showed squamous epithelium within glandular Barrett’s mucosa, corresponding well to endocytoscopic findings. CONCLUSION: To our knowledge, this is the first report of in vivo visualization of esophageal papillary squamous cell islands surrounded by glandular Barrett’s epithelium.
Eleftheriadis, Nicholas; Inoue, Haruhiro; Ikeda, Haruo; Onimaru, Manabu; Yoshida, Akira; Hosoya, Toshihisa; Maselli, Roberta; Kudo, Shin-ei
Esophageal cancers are highly malignant tumours with often a poor prognostic, except for minimal lesions treated with surgery. Radiation therapy, or combined radiation and chemotherapy is the most used therapeutic modality, alone or before oesophagectomy. The delineation of target volumes is now more accurate owing the possibility to use routinely the new imaging techniques (mainly PET). The aim of this work is to precise the radio-anatomical particularities, the pattern of spread of esophageal cancer and the principles of 3D conformal radiotherapy illustrated with a clinical case. PMID:21129673
Dupuis, O; Ganem, G; Béra, G; Pointreau, Y; Pradier, O; Martin, P; Mirabel, X; Denis, F
Eosinophilic esophagitis is a chronic inflammatory disorder characterized by dense eosinophilic infiltration of the esophageal mucosa. The pathogenesis is incompletely understood and food allergies and aeroallergens have been implicated. The most common clinical presentation in adults is dysphagia to solids. Its associated endoscopic findings are distinct and include concentric rings and longitudinal furrows, although endoscopy may be unremarkable in a minority of patients. A number of management strategies exist; however, data are limited in adults, and only a few are based on randomized controlled trials. Management options include dietary modifications, pharmacological therapy, and endoscopic dilation. PMID:19554448
Moawad, Fouad J; Veerappan, Ganesh R; Wong, Roy K
Esophageal adenocarcinoma (EAC) has become a major concern in Western countries due to rapid rises in incidence coupled with very poor survival rates. One of the key risk factors for the development of this cancer is the presence of Barrett's esophagus (BE), which is believed to form in response to repeated gastro-esophageal reflux. In this study we performed comparative, genome-wide expression profiling (using Illumina whole-genome Beadarrays) on total RNA extracted from esophageal biopsy tissues from individuals with EAC, BE (in the absence of EAC) and those with normal squamous epithelium. We combined these data with publically accessible raw data from three similar studies to investigate key gene and ontology differences between these three tissue states. The results support the deduction that BE is a tissue with enhanced glycoprotein synthesis machinery (DPP4, ATP2A3, AGR2) designed to provide strong mucosal defenses aimed at resisting gastro-esophageal reflux. EAC exhibits the enhanced extracellular matrix remodeling (collagens, IGFBP7, PLAU) effects expected in an aggressive form of cancer, as well as evidence of reduced expression of genes associated with mucosal (MUC6, CA2, TFF1) and xenobiotic (AKR1C2, AKR1B10) defenses. When our results are compared to previous whole-genome expression profiling studies keratin, mucin, annexin and trefoil factor gene groups are the most frequently represented differentially expressed gene families. Eleven genes identified here are also represented in at least 3 other profiling studies. We used these genes to discriminate between squamous epithelium, BE and EAC within the two largest cohorts using a support vector machine leave one out cross validation (LOOCV) analysis. While this method was satisfactory for discriminating squamous epithelium and BE, it demonstrates the need for more detailed investigations into profiling changes between BE and EAC.
Nancarrow, Derek J.; Clouston, Andrew D.; Smithers, B. Mark; Gotley, David C.; Drew, Paul A.; Watson, David I.; Tyagi, Sonika; Hayward, Nicholas K.; Whiteman, David C.
A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly sug- gest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed.
Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo
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 mayprovide insights into the origins of EAC and maysuggest new therapies. To elucidate the molecular pathways of bile acid-induced tumorigenesis, the newly
Chia-Jui Yen; Julie G. Izzo; Dung-Fang Lee; Sushovan Guha; Jung-Mao Hsu; Hui-Lung Sun; Chao-Kai Chou; Navtej S. Buttar; Kenneth K. Wang; Peng Huang; Jaffer Ajani
Objective Eosinophilic esophagitis (EoE) is characterized by infiltration of eosinophils into esophageal epithelium. Blood levels of an eosinophil granule protein, eosinophil-derived neurotoxin (EDN), have been proposed as a biomarker for EoE. However, information regarding localization of EDN in the diseased tissues has not been available. The goal of this study was to evaluate the magnitude and distribution of EDN deposition in tissue specimens from the esophagus of EoE patients. Methods We studied specimens from 10 adult EoE patients and 8 histologically-normal controls (three under age 17). Sections from mid-esophageal biopsy specimens were stained for EDN by immunofluorescence, using a polyclonal rabbit antibody to EDN. Cellular staining (i.e. infiltration of intact eosinophils) and extracellular staining (i.e. deposition of released EDN) were scored in a blinded manner on an established 7-point scale. Results Esophageal biopsy specimens from histologically-normal controls showed no or few intact eosinophils and no or minimal extracellular EDN deposition. In contrast, EDN staining was clearly observed in specimens from all EoE patients. In some EoE patients, marked extracellular EDN deposition was observed despite relatively small numbers of intact eosinophils. Overall, there was no correlation between the eosinophil infiltration and the extracellular EDN staining scores. Conclusions Marked tissue deposition of extracellular EDN is present in the esophagus of EoE patients. Tissue eosinophil counts may underestimate how extensively eosinophils are involved, particularly in individuals with marked eosinophil degranulation. Evaluation of EDN staining in esophageal biopsy specimens may be useful to diagnose and manage patients with EoE.
Kephart, Gail M.; Alexander, Jeffrey A.; Arora, Amindra S.; Romero, Yvonne; Smyrk, Thomas C.; Talley, Nicholas J.; Kita, Hirohito
The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation.
Esophageal cancer is a prototypic squamous cell cancer that carries a poor prognosis, primarily due to presentation at advanced stages. We used human esophageal epithelial cells as a platform to recapitulate esophageal squamous cell cancer, thereby providing insights into the molecular pathogenesis of squamous cell cancers in general. This was achieved through the retroviral-mediated transduction into normal, primary human esophageal epithelial cells of epidermal growth factor receptor (EGFR), the catalytic subunit of human telomerase (hTERT), and p53(R175H), genes that are frequently altered in human esophageal squamous cell cancer. These cells demonstrated increased migration and invasion when compared with control cells. When these genetically altered cells were placed within the in vivo-like context of an organotypic three-dimensional (3D) culture system, the cells formed a high-grade dysplastic epithelium with malignant cells invading into the stromal extracellular matrix (ECM). The invasive phenotype was in part modulated by the activation of matrix metalloproteinase-9 (MMP-9). Using pharmacological and genetic approaches to decrease MMP-9, invasion into the underlying ECM could be suppressed partially. In addition, tumor differentiation was influenced by the type of fibroblasts within the stromal ECM. To that end, fetal esophageal fibroblasts fostered a microenvironment conducive to poorly differentiated invading tumor cells, whereas fetal skin fibroblasts supported a well-differentiated tumor as illustrated by keratin "pearl" formation, a hallmark feature of well-differentiated squamous cell cancers. When inducible AKT was introduced into fetal skin esophageal fibroblasts, a more invasive, less-differentiated esophageal cancer phenotype was achieved. Invasion into the stromal ECM was attenuated by genetic knockdown of AKT1 as well as AKT2. Taken together, alterations in key oncogenes and tumor suppressor genes in esophageal epithelial cells, the composition and activation of fibroblasts, and the components of the ECM conspire to regulate the physical and biological properties of the stroma. PMID:17974918
Okawa, Takaomi; Michaylira, Carmen Z; Kalabis, Jiri; Stairs, Douglas B; Nakagawa, Hiroshi; Andl, Claudia D; Johnstone, Cameron N; Klein-Szanto, Andres J; El-Deiry, Wafik S; Cukierman, Edna; Herlyn, Meenhard; Rustgi, Anil K
The functional interplay between EGFR overexpression, hTERT activation, and p53 mutation in esophageal epithelial cells with activation of stromal fibroblasts induces tumor development, invasion, and differentiation
Esophageal cancer is a prototypic squamous cell cancer that carries a poor prognosis, primarily due to presentation at advanced stages. We used human esophageal epithelial cells as a platform to recapitulate esophageal squamous cell cancer, thereby providing insights into the molecular pathogenesis of squamous cell cancers in general. This was achieved through the retroviral-mediated transduction into normal, primary human esophageal epithelial cells of epidermal growth factor receptor (EGFR), the catalytic subunit of human telomerase (hTERT), and p53R175H, genes that are frequently altered in human esophageal squamous cell cancer. These cells demonstrated increased migration and invasion when compared with control cells. When these genetically altered cells were placed within the in vivo-like context of an organotypic three-dimensional (3D) culture system, the cells formed a high-grade dysplastic epithelium with malignant cells invading into the stromal extracellular matrix (ECM). The invasive phenotype was in part modulated by the activation of matrix metalloproteinase-9 (MMP-9). Using pharmacological and genetic approaches to decrease MMP-9, invasion into the underlying ECM could be suppressed partially. In addition, tumor differentiation was influenced by the type of fibroblasts within the stromal ECM. To that end, fetal esophageal fibroblasts fostered a microenvironment conducive to poorly differentiated invading tumor cells, whereas fetal skin fibroblasts supported a well-differentiated tumor as illustrated by keratin “pearl” formation, a hallmark feature of well-differentiated squamous cell cancers. When inducible AKT was introduced into fetal skin esophageal fibroblasts, a more invasive, less-differentiated esophageal cancer phenotype was achieved. Invasion into the stromal ECM was attenuated by genetic knockdown of AKT1 as well as AKT2. Taken together, alterations in key oncogenes and tumor suppressor genes in esophageal epithelial cells, the composition and activation of fibroblasts, and the components of the ECM conspire to regulate the physical and biological properties of the stroma.
Okawa, Takaomi; Michaylira, Carmen Z.; Kalabis, Jiri; Stairs, Douglas B.; Nakagawa, Hiroshi; Andl, Claudia; Johnstone, Cameron N.; Klein-Szanto, Andres J.; El-Deiry, Wafik S.; Cukierman, Edna; Herlyn, Meenhard; Rustgi, Anil K.
Eosinophilic esophagitis (EE) is a rarely diagnosed condition involving eosinophilic infiltration of the esophageal mucosa. Here we present a case of EE in a 69-year-old Japanese man, who presented with abdominal pain, appetite loss, and a history of bronchial asthma. Laboratory findings included peripheral eosinophilia and an increased serum immunoglobulin E level. Computed tomography showed diffuse severe thickening of the esophageal wall, and a barium esophagogram revealed a small caliber of the middle and lower portion of the esophagus, without normal peristaltic contractions. Endoscopy of the esophagus showed a pale mucosa, with adherent whitish exudates resembling fungal infection, and prominent ring-like contractions. Histologic examination of a biopsy specimen revealed marked eosinophil infiltration into the esophageal mucosa. Endoscopic ultrasonography (EUS) demonstrated marked circumferential thickening of the esophageal submucosal layer, and an esophageal manometry study showed a high percentage of ineffective esophageal peristalsis and high-amplitude esophageal body contractions. EUS findings showed no change even after oral corticosteroid therapy, although the histological findings were improved. This is thought to be the first documented Japanese case of EE. EE should be considered in the differential diagnosis in cases of esophageal motility disturbance, even if the patients do not complain of dysphagia. PMID:16933010
Furuta, Koichiro; Adachi, Kyoichi; Kowari, Kentaro; Mishima, Yuko; Imaoka, Hiroshi; Kadota, Chikara; Koshino, Kenji; Miyake, Tatsuya; Kadowaki, Yasunori; Furuta, Kenji; Kazumori, Hideaki; Sato, Shuichi; Ishihara, Shunji; Amano, Yuji; Honda, Masaaki; Kinoshita, Yoshikazu
Genes can be introduced into mammary epitheliumin vivo by the ‘tissue reconstitution’ method. Primary cultures of mammary epithelial cells are prepared, a gene introduced using retrovirus vectors, and the cells transplanted into a mammary fat pad from which the normal epithelium has been removed. The cells reform an epithelium in which some cells express the introduced gene. The technique is
Paul A. W. Edwards; Clare L. Abram; Jane M. Bradbury
Perfusion of 0.1 n HC1 5 cm above the lower esophageal sphincter (LES) in cats for 30 min on 4 consecutive days produced biopsy-documented esophagitis and marked decreases in LES pressure. Using this model the effects of experimental esophagitis on the LES response to edrophonium, pentagastrin, and bethanechol were determined. The sphincter response to both edrophonium and pentagastrin after esophagitis was induced was significantly less than preperfusion responses. When the esophagitis had resolved, the pressure response to edrophonium and pentagastrin returned to preperfusion levels. In contrast, the sphincter response to bethanechol during esophagitis was not different from the preperfusion response and remained unchanged after resolution of the esophagitis. Lower esophageal smooth muscle taken from cats with active esophagitis appeared normal by both light and electron microscopy. These studies indicate that besides decreasing resting LES tone, esophageal inflammation causes functional impairment of a cholinergic mechanism regulating LES pressure. In contrast, the smooth muscle appears to be unaffected by inflammation despite the LES hypotension. PMID:1278649
Higgs, R H; Castell, D O; Eastwood, G L
Eosinophilic esophagitis (EoE) is an emerging chronic esophageal disease. Despite the increasing diagnosis of EoE globally, the causes of EoE and other esophageal eosinophilic disorders are not clearly understood. EoE pathology includes accumulation of inflammatory cells (e.g., eosinophils, mast cells), characteristic endoscopic features (e.g., furrows, the formation of fine concentric mucosal rings, exudates), and functional impairments (e.g., esophageal stricture, dysmotility). We hypothesized that the esophageal structural pathology and functional impairments of EoE develop as a consequence of the effector functions of the accumulated inflammatory cells. We analyzed eosinophils (anti-major basic protein immunostaining), esophageal stricture (X-ray barium swallowing), and esophageal motility (isometric force) in two established transgenic murine models of EoE (CD2-IL-5 and rtTA-CC10-IL-13) and a novel eosinophil-deficient model (?dblGATA/CD2-IL-5). Herein, we show the following: 1) CD2-IL-5 and doxycycline (DOX)-induced rtTA-CC10-IL-13 mice have chronic eosinophilic and mast cell esophageal inflammation; 2) eosinophilic esophageal inflammation promotes esophageal stricture in both transgenic murine models; 3) the eosinophil-deficient ?dblGATA/CD-2-IL-5 mice were protected from the induction of stricture, whereas the eosinophil-competent CD2-IL-5 mice develop esophageal stricture; 4) esophageal stricture is not reversible in DOX-induced rtTA-CC10-IL-13 mice (8 wk DOX followed by 8 wk no-DOX); and 5) IL-5 transgene-induced (CD2-IL-5) EoE evidences esophageal dysmotility (relaxation and contraction) that is independent of the eosinophilic esophageal inflammation: CD2-IL-5 and ?dblGATA/CD2-IL-5 mice have comparable esophageal dysmotility. Collectively, our present study directly implicates chronic eosinophilic inflammation in the development of the esophageal structural impairments of experimental EoE.
Mavi, Parm; Rajavelu, Priya; Rayapudi, Madhavi; Paul, Richard J.
Barrett's esophagus (BE) is metaplastic columnar epithelium converted from normal squamous epithelia in the distal esophagus that is thought to be a precancerous lesion of esophageal adenocarcinoma. BE is attributed to gastroesophageal reflux disease (GERD), and therefore gastric acid or bile acids are thought to be factors that cause epithelial cell damage and inflammation in the gastro-esophageal junction. The decrease of adherent junction molecules, E-cadherin has been reported to be associated with the progression of the Barrett's carcinoma, but the initiation of BE is not sufficiently understood. BE is characterized by the presence of goblet cells and occasionally Paneth cells are observed at the base of the crypts. The Paneth cells possess dense granules, in which human antimicrobial peptide human defensin-5 (HD-5) are stored and secreted out of the cells. This study determined the roles of HD-5 produced from metaplastic Paneth cells against adjacent to squamous cells in the gastro-esophageal junction. A human squamous cell line Het-1A, was incubated with the synthetic HD-5 peptide as a model of squamous cell in the gastro-esophageal junctions, and alterations of E-cadherin were investigated. Immunocytochemistry, flowcytometry, and Western blotting showed that the expression of E-cadherin protein was decreased. And a partial recovery from the decrease was observed by treatment with a CD10/neprilysin inhibitor (thiorphan). In conclusion, E-cadherin expression in squamous cells was reduced by HD-5 using in vitro experiments. In gastro-esophageal junction, HD-5 produced from metaplastic Paneth cells may therefore accelerate the initiation of BE. PMID:23958301
Nomura, Yoshiki; Tanabe, Hiroki; Moriichi, Kentaro; Igawa, Satomi; Ando, Katsuyoshi; Ueno, Nobuhiro; Kashima, Shin; Tominaga, Motoya; Goto, Takuma; Inaba, Yuhei; Ito, Takahiro; Ishida-Yamamoto, Akemi; Fujiya, Mikihiro; Kohgo, Yutaka
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.
White, Steven R.
Background and Aim Negative association has been reported between presence of Helicobacter pylori and developing gastroesophageal reflux disease (GERD) and its complications. The aim of this study was to determine whether H. pylori (HP) can be protective against GERD in an African American (AA) population. Methods From 2004 to 2007, we studied 2,020 cases; esophagitis (58), gastritis (1,558), both esophagitis and gastritis (363) and a normal control group (41). We collected their pathology and endoscopy unit reports. HP status was determined based on staining of gastric biopsy. Results HP data was available for 79 % (1,611) of the cases. The frequency of HP positivity in gastritis patients was 40 % (506), in esophagitis patients 4 % and in normal controls 34 % (11), while HP was positive in 34 % of the patients with both esophagitis and gastritis. After adjusting for effects of age and sex, odds ratio of HP was 0.06 (95 % CI 0.01–0.59; P value = 0.01) for the esophagitis group versus the normal group. Conclusions Our results show H. pylori has a significant negative association with esophagitis in AAs which may point to a protective role of H. pylori in the pathogenesis of esophagitis. In addition, H. pylori may be the reason for the low GERD complications in AAs.
Entezari, Omid; Nouraie, Mehdi; Dowlati, Ehsan; Frederick, Wayne; Woods, Alfreda; Lee, Edward; Brim, Hassan; Smoot, Duane T.; Ghadyari, Firoozeh; Kamangar, Farin; Razjouyan, Hadie
\\u000a Purpose: To present the results of a prospective phase II study in esophageal carcinoma.\\u000a \\u000a \\u000a \\u000a Patients and Methods: Patients received single doses of 1.8 Gy up to 27 Gy, then concomitant boost to a total of 50.4 Gy (PTV2 [planning target\\u000a volume], single dose 1.8 Gy) and 64.8 Gy (PTV1, single dose 1.2 Gy in the morning and 1.8 Gy in the afternoon)
Thomas B. Brunner; Andreas Rupp; Winfrid Melzner; Gerhard G. Grabenbauer; Rolf Sauer
Background Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA) were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and molecular pathways mediating ESCC development and provide information potentially useful in designing novel therapeutic interventions for this tumor type.
Esophageal cancer is the 6th leading cause of cancer death worldwide and is associated with a variety of risk factors including tobacco use, heavy alcohol consumption, human papilloma virus infection, and certain dietary factors such as trace mineral and vitamin deficiencies. A connection with ionizing radiation exposure is revealed by the high excess relative risk for esophageal squamous cell carcinoma observed in the survivors of the atomic bomb detonations in Japan. Esophageal carcinomas are also seen as secondary malignancies in patients who received radiotherapy for breast and thoracic cancers; additionally, patients with head/neck and oral squamous cell cancers are at increased risk for metachronous esophageal squamous cell cancers. This malignancy is rapidly fatal, mainly because it remains asymptomatic until late, advanced stages when the disease is rarely responsive to treatment. In normal epithelium, the stromal microenvironment is essential for the maintenance and modulation of cell growth and differentiation. Cross talk between the epithelial and stromal compartments can influence many aspects of malignant progression, including tumor cell proliferation, migration, invasion and recruitment of new blood vessels. To test the hypothesis that radiation exposure plays a role in esophageal carcinogenesis via non-targeted mechanisms involving stromal-epithelial cell communication, we are studying radiation effects on hTERT-immortalized human esophageal epithelial cells and genetic variants grown in co-culture with human esophageal stromal fibrob-lasts (Okawa et al., Genes Dev. 2007. 21: 2788-2803). We examined how irradiation of stromal fibroblasts affected epithelial migration and invasion, behaviors associated with cancer promotion and progression. These assays were conducted in modified Boyden chambers using conditioned media from irradiated fibroblasts. Our results using low LET gamma radiation showed a dose-dependent increase in migration of epithelial cells when exposed to conditioned media from irradiated vs. non-irradiated fibroblasts. We also observed enhanced invasion through a basement membrane matrix in similarly treated cells. Candidate factors that me-diate these effects were identified using antibody capture arrays, and their increased secretion in irradiated fibroblasts was confirmed using ELISAs. We are currently analyzing the effect of these individual factors on epithelial migration and invasion, as well as their influence on cell survival and DNA repair. Our current studies using high-LET radiation will elucidate radiation quality effects on these processes. These results should further our understanding of the mechanisms by which radiation impacts the tissue microenvironment and how it influences cancer development processes.
Huff, Janice; Patel, Zarana; Grugan, Katharine; Rustgi, Anil; Cucinotta, Francis A.
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
Soleas, John P; Paz, Ana; Marcus, Paula; McGuigan, Alison; Waddell, Thomas K
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?B kinases ? (IKK?), 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? 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? (pIKK?) 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? expression was strongly correlated with pS6K1 level. Together, these results show that bile acid can deregulate TSC1/mTOR through IKK? 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.
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
BACKGROUND:Patients with achalasia, diffuse esophageal spasm (DES), and nutcracker esophagus have a thicker muscularis propria than normal subjects. The goal of our study was to determine the prevalence of increased muscle thickness in a group of unselected patients referred to the esophageal function laboratory for evaluation of the symptoms.METHODS:We studied 40 normal subjects and 94 consecutive patients. Manometry and ultrasound
Ibrahim Dogan; James L. Puckett; Bikram S. Padda; Ravinder K. Mittal
Recently, the guidelines for the treatment of gastroesophageal reflux disease (GERD) by the Japanese Society of Gastroenterology. There are many statements including recommended grade (from A to D) and evidence level (from I to VI) for the epidemiology, pathogenesis, diagnosis, medical treatments, surgical treatment of GERD, reflux esophagitis after gastrectomy, and non-typical symptoms of GERD. In this manuscript, we showed the latest date and current status of GERD in Japan used this guidelines. In summary, the prevalence of GERD has been increasing since the end of 1990s, the 1st choice of medical treatment is proton pump inhibitors, endoscopic treatments for GERD are not available in Japan, laparoscopic Toupet fundoplication is superior to laparoscopic Nissen fundoplication as postoperative dysphagia with similar reflux control, and complications of surgical treatment are pneumothorax, splenic injury, aortic injury, gastric ulcer, sever dysphagia, gastric perforation etc., but complication rate is low. PMID:21916192
Omura, Nobuo; Kashiwagi, Hideyuki
If 24-hour esophageal pH monitoring is to be a useful diagnostic tool, it must reliably discriminate gastroesophageal reflux patients despite daily variations in distal esophageal acid exposure. To address this issue, we studied 53 subjects (14 healthy normals, 14 esophagitis patients, and 25 patients with atypical symptoms) with two ambulatory pH tests performed within 10 days of each other. Intrasubject
G. J. Wiener; T. M. Morgan; J. B. Copper; D. O. Castell; J. W. Sinclair; J. E. Richter
Early diagnosis and accurate staging of esophageal cancer are both essential for therapeutic strategy planning. Endoscopic ultrasound, CT, and positron emission tomography have all been used in the preoperative staging of esophageal cancer separately or in various combinations. Each imaging method has its strengths and weaknesses. Depiction of the tumor's anatomic location conditions the surgical strategy. Endoscopic ultrasound and PET have important advantages but neither provides information for surgical planning. CT scans have some limitations for hollow organ assessment in the absence of lumen distension, since the organ wall may be collapsed. Therefore, optimal esophageal distension could be very useful to overcome these limitations. This potential drawback is crucial at the level of the GE junction, a typically difficult region to evaluate. In order to optimize tumor visualization in the esophageal wall and in the GE junction, we developed a technique named pneumo-64-MDCT. We achieve maximum lumen distension, which better highlights the thickened areas in relation to the normal esophageal wall. At the present time, we have performed 200 studies with this technique and it proved useful, safe and accurate to identify esophageal wall thickening and to stage esophageal cancer. The additional stomach distension led to an adequate definition of both the upper and lower borders of the lesion in tumors located in the GE junction, which in turn was helpful to design the surgical approach. PMID:21842399
Ulla, Marina; Gentile, Ernestina María José; Cavadas, Demetrio; Yeyati, Ezequiel Levy; Frank, Laura; Argerich, Javier Ithurralde; Garcia Mónaco, Ricardo
Esophageal manometry is a specialized procedure used to evaluate lower and upper esophageal sphincter pressure, esophageal body contraction amplitude, and peristaltic sequence. The procedure is clinically useful in evaluation of a patient with nonstructural dysphagia, unexplained or noncardiac chest pain, a compendium of symptoms suggested because of gastroesophageal reflux disease, and in the preoperative evaluation for antireflux surgery. Manometric findings in 95 normal subjects evenly distributed across age groups were reported in 1987, and are the values still used in our and most laboratories today. The subsequent review will offer our "view" on the clinical utility of esophageal manometry, on the basis of years of experience and performance techniques that have remained constant over decades. PMID:18364580
Katz, Philip O; Menin, Richard A; Gideon, R Matthew
The factors contributing to the development of esophageal mucosal injury in gastroesophageal reflux disease (GERD) are unclear. The lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and the presence of excessive duodenogastric reflux (DGR) was evaluated in 205 consecutive patients with GERD and various degrees of mucosal injury (no mucosal injury, n = 92; esophagitis, n = 66; stricture, n = 19; Barrett's esophagus, n = 28). Manometry and 24-hour esophageal pH monitoring showed that the prevalence and severity of esophageal mucosal injury was higher in patients with a mechanically defective lower esophageal sphincter (p less than 0.01) or increased esophageal acid/alkaline exposure (p less than 0.01) as compared with those with a normal sphincter or only increased esophageal acid exposure. Complications of GERD were particularly frequent and severe in patients who had a combination of a defective sphincter and increased esophageal acid/alkaline exposure (p less than 0.01). Combined esophageal and gastric pH monitoring showed that esophageal alkaline exposure was increased only in GERD patients with DGR (p less than 0.05) and that DGR was more frequent in GERD patients with a stricture or Barrett's esophagus. A mechanically defective lower esophageal sphincter and reflux of acid gastric juice contaminated with duodenal contents therefore appear to be the most important determinants for the development of mucosal injury in GERD. This explains why some patients fail medical therapy and supports the surgical reconstruction of the defective sphincter as the most effective therapy.
Stein, H J; Barlow, A P; DeMeester, T R; Hinder, R A
In many patients with chest pain of esophageal origin, findings are normal on routine esophageal manometry and dysmotility develops only upon provocation with ergonovine maleate. Unfortunately, ergonovine may induce myocardial ischemia in patients in whom coronary artery spasm did not occur during previous provocative testing in a cardiac laboratory - limiting its clinical usefulness. Esophageal pressure has been recorded simultaneously with ergonovine infusion during angiography in ten patients without significant arterial stenoses. In two patients their usual chest pain developed associated with esophageal spasm and without changes in coronary vessels. Simultaneous performance of angiography and manometry enhanced the diagnostic yield of provocative testing by showing esophageal motility changes. This method may detect significant changes in the esophageal motility, is easy to carry out and does not interfere with angiography. It maximizes the information gained from a single provocative test and avoids the risk of ergonovine infusion outside of a cardiac laboratory.
Lieberman, D.A.; Jendrzejewski, J.W.; McAnulty, J.H.
CD59 (protectin) and CD46 (membrane cofactor protein, MCP) are membrane-bound complement regulator proteins which inhibit complement-mediated cytolysis of autologous cells. CD59, a phosphatidyl-inositol-anchored glycoprotein, inhibits the formation of the terminal membrane attack complex (MAC) of complement and was found to be a second ligand for CD2 contributing to T-cell activation. In 20 colorectal normal mucosa samples, in ten adenomas, 71 carcinomas and in ten liver metastases derived thereof, CD59 was inconsistently expressed in the epithelial compartment. In carcinomas CD59 expression in the whole neoplastic compartment was more often found in well- and moderately differentiated tumours. By contrast, focal expression or even complete lack of CD59 was more often found in poorly differentiated tumours (P = 0.021). In addition, carcinomas without metastases at the time of operation (Dukes A/B) more often expressed CD59 in the entire neoplastic population compared to those carcinomas which had already metastasised (P = 0.018). There was no correlation between the mode of CD59 expression in colorectal carcinomas and the tumour type or location. CD46 has C3b/C4b binding and factor-I dependent cofactor activity and is broadly expressed in various cells and tissues. In the epithelial compartment of normal colorectal mucosa, of all adenomas, carcinomas and their liver metastases, CD46 was expressed throughout the epithelial compartment. Since CD46 was consistently expressed in colorectal carcinomas the low expression or even lack of CD59 in a subset of tumours might not lead to critical complement-mediated attack of CD59-negative tumour cells. Regarding CD59 as a natural T-cell ligand involved in cognate T-cell-target-cell interaction, however, loss of CD59 might well be a selection advantage, provided that tumour antigen-mediated T-cell toxicity in colorectal carcinoma exists. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10
Koretz, K.; Bruderlein, S.; Henne, C.; Moller, P.
In a recent study, a unique gene expression signature was observed when comparing esophageal squamous cell carcinoma (ESCC) epithelial cells to normal esophageal epithelial cells using laser capture microdissection (LCM) and cDNA microarray technology. To validate the expression of several intriguing genes from that study (KRT17, cornulin, CD44, and EpCAM), we employed two new technologies, expression microdissection (xMD) for high-throughput microdissection facilitating protein analysis and RNAscope for the evaluation of low abundant transcripts in situ. For protein measurements, xMD technology was utilized to specifically procure sufficient tumor and normal epithelium from frozen human tissue for immunoblot analysis of KRT17 (CK17) and cornulin. A novel in situ hybridization method (RNAscope) was used to determine the transcript level of two relatively low expressed genes, CD44 and EpCAM in both individual formalin-fixed paraffin-embedded (FFPE) tissue sections and in an ESCC tissue microarray (TMA). The results successfully confirmed the initial expression pattern observed for all four genes, potentially implicating them in the pathogenesis of ESCC. Additionally, the study provides important methodological information on the overall process of candidate gene validation. PMID:23977449
Du, Qiang; Yan, Wusheng; Burton, Victoria H; Hewitt, Stephen M; Wang, Lemin; Hu, Nan; Taylor, Philip R; Armani, Michael D; Mukherjee, Sumana; Emmert-Buck, Michael R; Tangrea, Michael A
A protocol is suggested of complex diagnosis and treatment of Barrett's esophagus using sparing endoscopic removal of Barrett's epithelium in combination with surgery and medicinal antireflux therapy. Eighty-three patients were diagnosed and treated for hernia of esophageal foramen of the diaphragm and gastro-esophageal reflux complicated by Barrett's esophagus. Ninety-two percent of patients receiving our four-component treatment were cured; no recurrent esophageal adenocarcinoma was reported during the 56.7 +/- 2.4 month follow-up. Conversely, in patients receiving three-component treatment, efficacy was 56%; esophageal adenocarcinoma was reported in 3 (12%). PMID:20210013
Burmistrov, M V; Ivanov, A I; Petrov, S V; Akhmetov, T R; Sigal, E I; Murav'ev, V Iu; Moroshek, A A; Broder, I A
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.
Klein-Szanto, A.J.P.; Nettesheim, P.; Pine, A.; Martin, D.
Eosinophilic esophagitis (EE) is a chronic inflammatory disease of the esophagus which is characterized by the presence of dense infiltrate of eosinophilic leukocytes restricted to this organ mucosa. Accumulating published evidence suggests a strong role of mast cells in the inflammatory infiltrate in the physiopathology of EE. We have reviewed published articles with relevant information about the presence and possible role of mast cells in EE. Although mast cells have been studied indirectly in EE, reported data allow us to confirm that the number of mast cells infiltrating the esophageal epithelium in adult and child patients with EE is higher with respect to the normal state and in gastroesophageal reflux disease. Mast cells linked to IgE, which are not found in other conditions, have been identified in EE. Despite that fact, an anaphylactic reaction history after exposure to allergens is not common in these patients. Therefore, the mast cells' function in EE could be dependent on T lymphocytes, as suggested by a mast cell gene expression analysis. Bi-directional crosstalk is established between mast cells and eosinophils, hence establishing interesting hypotheses regarding their relationship to EE physiopathology. Mast cells' function as an immune response leader seems to substitute for their effector functions in EE, while at the same time opening new research pathways for consideration of these cells as a therapeutic target in EE. However, the inefficiency of therapies that inhibit mast cell functions while they are effective in other respiratory tract diseases results in the need for specific studies to identify the real function of such complex cells in the physiopathology of EE. There is indirect proof of the role of mast cells in EE, while many doubts exist about their activation mechanism, which does not seem to be IgE-mediated. Specific approach studies are needed to clarify the function of these cells in the physiopathology of EE, which could be a possible therapeutic target. PMID:18681944
Lucendo, Alfredo J; Bellón, Teresa; Lucendo, Baltasar
Opinion statement Esophageal dilation is the treatment of choice for most patients with esophageal dysphagia (functional and mechanical). Multiple\\u000a forms of esophageal dilators are available. Mechanical dilators (guidewire\\/nonguidewire assisted) are the major forms of dilators\\u000a used. Balloon dilator use has increased but they offer only a marginal advantage over traditional mechanical dilators at a\\u000a greatly increased cost (2° to single use).
Timothy T. Nostrant
In order to asses whether in reflux esophagitis morphological and functional disorders persist after macroscopic healing, cimetidine was given for 6–12 weeks at a dose of 1.6 g\\/day to 30 patients with acid gastroesophageal reflux and esophagitis. The mucosal defects healed in 6 patients, improved in 14 patients, and remained unchanged in 10 patients. Lower esophageal sphincter pressure, acid clearance,
Amnon Sonnenberg; Gerd Lepsien; STEFAN A. MISILLER-LISSNER; Hans R. Koelz; J. Rüdiger Siewert; André L. Blum
The incidence of esophageal cancer is increasing. Worldwide it is the ninth most common malignancy and is endemic in many\\u000a parts of the world, particularly in the developing countries. There were 14,550 new cases and 13,770 deaths from esophageal\\u000a cancer in the United States in 2006. Esophageal cancer has two pathological subtypes: squamous cell carcinoma and adenocarcinoma.\\u000a Squamous cell carcinoma
Lana Y. Schumacher; Nicole B. Baril; Sherry M. Wren
Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.
Fujimura, Takashi; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo; Koichi, Miwa; Takanori, Hattori
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.
Orlando, Roy C.
Objectives: The aims of this study were to develop a new method for analysis and presentation of esophageal distensibility data using high-resolution impedance planimetry recordings during a volume-controlled distention. Methods: Two control subjects and six patients with eosinophilic esophagitis (EoE) with stricture, narrow caliber or normal endoscopy according to EndoFLIP studies were included for analysis. Median filtering and pulse detection techniques were applied to the pressure signal and a wavelet decomposition technique was applied to the 16 channels of raw esophageal diameter data to reduce vascular artifact, respiratory effect and remove esophageal contraction interference. These data were used to generate a functional luminal imaging probe (FLIP) topography plot that describes regional variation of cross-sectional area (CSA). A previously developed computer program was used to calculate and model the CSA-pressure data to derive the slope of line fitting and distension plateau for each individual subject. The results were compared among the four endoscopic phenotypes. Results: Patients with EoE and normal endoscopy had similar esophageal distensibility parameters to those of normal controls whereas patients with EoE and stricture or narrow caliber had much lower distensibility than patients with EoE and normal endoscopy. The FLIP topography plots provided a global assessment of the esophageal distensibility along the axial plane of measurement that differentiated patients with varying degrees of endoscopic abnormality. Conclusions: New techniques can be leveraged to improve data analysis and presentation using EndoFLIP assessment of the esophageal body in EoE. These techniques may be helpful in defining clinically relevant phenotypes and guiding treatment strategies and should be helpful in structuring future outcome trials.
Kahrilas, Peter J.; Xiao, Yinglian; Nicodeme, Frederic; Gonsalves, Nirmala; Hirano, Ikuo; Pandolfino, John E.
Rat and human biliary epithelium is morphologically and functionally heterogeneous. As no information exists on the heterogeneity of the murine intrahepatic biliary epithelium, and with increased usage of transgenic mouse models to study liver disease pathogenesis, we sought to evaluate the morphological, secretory, and proliferative phenotypes of small and large bile ducts and purified cholangiocytes in normal and cholestatic mouse
Shannon S Glaser; Eugenio Gaudio; Arundhati Rao; Lisa M Pierce; Paolo Onori; Antonio Franchitto; Heather L Francis; David E Dostal; Julie K Venter; Sharon DeMorrow; Romina Mancinelli; Guido Carpino; Domenico Alvaro; Shelley E Kopriva; Jennifer M Savage; Gianfranco D Alpini
The functional esophageal disorders include globus, rumination syndrome, and symptoms that typify esophageal diseases (chest pain, heartburn, and dysphagia). Factors responsible for symptom production are poorly understood. The criteria for diagnosis rest not only on compatible symptoms but also on exclusion of structural and metabolic disorders that might mimic the functional disorders. Additionally, a functional diagnosis is precluded by the presence of a pathology-based motor disorder or pathological reflux, defined by evidence of reflux esophagitis or abnormal acid exposure time during ambulatory esophageal pH monitoring. Management is largely empirical, although efficacy of psychopharmacological agents and psychological or behavioral approaches has been established for serveral of the functional esophageal disorders. As gastroesophageal reflux disease overlaps in presentation with most of these disorders and because symptoms are at least partially provoked by acid reflux events in many patients, antireflux therapy also plays an important role both in diagnosis and management. Further understanding of the fundamental mechanisms responsible for symptoms is a priority for future research efforts, as is the consideration of treatment outcome in a broader sense than reduction in esophageal symptoms alone. Likewise, the value of inclusive rather than restrictive diagnostic criteria that encompass other gastrointestinal and non-gastrointestinal symptoms should be examined to improve the accuracy of symptom-based criteria and reduce the dependence on objective testing.???Keywords: globus; rumination; chest pain; esophageal motility disorders; esophageal spasm; gastroesophageal reflux disease; Rome II
Clouse, R; Richter, J; Heading, R; Janssens, J; Wilson, J
... they can bleed severely. Any type of chronic liver disease can cause esophageal varices. Varices can also occur ... People with chronic liver disease and esophageal varices may have no symptoms. If there is only a small amount of bleeding, the only symptom ...
Eosinophilic esophagitis and eosinophilic gastroenteritis is being recognized more frequently among the adult patients. The disease is characterized by massive infiltration of the wall of gastrointestinal tract by sheets of eosinophils. The clinical features depend upon the site of involvement. They include dyspepsia, dysphagia, nausea, vomiting, chest pain, diarrhea and protein-losing enteropathy. Eosinophilic esophagitis may present as chest pain, dysphagia or dyspepsia. The characteristic endoscopic feature of eosinophilic esophagitis is the formation of fine concentric mucosal rings (corrugated esophagus). Regarding the pathogenesis of these mucosal rings our hypothesis is that mast cells in the esophageal wall in response to allergens release histamine, eosinophilic chemotactic factor and platelet activating factor, etc. which activate eosinophils to release toxic cationic proteins. Activation of acetyl choline by histamine may cause contraction of the muscle fibers in the muscularis mucosae resulting in the formation of esophageal rings. This hypothesis can be tested by demonstrating the contraction of muscle layers of muscularis mucosae with the use of high frequency endoscopic ultrasonic probe introduced via the biopsy channel of an endoscope. PMID:15617859
Mann, N S; Leung, J W
Delta-aminolevulinic acid / protoporphyrin IX is applied for exogenous fluorescent tumor detection in the upper part of gastrointestinal tract. The 5-ALA is administered per os six hours before measurements at dose 20mg/kg weight. Highpower light-emitting diode at 405 nm is used as a source and the excitation light is passed through the light-guide of standard video-endoscopic system to obtain 2-D visualization. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. In such way 1-D detection and 2-D visualization of the lesions' fluorescence are received. The results from in vivo detection show significant differentiation between normal and abnormal tissues in 1-D spectroscopic regime, but only moderate discrimination in 2-D imaging. In the case of 2-D video visualization the problem of relatively high levels of the autofluorescence signal in the red spectral region gives low contrast between normal and abnormal mucosa when standard CCD camera of the endoscope is applied. Sensitized inflammatory areas also give to the observer in 2-D mode low contrast between malignant areas and benign tissues and finally the emission signals are additionally altered from the re-absorption of the chromophores accumulated in the tissue investigated. The possibilities for proper discrimination between normal, inflammatory and malignant tissues using 5-ALA/PpIX and both - advantages and limitations of 1-D and 2-D fluorescent detection modes are discussed in relation to their clinical applicability.
Borisova, Ekaterina; Vladimirov, Borislav; Avramov, Lachezar
Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remod- eling. Hence, we hypothesized that after injury the airway epithe- lium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air-liquid interface were co-cultured with serum-deprived normal
Nikita K. Malavia; Christopher B. Raub; Sari B. Mahon; Matthew Brenner; Reynold A. Panettieri; Steven C. George
The electrolyte transport system across human airway epithelium followed by water movement is essential for the normal mucociliary clearance that allows the maintenance of the aseptic condition of the respiratory tract. The function of epithelial cells is to control and regulate ionic composition and volume of fluids in the airways. Various types of proteins taking part in assuring effective ions and water transport in apical and basolateral membranes of the airway epithelium have been found (e.g., CFTR, ENaC, CaCC, ORCC, potassium channels, NaKATPase, aquaporins). The paper reviews the current state of the art in the field of ion channels, transporters, and other signaling proteins identified in the human bronchial epithelium. PMID:21975871
Toczy?owska-Mami?ska, Renata; Do?owy, Krzysztof
Thrnmbnmodulin i'l Mi Â¡s thrombin receptor that was identified orig inally on the endothelium and acts as a natural anticoagulant. However, we reported previously that TM was also expressed in the squamous epithelium mainly at the intercellular bridges. In this study, we examined TM expression in the primary lesions of 106 patients with esophageal squamous cell carcinomas and in the
Yoshihisa Tezuka; Suguru Yonezawa; Ikuro Maruyama; Yoshifumi Matsushita; Takeshi Shimizu; Hiroya Obama; Mitsuhisa Sagar; Kazusada Shirao; Chikara Kusano; Shoji Natsugoe; Heiji Yoshinaka; Masamichi Baba; Toshitaka Fukumoto; Takashi Aikou; Eiichi Sato
Metastatic involvement (59.2%) was noted in esophageal cancer during autopsy on 710 cases, with lymphogenic metastasis predominating over hematogenic metastasis. In those dying soon after radiation therapy there were metastasis in 49% and in 30% after sur...
A. I. Pirogov V. D. Ryndin
... the type of cells that become malignant (cancerous): Squamous cell carcinoma : Cancer that begins in squamous cells , the thin, ... chance of developing esophageal cancer increases with age. Squamous cell carcinoma of the esophagus is more common in blacks ...
Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals...
M. E. Rothenberg
Eosinophilic esophagitis (EE) is an emerging worldwide food allergic disorder associated with polysensitization to multiple food allergens, resulting in greatly restricted diets and chronic gastroesophageal reflux disease-like symptoms in many individuals...
Diffuse esophageal spasm (DES) causes chest pain and/or dysphagia in adults. We reviewed charts of 278 subjects 0 to 18 years of age after esophageal manometry to describe the frequency and characteristics of DES in children. Patient diagnoses included normal motility (61%), nonspecific esophageal motility disorder (20%), DES (13%, n=36), and achalasia (4%). Of patients with DES, the most common chief complaint was food refusal in subjects younger than 5 years (14/24, 58%) and chest pain in subjects older than 5 years (4/12, 33%). Comorbid medical conditions, often multiple, existed in 33 subjects. DES should be considered when young children present with food refusal. PMID:23114472
Rosen, John M; Lavenbarg, Teri; Cocjin, Jose; Hyman, Paul E
Esophageal carcinoma is the fifth most common gastrointestinal cancer, and the recent data suggests that it is rising in incidence\\u000a faster than any other malignancy. Although esophageal carcinoma is generally felt to have a poor prognosis, this is largely\\u000a owing to the heterogeneity of patients. As with any malignancy, the stage of the tumor predicts prognosis and determines treatment\\u000a options.
Jason Vollweiler; Gregory Zuccaro
We report that matrilysin, a matrix metalloproteinase, is constitutively expressed in the epithelium of peribronchial glands and conducting airways in normal lung. Matrilysin expression was increased in airway epithelial cells and was induced in alveolar type II cells in cystic fibrosis. Other metalloproteinases (collagenase-1, stromelysin-1, and 92-kD gelatinase) were not produced by normal or injured lung epithelium. These observations suggest that matrilysin functions in injury-mediated responses of the lung. Indeed, matrilysin expression was increased in migrating airway epithelial cells in wounded human and mouse trachea. In human tissue, epithelial migration was reduced by > 80% by a hydroxamate inhibitor, and in mouse tissue, reepithelialization in trachea from matrilysin-null mice was essentially blocked. In vivo observations and cell culture studies demonstrated that matrilysin was secreted lumenally by lung epithelium, but upon activation or while migrating over wounds, some matrilysin was released basally. The constitutive production of matrilysin in conducting airways, its upregulation after injury, its induction by alveolar epithelium, and its release into both lumenal and matrix compartments suggest that this metalloproteinase serves multiple functions in intact and injured lung, one of which is to facilitate reepithelialization. PMID:9769324
Dunsmore, S E; Saarialho-Kere, U K; Roby, J D; Wilson, C L; Matrisian, L M; Welgus, H G; Parks, W C
BackgroundGastroesophageal reflux is a frequent problem after esophageal atresia (EA) repair. Our aim was to determine the prevalence of esophagitis and Barrett esophagus more than 10 years after repair of EA.
Jacqueline A. Deurloo; Seine Ekkelkamp; Jan A. J. M. Taminiau; C. M. Frank Kneepkens; Fibo W. J. ten Kate; Joep F. W. M. Bartelsman; Dink A. Legemate; Daniel C. Aronson
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.
Maddern, G.J.; Horowitz, M.; Jamieson, G.G.; Chatterton, B.E.; Collins, P.J.; Roberts-Thomson, P.
The esophagus is a hollow muscular tube with ends closed proximally and distally by muscular sphincters. The upper esophageal sphincter and proximal one third of the esophageal body are composed of striated muscle. There is then a transition zone where striated and smooth muscle mix together. The lower esophageal sphincter and the distal one half to two thirds of the
The authors report the case of lower carvical\\/ upper thoracic esophageal duplication associated with an obstructing esophageal web. This presented in the newborn period as an esophageal atresia. Initial resection of the web and closure of the fistula were performed. The duplication was excised electively at 2 months of age. Persistent symptomatic tracheomalacia required aortopexy, after which the child recovered
Charles L Snyder; Steven W Bickler; George K Gittes; V Ramachandran; Keith W Ashcraft
This article reviews the current management of esophageal cancer, including staging and treatment options, as well as providing support for using multidisciplinary teams to better manage esophageal cancer patients. PMID:23453332
Mulligan, Charles R
... tests to evaluate for achalasia and other esophageal motility disorders is manometry. This test is performed on an outpatient basis. A small ... coordination of contractions of the esophageal muscles. Some motility disorders, including ... TREATMENTS ARE AVAILABLE FOR ACHALASIA? Endoscopic Treatment ...
MENU Return to Web version Esophageal Atresia and Tracheoesophageal Fistula Overview What is esophageal atresia? In babies who ... swallows gets into the stomach. What is a tracheoesophageal fistula? A fistula (say “fist-you-lah”) is a ...
Purpose Albuterol reduces lower esophageal sphincter (LES) pressure in normal volunteers, although the effects of albuterol on esophageal\\u000a function in asthmatic patients are not known. The aim of this study was to evaluate the effects of nebulized albuterol on\\u000a lower esophageal function in asthmatic patients. Symptoms and a methacholine challenge test were used to identify asthmatic\\u000a patients who were then
Brian E. Lacy; Carole Mathis; John DesBiens; Mark C. Liu
Early esophageal cancer is defined as a tumor invading the mucosa with or without lymph node or distant organ metastasis. In the current guidelines for early esophageal cancer, absolute indication for endoscopic resection include lesions limited to the epithelium or lamina propria mucosa not exceeding two-thirds of the circumference, and relative indications include lesions limited to the muscularis mucosa or the upper third of the submucosal layer and not accompanied by clinical evidence of lymph node metastasis. After endoscopic submucosal dissection for early esophageal cancer, locally recurrent cancer can occur, especially in the case of incomplete resection. Here, we report a rare case of a submucosal tumor-like recurrence after endoscopic resection of early esophageal cancer.
Choi, Jeong Cheon; Park, Do Youn; Seoung, Hyeog Gyu; Lee, Yong Jae; Kim, Ji Hye; Kim, Tae Kyun; I, Hoseok
Esophageal perforation is usually an acute, life-threatening event, and its diagnosis can be established on the basis of obvious clinical and radiographic findings. This article describes two cases whereby symptoms of esophageal perforations were masked by concomitant administration of steroids, thus causing marked delay in diagnosis and treatment. Esophageal rupture should be considered when patients receiving steroids develop unexplained fever
Linas M. Klygis; Rome Jutabha; Michael B. McCrohan; Arvydas D. Vanagunas
The esophageal epithelium is a prototypical stratified squamous epithelium that exhibits an exquisite equilibrium between proliferation and differentiation. After basal cells proliferate, they migrate outward toward the luminal surface, undergo differentiation, and eventually slough due to apoptosis. The identification and characterization of stem cells responsible for the maintenance of the esophageal epithelium remains elusive. Here, we employed Hoechst dye extrusion and BrdU label-retaining assays to identify in mice a potential esophageal stem cell population that localizes to the basal cell compartment. The self-renewing capacity of this population was characterized using a clonogenic assay and a 3D organotypic culture model. The putative esophageal stem cells were also capable of epithelial reconstitution in vivo in direct esophageal epithelial injury models. In both the 3D organotypic culture and direct mucosal injury models, the putative stem cells gave rise to undifferentiated and differentiated cells. These studies therefore provide a basis for understanding the regenerative capacity and biology of the esophageal epithelium when it is faced with injurious insults. PMID:19033657
Kalabis, Jiri; Oyama, Kenji; Okawa, Takaomi; Nakagawa, Hiroshi; Michaylira, Carmen Z; Stairs, Douglas B; Figueiredo, Jose-Luiz; Mahmood, Umar; Diehl, J Alan; Herlyn, Meenhard; Rustgi, Anil K
Background High expression of Bmi-1, a key regulatory component of the polycomb repressive complex-1, has been associated with many solid and hematologic malignancies including esophageal squamous cell carcinoma. However, little is known about the role of Bmi-1 in esophageal adenocarcinoma. The aim of this study is to investigate the amplification and high expression of Bmi-1 and the associated clinicopathologic characteristics in esophageal adenocarcinoma and squamous cell carcinoma. Methods The protein expression level of Bmi-1 was detected by immunohistochemistry (IHC) from tissue microarrays (TMA) constructed at the University of Rochester from using tissues accrued between 1997 and 2005. Types of tissues included adenocarcinoma, squamous cell carcinoma and precancerous lesions. Patients’ survival data, demographics, histologic diagnoses and tumor staging data were collected. The intensity (0–3) and percentage of Bmi-1 expression on TMA slides were scored by two pathologists. Genomic DNA from 116 esophageal adenocarcinoma was analyzed for copy number aberrations using Affymetrix SNP 6.0 arrays. Fisher exact tests and Kaplan-Meier methods were used to analyze data. Results By IHC, Bmi-1 was focally expressed in the basal layers of almost all esophageal squamous mucosa, which was similar to previous reports in other organs related to stem cells. High Bmi-1 expression significantly increased from squamous epithelium (7%), columnar cell metaplasia (22%), Barrett’s esophagus (22%), to low- (45%) and high-grade dysplasia (43%) and adenocarcinoma (37%). The expression level of Bmi-1 was significantly associated with esophageal adenocarcinoma differentiation. In esophageal adenocarcinoma, Bmi-1 amplification was detected by DNA microarray in a low percentage (3%). However, high Bmi-1 expression did not show an association with overall survival in both esophageal adenocarcinoma and squamous cell carcinoma. Conclusions This study demonstrates that high expression Bmi-1 is associated with esophageal adenocarcinoma and precancerous lesions, which implies that Bmi-1 plays an important role in early carcinogenesis in esophageal adenocarcinoma.
The diagnosed multiple cancer cases have recently been increasing in number. The frequency of synchronous esophageal and gastric carcinomas is increasing due to development of more sophisticated invasive and non-invasive diagnostic tools and an increase in the number of elderly patients. Four cases of synchronous esophageal and gastric cancers were diagnosed in 2nd Department of Radiology, Medical University of Lublin and in Radiological Department of Hospital in Krosno between the 1996 and 2002. In all cases double-contrast barium examinations of upper gastrointestinal tract were performed. In all cases the two lesions were found, separated by normal mucous membrane. In two cases the irregular tumor masses were localized in the gastric cardia. In two patients coexistent lesions form the oval filling defect, with hazy appearance in the middle of the anterior esophageal wall. In three cases the results of contrast examinations were confirmed with CT. Endoscopy with taking the specimens for histopathological examination supplemented the radiological examination. The results of histopathological examinations confirmed the diagnosis. The possibility of multiple primary cancers should be kept in mind during the preoperative examination. In case of esophageal cancer with severe stricture, when endoscope cannot be passed through the esophagus, the stomach should be carefully examined in a barium meal study. PMID:16146021
Pas?awski, Marek; Z?omaniec, Janusz; Ruci?ska, Eulalia; Ko?ty?, Witold
Retinal pigment epithelium (RPE) arises from neuroectoderm and plays a key role in support of photoreceptor functions. Several degenerative eye diseases, such as macular degeneration or retinitis pigmentosa, are associated with impaired RPE function that may lead to photoreceptor loss and blindness. RPE derived from human embryonic stem (hES) cells can be an important source of this tissue for transplantation to cure such degenerative diseases. This chapter describes differentiation of hES cells to RPE, its subsequent isolation, maintenance in culture, and characterization. PMID:17141036
Advanced esophageal carcinoma has poor prognosis with 5-year survival of less than 20%. This poor prognosis is the same for squamous cell carcinoma and adenocarcinoma. Surgical therapy, external radiation and chemotherapy with curative intent are usually impossible because of the advanced disease. Dysphagia is the most frequent symptom affecting quality of life. Bougies or balloon dilation improves dysphagia only short-term (few days). Nd-YAG laser, ACP and photodynamic therapy all have mid-range effect and require repetition after few weeks. Brachytherapy and esophageal self-expanding stent insertion have longer benefit. Stent insertion provides fastest improvement of dysphagia; however, complications in later setting occur in30% and require further endoscopic treatment. Brachytherapy has slower onset of benefit but has fewer complications and longer benefit. Brachytherapy is suitable for patients wit expected lifespan more than 3 months. Most important contraindication of brachytherapy is tracheo-esophageal fistula. PMID:19202963
The intelligibility of esophageal speech has been shown to be significantly lower than that of normal laryngeal speech. The current study investigated the possibility of enhancing the intelligibility of esophageal speech by manipulating samples in the time domain. Specifically, injection noises and nonphrasal pauses were digitally edited from the speech samples of 5 esophageal talkers. Twenty-five sentences were selected and edited in the time domain and presented to 15 naive listeners who were instructed to write down the words that they heard. The percentage of correct words heard for each sentence was determined and compared across listeners, sentences, and talkers. The overall effect of the editing was a small but significant gain in the intelligibility of the esophageal speech. The improvement in intelligibility, however, depended on the individual talker, the speech material, and the number of editing changes made to a particular sample. PMID:11407558
Prosek, R A; Vreeland, L L
Objective: To evaluate the outcome of aggressive conservative therapy in patients with esophageal perforation. Summary Background Data: The treatment of esophageal perforation remains controversial with a bias toward early primary repair, resection, and/or proximal diversion. This review evaluates an alternate approach with a bias toward aggressive drainage of fluid collections and frequent CT and gastographin UGI examinations to evaluate progress. Methods: From 1992 to 2004, 47 patients with esophageal perforation (10 proximal, 37 thoracic) were treated (18 patients early [<24 hours], 29 late). There were 31 male and 16 females (ages 18–90 years). The etiology was iatrogenic (25), spontaneous (14), trauma (3), dissecting thoracic aneurysm (3), and 1 each following a Stretta procedure and Blakemore tube placement. Results: Six of 10 cervical perforations underwent surgery (3 primary repair, 3 abscess drainage). Nine of 10 perforations healed at discharge. In 37 thoracic perforations, 2 underwent primary repair (1 iatrogenic, 1 spontaneous) and 4 underwent limited thoracotomy. Thirty-4 patients (4 cervical, 28 thoracic) underwent nonoperative treatment. Thirteen of the 14 patients with spontaneous perforation (thoracic) underwent initial nonoperative care. Overall mortality was 4.2% (2 of 47 patients). These deaths represent 2 of 37 thoracic perforations (5.4%). There were no deaths in the 34 patients treated nonoperatively. Esophageal healing occurred in 43 of 45 surviving patients (96%). Subsequent operations included colon interposition in 2, esophagectomy for malignancy in 3, and esophagectomy for benign stricture in 2. Conclusions: Aggressive treatment of sepsis and control of esophageal leaks leak lowers mortality and morbidity, allow esophageal healing, and avoid major surgery in most patients.
Vogel, Stephen B.; Rout, W Robert; Martin, Tomas D.; Abbitt, Patricia L.
Abnormalities in esophageal peristaltic function and acid clearance appear to be responsible for prolonged esophageal acid exposure, a major determinant of the reflux esophagitis and esophageal stricture. We evaluated esophageal motility by manometry in 50 healthy controls and in 35 symptomatic reflux patients before, within 6 months, and 1 year after Nissen fundoplication. Preoperative motility was analyzed in relation to the presence or absence of both nonobstructive dysphagia and erosive esophagitis. We found that (a) preoperative dysphagia was related more to peristaltic dysfunction than to esophagitis; (b) peristaltic wave amplitude and duration were significantly lower than control values in patients with reflux, without correlation to degree of esophagitis or lower esophageal sphincter hypotension; (c) dysphagia ceased in most patients after antireflux surgery at the same time that normal motility was restored independently of lower esophageal sphincter pressure increments. These results suggest that motility disturbances are an important cause of dysphagia in reflux disease, and that reflux is the cause of, rather than the consequence of, peristaltic dysfunction. PMID:2007730
Grande, L; Lacima, G; Ros, E; Pujol, A; Garcia-Valdecasas, J C; Fuster, J; Visa, J; Pera, C
OBJECTIVE--To determine whether tobacco smoking causes increased DNA modification (adducts) in human cervical epithelium. DESIGN--Comparison of DNA adducts measured by the technique of postlabelling with phosphorus-32 in normal ectocervical epithelium of smokers and non-smokers. A questionnaire on smoking habit and a urinary cotinine assay were used to identify smokers and non-smokers. SETTING--Cytology unit in large teaching hospital. SUBJECTS--39 women (11
A M Simons; D H Phillips; D V Coleman
Gingival innate immunity has been studied by using biopsies and normal or transformed epithelial cell monolayers. To overcome\\u000a individual biological variabilities and as a physiological alternative, we have proposed using a reconstructed tissue equivalent.\\u000a In this study, we investigated the functionality and the stage of differentiation of a reconstructed human gingival epithelium.\\u000a We also characterized this epithelium at the molecular
A. Peyret-Lacombe; H. Duplan; M. Watts; M. Charveron; G. Brunel
Acute esophageal necrosis (AEN), commonly referred to as “black esophagus”, is a rare clinical entity arising from a combination of ischemic insult seen in hemodynamic compromise and low-flow states, corrosive injury from gastric contents in the setting of esophago-gastroparesis and gastric outlet obstruction, and decreased function of mucosal barrier systems and reparative mechanisms present in malnourished and debilitated physical states. AEN may arise in the setting of multiorgan dysfunction, hypoperfusion, vasculopathy, sepsis, diabetic ketoacidosis, alcohol intoxication, gastric volvulus, traumatic transection of the thoracic aorta, thromboembolic phenomena, and malignancy. Clinical presentation is remarkable for upper gastrointestinal bleeding. Notable symptoms may include epigastric/abdominal pain, vomiting, dysphagia, fever, nausea, and syncope. Associated laboratory findings may reflect anemia and leukocytosis. The hallmark of this syndrome is the development of diffuse circumferential black mucosal discoloration in the distal esophagus that may extend proximally to involve variable length of the organ. Classic “black esophagus” abruptly stops at the gastroesophageal junction. Biopsy is recommended but not required for the diagnosis. Histologically, necrotic debris, absence of viable squamous epithelium, and necrosis of esophageal mucosa, with possible involvement of submucosa and muscularis propria, are present. Classification of the disease spectrum is best described by a staging system. Treatment is directed at correcting coexisting clinical conditions, restoring hemodynamic stability, nil-per-os restriction, supportive red blood cell transfusion, and intravenous acid suppression with proton pump inhibitors. Complications include perforation with mediastinal infection/abscess, esophageal stricture and stenosis, superinfection, and death. A high mortality of 32% seen in the setting of AEN syndrome is usually related to the underlying medical co-morbidities and diseases.
Gurvits, Grigoriy E
This paper presents commentaries on whether eosinophilic esophagitis is a food allergy; inflammation in the context of eosinophilic esophagitis; whether eosinophilic esophagitis a cause of noncardiac chest pain; the role of endoscopy in the evaluation of eosinophilic esophagitis; and whether response to proton pump inhibitor therapy can distinguish eosinophilic esophagitis from gastroesophageal reflux disease. PMID:24117638
Chehade, Mirna; Lucendo, Alfredo J; Achem, Sami R; Souza, Rhonda F
Alpha-fetoprotein (AFP)-producing esophageal tumors are extremely rare. We report herein the case of a 51-year-old man found to have an AFP-producing adenocarcinoma arising from esophageal proper mucosa. The patient presented for investigation of dysphagia, and esophagogram and endoscopy revealed a lesion about 2 cm in size with a depressed center surrounded by low nodular protrusions in the lower esophagus. The preoperative serum AFP concentration was elevated to 52.4 ng/ml. A subtotal esophagectomy was performed, and macroscopic examination of the resected specimen revealed a superficial protruding lesion. Histopathological studies showed a poorly differentiated adenocarcinoma with a single lymph node metastasis. The tumor had infiltrated the submucosal layer, but there was no evidence of lymphatic or venous invasion. Immunohistochemical study revealed tumor cells positive for AFP. There were no findings of Barrett's epithelium or any mucosal changes due to reflux esophagitis. An elevated AFP level 2 years after the operation led us to suspect tumor recurrence; however, diagnostic imaging studies showed no evidence of a recurrence or metastases. The serum AFP levels responded well to chemotherapy with transient decreased levels, but continued to rise until finally, 5 years after the operation, adenocarcinoma cells were detected in the pleural effusion. Thus, careful monitoring of the serum AFP levels at regular intervals could be a useful marker to indicate recurrence of esophageal carcinoma. PMID:11759890
Kobayashi, N; Ohbu, M; Kuroyama, S; Kikuchi, S; Shimao, H; Mitomi, H; Kakita, A
Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro.
Abstract Background and aims. Gastroesophageal reflux disease (GERD) is associated with impaired epithelial barrier function. However, the influence of acid and/or bile acids on human esophageal epithelial barrier function and the tight junction (TJ) proteins has not been fully elucidated. The aim of the study is to investigate the esophageal barrier function and TJ expression in healthy subjects and patients with GERD. The functionality of esophageal mucosa exposed to bile salt deoxycholic acid (DCA) and trypsin has been studied in vitro. Material and methods. Endoscopic biopsies from healthy controls and patients with GERD-related symptom with endoscopic erosive signs, as well as esophageal mucosa taken from patients undergoing esophagectomy were evaluated in Ussing chambers and by western blot and immunohistochemistry. Results. The esophageal epithelium from GERD patients had lower electrical resistance and higher epithelial currents than controls. Claudin-1 and -4 were significantly decreased in GERD patients. The bile salt DCA in the low concentration of 1.5 mM and trypsin increased the resistance and claudin-1 expression, while the higher concentration of 2.5 mM DCA and trypsin decreased the resistance and the claudin-3, -4 and E-cadherin expressions. Conclusion. In addition to acidic reflux, duodenal reflux components, such as bile salts and trypsin, have the potential to disrupt the esophageal barrier function, partly by modulating the TJ proteins. However, the expression of TJ is dependent on both the refluxed material as well as the concentration of the bile salt. PMID:24047393
Björkman, Eleonora Victoria Charlotta; Edebo, Anders; Oltean, Mihai; Casselbrant, Anna
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.
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. PMID:10761701
Kawabata, K; Tanaka, T; Yamamoto, T; Ushida, J; Hara, A; Murakami, A; Koshimizu, K; Ohigashi, H; Stoner, G D; Mori, H
Spontaneous esophageal rupture is an uncommon and poorly understood condition. Recurrent rupture is extremely rare, with only one previously reported case in the literature. Here, we present a case series of two patients who had recurrent ruptures, and discuss the principles underlying the management of such cases.
Omar A. Khan; Clifford W. Barlow; David F. Weeden; Khalid M. Amer
Herpes simplex virus esophagitis has rarely been reported in immunocompetent children. We describe 2 immunocompetent wrestlers on the same team who presented with fever, odynophagia, and dysphagia. Histologic examination of the esophagus showed ulceration and exudate, herpes simplex virus was detected by polymerase chain reaction. We propose that wrestling may be a mode of transmission for this disease. PMID:21544004
Khlevner, Julie; Beneri, Christy; Morganstern, Jeffrey A
Esophageal cancer (EsC) is one of the least studied and deadliest cancers worldwide because of its extremely aggressive nature and poor survival rate. It ranks sixth among all cancers in mortality. In retrospective studies of EsC, smoking, hot tea drinking, red meat consumption, poor oral health, low intake of fresh fruit and vegetables, and low socioeconomic status have been associated with a higher risk of esophageal squamous cell carcinoma. Barrett’s esophagus is clearly recognized as a risk factor for EsC, and dysplasia remains the only factor useful for identifying patients at increased risk, for the development of esophageal adenocarcinoma in clinical practice. Here, we investigated the epidemiologic patterns and causes of EsC. Using population based cancer data from the Surveillance, Epidemiology and End Results Program of the United States; we generated the most up-to-date stage distribution and 5-year relative survival by stage at diagnosis for 1998-2009. Special note should be given to the fact that esophageal cancer, mainly adenocarcinoma, is one of the very few cancers that is contributing to increasing death rates (20%) among males in the United States. To further explore the mechanism of development of EsC will hopefully decrease the incidence of EsC and improve outcomes.
... determine if you have a ring or a web, your doctor may order one of these tests: Barium swallow test. This allows the radiologist to ... contribute to the development of esophageal rings and webs, your doctor probably will order a blood test for iron levels and, if you are deficient, ...
The distribution of a range of integrins, E-cadherin, and carcino-embryonic antigen (CEA) like molecules in normal human oesophageal epithelium was investigated immunohistochemically on frozen sections of endoscopic biopsy specimens. The integrin subunits alpha 2, alpha 3, alpha 6, alpha v, beta 1, and beta 5 were expressed throughout the epithelium. There was strong expression of alpha 2, alpha 3, and beta 1 subunits in the basal cell layer and for all the subunits studied the intensity of the staining decreased as cells moved towards the lumen. The heterodimer alpha v beta 3 was expressed weakly in the basal aspect of the basal cell layer only. The CEA molecules were not present in the basal cells layer but there was weak expression in the prickle cell layer and strong positivity in the mature functional layer. E-cadherin was found throughout the epithelium but was weakly expressed at the basal aspect of the basal cells layer and showed strong positivity in the prickle cell and squamous cell layers. These results indicate that cell-cell (E-cadherin, CEA) and cell-matrix (integrins) adhesion molecules show a well defined spatial pattern of immunoreactivity in the oesophageal mucosa and may play a part in the maintenance of normal tissue architecture and physiological homeostasis. Images p1345-a
Dobson, H; Pignatelli, M; Hopwood, D; D'Arrigo, C
...Devices Â§ 878.3610 Esophageal prosthesis. (a) Identification. An esophageal prosthesis is a rigid, flexible, or expandable tubular device made of a...esophagus. The metal esophageal prosthesis may be uncovered or...
...Devices Â§ 878.3610 Esophageal prosthesis. (a) Identification. An esophageal prosthesis is a rigid, flexible, or expandable tubular device made of a...esophagus. The metal esophageal prosthesis may be uncovered or...
Communication between the airway epithelium and stroma is evident during embryogenesis, and both epithelial shedding and increased smooth muscle proliferation are features of airway remodeling. Hence, we hypothesized that after injury the airway epithelium could modulate airway smooth muscle proliferation. Fully differentiated primary normal human bronchial epithelial (NHBE) cells at an air-liquid interface were co-cultured with serum-deprived normal primary human airway smooth muscle cells (HASM) using commercially available Transwells. In some co-cultures, the NHBE were repeatedly (x4) scrape-injured. An in vivo model of tracheal injury consisted of gently denuding the tracheal epithelium (x3) of a rabbit over 5 days and then examining the trachea by histology 3 days after the last injury. Our results show that HASM cell number increases 2.5-fold in the presence of NHBE, and 4.3-fold in the presence of injured NHBE compared with HASM alone after 8 days of in vitro co-culture. In addition, IL-6, IL-8, monocyte chemotactic protein (MCP)-1 and, more markedly, matrix metalloproteinase (MMP)-9 concentration increased in co-culture correlating with enhanced HASM growth. Inhibiting MMP-9 release significantly attenuated the NHBE-dependent HASM proliferation in co-culture. In vivo, the injured rabbit trachea demonstrated proliferation in the smooth muscle (trachealis) region and significant MMP-9 staining, which was absent in the uninjured control. The airway epithelium modulates smooth muscle cell proliferation via a mechanism that involves secretion of soluble mediators including potential smooth muscle mitogens such as IL-6, IL-8, and MCP-1, but also through a novel MMP-9-dependent mechanism. PMID:19151317
Malavia, Nikita K; Raub, Christopher B; Mahon, Sari B; Brenner, Matthew; Panettieri, Reynold A; George, Steven C
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.
Fisher, R.S.; Malmud, L.S.; Appelgate, G.; Rock, E.; Lorber, S.H.
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.
Fisher, R.S.; Malmud, L.S.; Applegate, G.; Rock, E.; Lorber, S.H.
We examined 11 pediatric patients with eosinophilic esophagitis with a tardy diagnosis. The symptoms were initially thought to be related to other diseases, leading to the use of inadequate therapeutic approaches. The patients were between 3 and 17 years old (mean 7.8 ± 3.8 years), and 8 of the patients were male. Common symptoms included abdominal pain, regurgitation, difficulty in gaining weight, vomiting, dysphagia, and coughing. The mean age for the onset of symptoms was 4.3 ± 2.9 years. Endoscopic findings included normal mucosa in five (45%) patients, thickening of the mucosa with longitudinal grooves in three (27%), erosive esophagitis in two (18%), and a whitish stippling in one (9%) patient. Treatment included the use of a topical corticosteroid for 10 patients. In eight (73%) cases, the treatment made the symptoms disappear. Ten patients underwent histopathological management after treatment, with a decrease in the number of eosinophils.
Pinheiro, Mayra Isabel Correia; de Goes Cavalcanti, Luciano Pamplona; Honorio, Rodrigo Schuler; de Alencar Moreno, Luis Helder; Fortes, Mayara Carvalho; da Silva, Carlos Antonio Bruno
We examined 11 pediatric patients with eosinophilic esophagitis with a tardy diagnosis. The symptoms were initially thought to be related to other diseases, leading to the use of inadequate therapeutic approaches. The patients were between 3 and 17 years old (mean 7.8 ± 3.8 years), and 8 of the patients were male. Common symptoms included abdominal pain, regurgitation, difficulty in gaining weight, vomiting, dysphagia, and coughing. The mean age for the onset of symptoms was 4.3 ± 2.9 years. Endoscopic findings included normal mucosa in five (45%) patients, thickening of the mucosa with longitudinal grooves in three (27%), erosive esophagitis in two (18%), and a whitish stippling in one (9%) patient. Treatment included the use of a topical corticosteroid for 10 patients. In eight (73%) cases, the treatment made the symptoms disappear. Ten patients underwent histopathological management after treatment, with a decrease in the number of eosinophils. PMID:24106430
Pinheiro, Mayra Isabel Correia; de Góes Cavalcanti, Luciano Pamplona; Honório, Rodrigo Schuler; de Alencar Moreno, Luís Hélder; Fortes, Mayara Carvalho; da Silva, Carlos Antônio Bruno
Background Asthmatics are known to have esophageal hypomotility. Vagal hypofunction and prolonged intra-esophageal acidification cause esophageal hypomotility. The contribution of gastroesophageal reflux (GER) and vagal function to esophageal motility in asthmatics is unclear. We studied the relationship between esophageal motility, GER and vagal function in a cohort of adult asthmatics. Methods Thirty mild, stable asthmatics (ATS criteria) and 30 healthy volunteers underwent 24-hour ambulatory esophageal monitoring, manometry, autonomic function testing and GER symptom assessment. 27 asthmatics underwent gastroscopy. A vagal function score calculated from 3 tests (valsalva maneuver, heart rate response to deep breathing and to standing from supine position) was correlated with esophageal function parameters. Results Asthmatics (mean age 34.8 (SD 8.4), 60% female) had more frequent GERD symptoms than controls (mean age 30.9 (SD 7.7), 50% female). 10/27 asthmatics had esophageal mucosal damage, 22 showed hypervagal response, none had a hyperadrenergic response. 14 asthmatics had ineffective esophageal motility. Higher GERD-score asthmatics had significantly fewer peristaltic and more simultaneous contractions than controls, and higher esophageal acid contact times than those with lower scores. All reflux parameters were significantly higher and acid clearance time prolonged in asthmatics than controls (p?0.001, Mann–Whitney U test). There was no correlation between vagal function score and esophageal function parameters. Conclusions A cohort of adult asthmatics was found to have peristaltic dysfunction and pathological GER, but otherwise normal esophageal motility. The peristaltic dysfunction seems to be associated with vagal hyperreactivity rather than vagal hypofunction.
Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.
Cicala, Michele; Emerenziani, Sara; Guarino, Michele Pier Luca; Ribolsi, Mentore
To study the role of thymic medullary epithelium in tolerance induction, the third and fourth branchial clefts of embryos from E mu-Kb transgenic mice, which express the major histocompatibility complex class I antigen H-2Kb exclusively on medullary thymic epithelium, were grafted to athymic nude mice. The grafts differentiated into tissue that morphologically resembled normal thymus. These grafts expressed the H-2Kb antigen appropriately and gave rise to a functional T cell repertoire. In vivo tolerance to H-2Kb disparate skin grafts was invariably found in mice expressing H-2Kb in the medulla or in both medulla and cortex of C57BL/6 branchial cleft-grafted controls. In marked contrast, in vitro cytotoxicity assays demonstrated reactivity toward H-2Kb in the presence of interleukin 2, and limiting-dilution analyses showed similar frequencies of cytolytic T cell precursors reactive to H-2Kb and to third-party stimulators. Medullary epithelium can, therefore, induce split tolerance, in which in vivo tolerance is accompanied by strong in vitro responses in the presence of interleukin 2. Images
Hoffmann, M W; Allison, J; Miller, J F
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.
Lane, Pierre M.; Lam, Stephen; McWilliams, Annette; Leriche, Jean C.; Anderson, Marshall W.; Macaulay, Calum E.
Esophageal pain manifests as symptoms of heartburn, chest pain, or both. It shares features with other types of visceral pain\\u000a in that it is poorly characterized and not well localized, owing to the divergence of visceral afferents. The esophagus is\\u000a innervated by vagal and visceral spinal afferents, both of which are activated by noxious stimuli and convey information to\\u000a specific
Robert Lee; Ravinder K. Mittal
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. PMID:23677964
Cavellani, Camila Lourencini; Gomes, Nayara Cândida; Silva, Ana Teresa de Melo E; Silva, Renata Beatriz; Ferraz, Mara Lúcia Fonseca; Faria, Humberto Aparecido; Corrêa, Rosana Rosa Miranda; Teixeira, Vicente de Paula Antunes; Rocha, Laura Penna
Herpes simplex virus is a common cause of ulcerative esophagitis in the immunocompromised or debilitated host. Despite a high prevalence of primary and recurrent Herpes simplex virus infection in the general population, Herpes simplex virus esophagitis (HSVE) appears to be rare in the immunocompetent host. We report three cases of endoscopically-diagnosed HSVE in apparently immunocompetent children; the presentation was characterized by acute onset of fever, odynophagia, and dysphagia. In two cases, the diagnosis was confirmed histologically by identification of herpes viral inclusions and culture of the virus in the presence of inflammation. The third case was considered to have probable HSVE based on the presence of typical cold sore on his lip, typical endoscopic finding, histopathological evidence of inflammation in esophageal biopsies and positive serologic evidence of acute Herpes simplex virus infection. Two cases received an intravenous course of acyclovir and one had self-limited recovery. All three cases had normal immunological workup and excellent health on long-term follow-up. PMID:21912064
Al-Hussaini, Abdulrahman A; Fagih, Mosa A
We report four cases of esophageal injury associated with the ingestion of commonly prescribed tablets or capsules. History and clinical characteristics of these cases suggest that the medications failed to transit the esophagus and acted locally to produce esophagitis. A search of English- and foreign-language medical journals documented 221 similar cases due to 26 different types of medication. While most
James Walter Kikendall; Arnold C. Friedman; Morakinyo Anthony Oyewole; David Fleischer; Lawrence F. Johnson
Esophageal scintigraphy with labeled liquid and solid food (water solution of radioactive colloid and mixture of egg with radioactive colloid coagulated by heating) was performed in 34 patients without a history of esophageal diseases permitting qualitative and quantitative characterization of normal motor evacuatory function of the esophagus and the lower esophageal sphincter (LES). Altogether 46 patients with esophageal cancer and stomach cancer with esophageal involvement were investigated before therapy. In cancer of the esophagus its function failed with relation to a tumor site and was in direct proportion to a stage of tumor spreading. The method permitted the determination of the level of a pathological focus, a degree of esophageal permeability, quantification of a degree of esophageal dysfunction, the improvement of functional diagnosis of the esophagus and LES, and the determination of motor disorders at the earliest stages of tumor development. PMID:3262190
Shishkina, V V; Piperkova, E N; Okulov, L V
...Esophageal stethoscope with electrical conductors. 868.1920 Section...Esophageal stethoscope with electrical conductors. (a) Identification...esophageal stethoscope with electrical conductors is a device that...
...Esophageal stethoscope with electrical conductors. 868.1920 Section 868...Esophageal stethoscope with electrical conductors. (a) Identification. An esophageal stethoscope with electrical conductors is a device that is...
Esophageal leiomyosarcoma accounts for only 0.5% of all esophageal tumors. This rare tumor has been reported in middle-aged or elderly patients. In contrast, pediatric esophageal leiomyosarcomas have never been reported. The case described herein is the first report of an esophageal leiomyosarcoma in a pediatric patient with its own characteristics. The patient had symptoms of mild cough without dysphagia. The
Wen-xian Wang; Desai Gaurav; Li Wen; Ming-fu Ye; Qing-rong Sun; Wei-jin Liu; Dong Zhang
Telomeres are repetitive DNA sequences located at the ends of chromosomes. Telomeres are shortened by repeated cell divisions and by oxidative DNA damage, and cells with critically shortened telomeres cannot divide. We hypothesized that chronic gastroesophageal reflux disease (GERD)-induced injury of the esophageal squamous epithelium results in progressive telomeric shortening that eventually might interfere with mucosal healing. To address our hypothesis, we compared telomere length and telomerase activity in biopsy specimens of esophageal squamous epithelium from GERD patients and control patients. Endoscopic biopsies were taken from the esophageal squamous epithelium of 38 patients with GERD [10 long-segment Barrett's esophagus (LSBE), 15 short-segment (SSBE), 13 GERD without Barrett's esophagus] and 16 control patients without GERD. Telomere length was assessed using the terminal restriction fragment assay, and telomerase activity was studied by the PCR-based telomeric repeat amplification protocol assay. Patients with GERD had significantly shorter telomeres in the distal esophagus than controls [8.3 +/- 0.5 vs. 10.9 +/- 1.5 (SE) Kbp, P = 0.043]. Among the patients with GERD, telomere length in the distal esophagus did not differ significantly in those with and without Barrett's esophagus (LSBE 7.9 +/- 0.8, SSBE 8.6 +/- 0.9, GERD without BE 8.7 +/- 1.0 Kbp). No significant differences in telomerase activity in the distal esophagus were noted between patients with GERD and controls (4.0 +/- 0.39 vs. 5.2 +/- 0.53 RIUs). Telomeres in the squamous epithelium of the distal esophagus of patients who have GERD, with and without Barrett's esophagus, are significantly shorter than those of patients without GERD despite similar levels of telomerase activity. PMID:17395902
Souza, Rhonda F; Lunsford, Tisha; Ramirez, Ruben D; Zhang, Xi; Lee, Edward L; Shen, Yuenan; Owen, Charles; Shay, Jerry W; Morales, Carmela; Spechler, Stuart Jon
Gene expression profiles of primary HPV16- and HPV18-infected early stage cervical cancers and normal cervical epithelium: identification of novel candidate molecular markers for cervical cancer diagnosis and therapy
With the goal of identifying genes with a differential pattern of expression between invasive cervical carcinomas (CVX) and normal cervical keratinocytes (NCK), we used oligonucleotide microarrays to interrogate the expression of 14,500 known genes in 11 primary HPV16 and HPV18-infected stage IB–IIA cervical cancers and four primary normal cervical keratinocyte cultures. Hierarchical cluster analysis of gene expression data identified 240
Alessandro D. Santin; Fenghuang Zhan; Eliana Bignotti; Eric R. Siegel; Stefania Cané; Stefania Bellone; Michela Palmieri; Simone Anfossi; Maria Thomas; Alexander Burnett; Helen H. Kay; Juan J. Roman; Timothy J. O'Brien; Erming Tian; Martin J. Cannon; John Shaughnessy; Sergio Pecorelli
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. PMID:18080228
von Arnim, U; Mönkemüller, K; Malfertheiner, P; Straumann, A
Post-traumatic epilepsy (PTE) can create diagnostic confusion when typical epileptic seizures are not manifest. Abdominal symptoms as a manifestation of PTE are rare in this setting. We present a 43-year-old female with paroxysmal chest and abdominal pain, nausea, salivation, and intermittent dysphagia. Esophageal testing demonstrated diffuse esophageal spasm, but smooth muscle relaxants provided no relief. Finally, after history revealed that a motor vehicle accident temporally preceded symptom onset, video electroencephalography confirmed PTE. Therapy with anti-epileptic drug completely resolved symptoms, and the esophageal motor pattern normalized. We speculate that abnormal epileptiform discharges from the seizure focus altered cerebral input to intrinsic esophageal innervation, resulting in inhibitory dysfunction and a picture resembling diffuse esophageal spasm. This is the first report of symptomatic esophageal spasm as a major ictal manifestation of PTE. PMID:23121455
He, Y-Q; Sheng, J-Q; Wang, J-H; An, H-J; Wang, X; Li, A-Q; Wang, X-W; Gyawali, C P
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.
Russell, C.O.; Hill, L.D.; Holmes, E.R. III; Hull, D.A.; Gannon, R.; Pope, C.E. II
Background & Aims Achalasia esophagus is characterized by loss of peristalsis and incomplete esophago-gastric junction (EGJ) relaxation. We studied mechanisms of esophageal emptying in patients with achalasia using simultaneous high-resolution manometery (HRM), multiple intra-luminal impedance (MII), and high frequency intra-luminal ultrasound (HFIUS) image recordings. Methods Achalasia was categorized into 3 subtypes, based on the esophageal response to swallows: types 1 and 2 were defined by simultaneous pressure waves of < 30 mmHg and > 30 mmHg, respectively, and type 3 was defined by spastic simultaneous esophageal contractions. Results Based on HRM, a predominant achalasia pattern of type 2 was characterized by a unique motor pattern that consisted of upper esophageal sphincter contraction, simultaneous esophageal pressure (panesophageal pressurization), and EGJ contraction, following swallows. HFIUS identified longitudinal muscle contraction of the distal esophagus as the cause of panesophageal pressurization in type 2 achalasia. MII revealed that esophageal emptying occurred intermittently (36% swallows) during periods of panesophageal pressurization. Patients with achalasia of types 1 and 3 had no emptying or relatively normal emptying during most swallows, respectively. Conclusion In achalasia, esophageal emptying results from swallow-induced longitudinal muscle contraction of the distal esophagus; which increases esophageal pressure and allows flow across the non relaxed EGJ to take place
Hong, Su Jin; Bhargava, Valmik; Jiang, Yanfen; DenBoer, Debbie; Mittal, Ravinder K.
Background/Aims Rikkunshito (TJ-43), an herbal medicine, has been demonstrated to relieve gastroesophageal reflux symptoms. However, the effects of TJ-43 on esophageal motor functions have not been fully determined. This double-blind crossover study was performed to investigate the effects of TJ-43 on esophageal motor functions and gastroesophageal reflux. Methods The subjects were 10 normal male volunteers. Lower esophageal sphincter pressure and esophageal body peristaltic contractions with and without 1-week administration of TJ-43 were examined in a crossover fashion. Post-prandial gastroesophageal reflux was also determined using a multi-channel impedance pH dual monitor. Results TJ-43 at a standard dose of 7.5 g/day did not significantly augment esophageal peristaltic contraction pressure measured in the proximal, middle and distal segments of the esophagus, whereas increment of resting lower esophageal sphincter pressure was observed in a supine position. In addition, TJ-43 administration did not decrease post-prandial gastroesophageal acid, non-acid reflux events or accelerate esophageal clearance time. Conclusions TJ-43 at a standard dose did not have a significant effect on esophageal motor activity or gastroesophageal reflux in healthy adults.
Morita, Terumi; Adachi, Kyoichi; Ohara, Shunji; Tanimura, Takashi; Koshino, Kenji; Uemura, Tomochika; Naora, Kohji; Kinoshita, Yoshikazu
Esophageal atresia (EA) is a rare congenital malformation consisting of a lack of continuity between the upper and lower esophageal pouches, frequently associated with tracheoesophageal fistula. The prevalence of such rare abnormalities is established by global birth surveillance programs over the world. EUROCAT is a European program covering 1.7 million births since its creation. The prevalence of EA in Europe seems stable over decades. The National Birth Defects Prevention Network in the USA also shows a stable prevalence with a wide range between states or regions. In France, with the implementation of the national rare diseases plan, a reference center for congenital abnormalities of the esophagus was created in 2006 and a national registry for EA began patient inclusion in 2008. This has resulted in the establishment of the national live birth prevalence for EA, prenatal diagnosis rates, and clinical characteristics of EA patients, early survival, and early morbidity. Prevalence rates seem stable all over the world since many decades. Continuous surveillance of congenital abnormalities and specific registries are useful for epidemiologic data but also for public health authorities for helping families of rare diseases patients. PMID:23679022
Sfeir, R; Michaud, L; Salleron, J; Gottrand, F
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)
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.
Taillefer, R.; Beauchamp, G.; Duranceau, A.C.; Lafontaine, E.
Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with a poor prognosis. Cancer-associated fibroblasts (CAFs) affect tumorigenesis by creating an environment primed for growth and invasion through the secretion of factors, including hepatocyte growth factor (HGF) and transforming growth factor ?1 (TGF?1). In the present study, the levels of ?-smooth muscle actin (?-SMA), TGF?1 and HGF were determined immunohistochemically in oesophageal precancerous lesions (low- and high-grade intraepithelial neoplasia; LGIEN and HGIEN, respectively), carcinoma in situ (CIS) and squamous cell carcinoma (SCC). Immunoreactivity was observed in the cytoplasm of oesophageal epithelial cells and stromal fibroblasts. Expression levels of ?-SMA, TGF?1 and HGF increased significantly in the following order: normal, LGIEN, HGIEN, CIS and SCC. In addition, linear correlations between the expression of ?-SMA, TGF?1 and HGF and different lesions were observed. Microvessel density (MVD) was measured in all specimens and increased gradually in the normal, LGIEN, HGIEN, CIS and SCC specimens, successively. A linear correlation between MVD and pathological grade was also observed and the MVD in ?-SMA-, HGF- and TGF?1-positive groups was higher when compared with that of their negative counterparts. The results of the present study indicated that the frequent overexpression of TGF?1 and HGF proteins, secreted by oesophageal epithelium and stromal fibroblasts, promoted the progression of oesophageal precancerous lesions via the proliferation of epithelial cells and angiogenesis, through the upregulation of vascular endothelial growth factor (VEGF) expression.
XU, ZHIBIN; WANG, SHIJIE; WU, MINGLI; ZENG, WEIWEI; WANG, XIAOLING; DONG, ZHIMING
The airway epithelium is the first line of contact with the inhaled external environment and is continuously exposed to and injured by pollutants, allergens, and viruses. However, little is known about epithelial repair and in particular the identity and role of tissue resident stem/progenitor cells that may contribute to epithelial regeneration. The aims of the present study were to identify, isolate, and characterize side population (SP) cells in human tracheobronchial epithelium. Epithelial cells were obtained from seven nontransplantable healthy lungs and four asthmatic lungs by pronase digestion. SP cells were identified by verapamil-sensitive efflux of the DNA-binding dye Hoechst 33342. Using flow cytometry, CD45? SP, CD45+ SP, and non-SP cells were isolated and sorted. CD45? SP cells made up 0.12% ± 0.01% of the total epithelial cell population in normal airway but 4.1% ± 0.06% of the epithelium in asthmatic airways. All CD45? SP cells showed positive staining for epithelial-specific markers cytokeratin-5, E-cadherin, ZO-1, and p63. CD45? SP cells exhibited stable telomere length and increased colony-forming and proliferative potential, undergoing population expansion for at least 16 consecutive passages. In contrast with non-SP cells, fewer than 100 CD45? SP cells were able to generate a multilayered and differentiated epithelium in air-liquid interface culture. SP cells are present in human tracheobronchial epithelium, exhibit both short- and longterm proliferative potential, and are capable of generation of differentiated epithelium in vitro. The number of SP cells is significantly greater in asthmatic airways, providing evidence of dysregulated resident SP cells in the asthmatic epithelium.
Hackett, Tillie-Louise; Shaheen, Furquan; Johnson, Andrew; Wadsworth, Samuel; Pechkovsky, Dmitri V.; Jacoby, David B.; Kicic, Anthony; Stick, Stephen M.; Knight, Darryl A.
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.
Cadranel, S.; Di Lorenzo, C.; Rodesch, P.; Piepsz, A.; Ham, H.R. (Children University Hospital, Brussels (Belgium))
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.
Kamangar, Farin; Chow, Wong-Ho; Abnet, Christian; Dawsey, Sanford
The main objective of the present work is to study the influence of heat treatment on the esophageal cancer detection using the diffuse reflectance (DR) spectral intensity ratio R540/R575 of oxygenated hemoglobin (HbO2) absorption bands to distinguish the epithelial tissues of normal human esophagus and moderately differentiated esophageal squamous cell carcinoma (ESCC) at different heat treatment temperature of 20, 37, 42, 50, and 60°C, respectively. The DR spectra for the epithelial tissues of the normal esophagus and ESCC in vitro at different heat-treatment temperature in the wavelength range 400-650 nm were measured with a commercial optical fiber spectrometer. The results indicate that the average DR spectral intensity overall enhancement with concomitant increase of heat-treatment temperature for the epithelial tissues of normal esophagus and ESCC, but the average DR spectral intensity for the normal esophageal epithelial tissues is relatively higher than that for ESCC epithelial tissues at the same heat-treatment temperature. The mean R540/R575 ratios of ESCC epithelial tissues were always lower than that of normal esophageal epithelial tissues at the same temperature, and the mean R540/R575 ratios of the epithelial tissues of the normal esophagus and ESCC were decreasing with the increase of different heat-treatment temperatures. The differences in the mean R540/R575 ratios between the epithelial tissues of normal esophagus and ESCC were 13.33, 13.59, 11.76, and 11.11% at different heat-treatment temperature of 20, 37, 42, and 50°C, respectively. These results also indicate that the DR intensity ratio R540/R575 of the hemoglobin bands is a useful tool for discrimination between the epithelial tissues of normal esophagus and ESCC in the temperature range from room temperature to 50°C, but it was non-effective at 60°C or over 60°C.
Zhao, Q. L.; Guo, Z. Y.; Si, J. L.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Guo, X.; Zhong, H. Q.; Li, L. Q.; Li, X. Y.
Primary esophageal schwannomas are uncommon. We describe a case of a large asymptomatic primary esophageal schwannoma in a 65-year-old patient. Computed tomography and positron emission tomography revealed an (18)F-fluorodeoxyglucose-avid 11-cm mass arising from the esophagus. A preoperative diagnosis was made via endoscopic ultrasound. The patient underwent a three-field esophagogastrectomy with cervical esophagogastric anastomosis. He remains well and free of recurrence 10 months after treatment. PMID:22450109
Kassis, Edmund S; Bansal, Shelly; Perrino, Carmen; Walker, Jon P; Hitchcock, Charles; Ross, Patrick; Daniel, Vincent C
We report a rare case of a patient with esophageal carcinoma diagnosed using transthoracic echocardiography. This examination proved to be useful in the identification of a paracardiac mediastinal mass. Images of the esophageal carcinoma, of the stent in the esophagus, and the bubbles inside the stent generated with the ingestion of a carbonated beverage, have not been previously published. Therefore, we believe our findings may be useful to other echocardiographers. PMID:23834459
Cianciulli, Tomás F; Saccheri, María C; Lax, Jorge A; Bianchi, Ricardo A; Beck, Martín A; Ferreiro, Daniel E
The esophageal primary motor disorders like achalasia, diffuse esophageal spasm or the nutcracker can involve the upper esophageal sphincter, the esophageal body, the lower esophageal sphincter or a combination of them. This article will focus on the esophageal body and abnormal peristalsis. A normal esophageal peristaltic contraction occurs after a latency period following a swallow and requires a minimum amplitude to be propulsive. Abnormal latencies may generate simultaneous contractions whereas low amplitude contractions may be inefficient i.e. GERD and high amplitude contractions my provoke chest pain or dysfagia i.e. diffuse spasm. The latency period between deglutition and contraction is due to a muscle inhibition immediately after the swallow. This inhibition is due to release of NO by an inhibitory neurone located in the myenteric plexus. At the end of the inhibition, the contraction occurs due to release of acetyl choline by an excitatory cholinergic neurone. The exact interplay between these two neurones will determine the
Stroke is a frequent cause of oropharyngeal dysphagia but may also cause alterations in esophageal motility. The aim of this investigation was to evaluate the effect of bolus taste on the esophageal transit of patients with stroke and controls. Esophageal transit and clearance were evaluated by scintigraphy in 36 patients in the chronic phase of stroke (44-82 years, mean: 63 years) and in 30 controls (33-85 years, mean: 59 years). The patients had a stroke 1-84 months (median: 5.5 months) before the evaluation of esophageal transit. Eight had dysphagia. Each subject swallowed in random order and in the sitting position 5 mL of liquid boluses with bitter (pH=6.0), sour (pH=3.0), sweet (pH=6.9), and neutral (pH=6.8) taste. Transit and clearance duration and the amount of residues were measured in the proximal, middle, and distal esophageal body. There was no difference between patients and controls in esophageal transit or clearance duration. In the distal esophagus, the transit and clearance durations were longer with the sour bolus than with the other boluses in both patients and controls. The amount of residues in the esophageal body was greater in patients than in controls after swallows of the neutral bolus. In control subjects, after swallows of a sour bolus, there was an increase in the amount of residues in the middle and distal esophagus compared with the other boluses. In conclusion, a sour bolus with low pH causes a longer transit and clearance duration in the distal esophageal body. There was no effect of bolus taste or pH on the esophageal transit of patients in the chronic phase of stroke compared with normal volunteers. The longer transit and clearance duration in the distal esophageal body with the sour bolus appears to be a consequence of the low pH of the bolus. PMID:22642501
Alves, L M T; Fabio, S R C; Dantas, R O
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.
Chai, Jianyuan; Jamal, M Mazen
Background: We observed an endoscopic abnormality in a group of children with histological esophagitis. We termed this finding “vertical lines in esophageal mucosa” (VLEM). We examined the relationship between the presence of VLEM and significant histologic changes in esophageal mucosal biopsies. Methods: Between January 1, 1992, and August 31, 1994, the senior author (JFF) performed 255 esophageal biopsies. The procedure
Sandeep K. Gupta; Joseph F. Fitzgerald; Sonny K. F. Chong; Joseph M. Croffie; Margaret H. Collins
Overexpression of FGF-2 is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer,\\u000a and these risks are reduced in tumors co-expressing the FGF antisense (FGF-AS) RNA. The aim of this study was to characterize\\u000a the expression of alternatively spliced FGF-AS transcripts and encoded nudix-motif proteins in normal human tissues and in\\u000a esophageal adenocarcinoma, and to correlate
Shuo Cheng Zhang; Christie Barclay; Leigh Ann Alexander; Laurette Geldenhuys; Geoffrey A. Porter; Alan G. Casson; Paul R. Murphy
Background The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research. Methods In the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n?=?89) and normal esophageal mucosae (n?=?26) using a 1H nuclear magnetic resonance (1H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant anlaysis (OPLS-DA) were applied to analyse 1H-NMR profiling data to identify potential biomarkers. Results The constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II?=?28; stage III?=?45 and stage IV?=?16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of esophageal cancer tissues, indicating the attribution of metabolites disturbance to the progression of esophageal cancer. The potential biomarkers provide a promising molecular diagnostic approach for clinical diagnosis of human esophageal cancer and a new direction for the mechanism study.
Measurement of radionuclide esophageal transit (RT) using a liquid bolus has been suggested as a screening test for esophageal motor disorders (EMD). The authors prospectively evaluated RT in 49 patients referred for esophageal manometry. Ten subjects with normal manometry served as controls. RT was performed using two 10 ml boluses of water labeled with 250 ..mu..Ci /sup 99m/Tc-sulfur colloid. Patients were studied supine and the swallow sequences framed in 1 second intervals. Transit time was measured from the time of entry to the time of exit from the esophagus. Mean transit time in normal subjects was 9.1 +- 2.1 (SD) sec. The test was abnormal if the transit time was prolonged (> 15 sec) in at least 1 of 2 swallows. RT agreed with manometry in 36/49 patients (75%), including 9/9 achalasics, 3/3 diffuse esophageal spasm, 3/7 'nutcracker esophagus' and 7/8 non-specific motor disorders (NSMD). 4/18 patients with normal manometry had abnormal RT. 9/31 patients with abnormal manometry had normal RT, including 4/7 nutcracker esophagus, 3/3 hypertrensive LES, 1/1 scleroderma and 1/8 NSMD. Sensitivity of RT was 70% and specificity 77%. The false positive rate was 15% and the false negative rate 39%. The authors conclude the following: 1) RT identifies patients with absent or impaired peristalsis; 2) There is substantial incidence of false negatives among patients with manometric disorders but normal peristalsis; and 3) Abnormal RT did occur in some patients with normal menometry. RT using a liquid bolus may not be sensitive enough as a screening test for EMD, but it may be an important adjunct to manometry.
Holloway, R.H.; Lange, R.C.; Magyar, L.; Greene, R.; McCallum, R.W.
pS2-TFF 1 is expressed in breast cancers and has been investigated as a potential prognostic factor reflecting oestrogen dependence. The relationship to the expression of other trefoil peptides, human spasmolytic polypeptide (hSP-TFF 2) and intestinal trefoil factor (hITF/hPI.B-TFF 3) is documented here. Fifty-seven breast specimens were selected from surgical pathology archives and included five normal breasts (two lactating), seven benign proliferative lesions, 11 ductal carcinomas in situ (DCIS), three lobular carcinomas in situ (LCIS), 24 invasive ductal carcinomas (IDC), and seven invasive lobular carcinomas (ILC). The comparative distribution of trefoil mRNAs was assessed by in situ hybridization using 35S-labelled riboprobes and immunohistochemical staining for pS2-TFF 1 and hSP-TFF 2. pS2-TFF 1 and hITF/hPI.B-TFF 3 mRNA were focally present at low signal intensity in normal and benign breast. Both pS2-TFF 1 and hITF/hPI.B-TFF 3 were expressed in all DCIS, LCIS and ILC, and 21/24 IDC. Overall, expression patterns of pS2-TFF 1 and hITF/hPI.B-TFF 3 coincided, but hITF/hPI.B-TFF 3 mRNA was usually found in a greater proportion of cells. Expression of hSP-TFF 2 peptide or mRNA was not detected in any of these cases. MCF 7 breast carcinoma cells also expressed hITF/hPI.B-TFF 3 and pS2-TFF 1 mRNAs but not hSP-TFF 2. hITF/hPI.B-TFF 3 co-expression with pS2-TFF 1 may act as a prognostic factor, but also raises questions about the regulatory pathway for pS2-TFF 1 hITF/hPI.B-TFF 3. Trefoil factors have effects on cell motility and spreading in vitro, and co-expression of hITF/hPI.B-TFF 3 with pS2-TFF 1 could be functionally significant if they form a heterodimer or compete for receptor binding. Absence of hSP-TFF 2 expression may be of equal relevance to tumour cell biology. PMID:9370944
Poulsom, R; Hanby, A M; Lalani, E N; Hauser, F; Hoffmann, W; Stamp, G W
...Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Diagnostic Devices Â§ 868.1910 Esophageal stethoscope. (a) Identification. An esophageal...
...Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices Â§ 868.5650 Esophageal obturator. (a) Identification. An esophageal...
We report a case of esophageal web demonstrated with sonography in a 45-year-old woman with dysphagia. The esophageal web was incidentally detected as a circumferential hypoechoic membrane on sonograms of the cervical esophagus. PMID:16547989
Rokade, Muktachand Laxman
...FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices Â§ 876.5365 Esophageal dilator. (a) Identification. An esophageal...
MYH is an important enzyme in combating DNA oxidative stress in the occurrence and development of various types of tumors. To investigate the correlation between expression of the DNA repair enzyme MYH in esophageal squamous cell carcinoma and 8-oxoguanine (8-oxoG) oxidative damage, as well as the clinical significance of altered MYH expression, tissues from 175 esophageal carcinoma cases were investigated in the present study. MYH expression and 8-oxoG oxidative damage in squamous cell carcinoma and adjacent normal tissue were assessed by immunohistochemistry and Western blotting. In 82.9% (145/175) of the cases, MYH protein expression in esophageal squamous cell carcinoma was lower than that of adjacent normal tissue (t=4.24, P<0.001). Additionally, 8-oxoG staining was higher in the tumors than in the normal tissue. Lower expression of MYH in esophageal squamous cell carcinoma was associated with depth of invasion, venous invasion, TNM stage and lymph node metastasis (P<0.05). In conclusion, a lower MYH expression level in esophageal cell carcinoma tissue was inversely associated with more severe 8-oxoG oxidative damage, suggesting that changes in MYH activity correspond to increased DNA damage in tumor cells. The use of MYH expression as a postoperative index for esophageal squamous cell carcinoma may guide the formulation of individualized chemotherapy for patients after surgery. PMID:22977630
Shen, Kai; Ji, Yong; Chen, Guo-Qiang; Huang, Bin; Zhang, Xian; Wu, Song; Yu, Gui-Ping; Wang, Xiao-Chen
\\u000a Esophageal cancer is the fifth most common gastrointestinal cancer and the ninth leading cause of cancer death in the United\\u000a States. The incidence of esophageal adenocarcinoma is on the rise. Accurate staging of esophageal cancer is critical for the\\u000a selection of appropriate treatment. Endoscopic ultrasound (EUS) plays an important role in the staging of esophageal cancer.\\u000a EUS provides a detailed
Audrey H. Calderwood; Brian C. Jacobson
The long-term effects of gastric banding on esophageal function are not well described. This report describes a 28-year-old woman who developed signs and symptoms of abnormal esophageal motility and lower esophageal sphincter hypotension after gastric banding for morbid obesity. The current literature addressing the effects of gastric banding on esophageal function in light of this case report is discussed. PMID:17509126
O'Rourke, R W; Deveney, C W; McConnell, D B; Wolfe, B M; Jobe, B A
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.
Hong, Jinwha; Lam-Tsai, Yvette; Gress, Frank
The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver–operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (P<0.001). NELL1
Z Jin; Y Mori; J Yang; F Sato; T Ito; Y Cheng; B Paun; J P Hamilton; T Kan; A Olaru; S David; R Agarwal; J M Abraham; D Beer; E Montgomery; S J Meltzer
Summary Initially found expressed in neuronal and then later in endothelial cells, it is well established that the transmembrane glycoproteins neuropilin-1 (NRP1) and neuropilin-2 (NRP2) play essential roles in axonal growth and guidance and in physiological and pathological angiogenesis. Neuropilin expression and function in epithelial cells has received little attention when compared with neuronal and endothelial cells. Overexpression of NRPs is shown to enhance growth, correlate with invasion and is associated with poor prognosis in various tumour types, especially those of epithelial origin. The contribution of NRP and its ligands to tumour growth and metastasis has spurred a strong interest in NRPs as novel chemotherapy drug targets. Given NRP’s role as a multifunctional co-receptor with an ability to bind with disparate ligand families, this has sparked new areas of research implicating NRPs in diverse biological functions. Here, we review the growing body of research demonstrating NRP expression and role in the normal and neoplastic epithelium.
Wild, Jonathan R L; Staton, Carolyn A; Chapple, Keith; Corfe, Bernard M
The A-kinase anchoring protein 12 (AKAP12) is a kinase scaffold protein with known tumor suppressor activity. Recently, AKAP12 promoter hypermethylation was reported in gastric and colorectal cancers. We examined AKAP12 promoter hypermethylation using real-time methylation-specific PCR in 259 human esophageal tissues. AKAP12 hypermethylation showed highly discriminative receiver-operator characteristic (ROC) curve profiles, clearly distinguishing esophageal adenocarcinoma (EAC) from esophageal squamous cell carcinoma and normal esophagus (P < 0.0001). AKAP12-normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's, and EAC than in normal esophagus (P < 0.0000001). AKAP12 hypermethylation frequency was zero in normal esophagus but increased early during neoplastic progression, to 38.9% in BE from patients with Barrett's alone, 52.5% in dysplastic Barrett's metaplasia, and 52.2% in EAC. AKAP12 hypermethylation levels were significantly higher in normal esophageal epithelia from patients with EAC (mean = 0.00082) than in normal esophagi from patients without Barrett's or esophageal cancer (mean = 0.00007; P = 0.006). There was a significant correlation between AKAP12 hypermethylation and BE segment length, a known clinical neoplastic progression risk factor. In contrast, only 2 (7.7%) of 26 esophageal squamous cell carcinomas exhibited AKAP12 hypermethylation. Treatment of BIC and OE33 EAC cells with 5-aza-2'-deoxycytidine reduced AKAP12 methylation and increased AKAP12 mRNA expression. AKAP12 mRNA levels in EACs with unmethylated AKAP12 (mean = 0.1663) were higher than in EACs with methylated AKAP12 (mean = 0.0668). We conclude that promoter hypermethylation of AKAP12 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker for the early detection of EAC. PMID:18199717
Jin, Zhe; Hamilton, James P; Yang, Jian; Mori, Yuriko; Olaru, Alexandru; Sato, Fumiaki; Ito, Tetsuo; Kan, Takatsugu; Cheng, Yulan; Paun, Bogdan; David, Stefan; Beer, David G; Agarwal, Rachana; Abraham, John M; Meltzer, Stephen J
OBJECTIVE:: Esophageal varices are a consequence of portal hypertension in cirrhotic patients. Current guidelines recommend that all cirrhotic patients undergo screening endoscopy at diagnosis to identify patients with varices at high risk of bleeding who will benefit from primary prophylaxis. This practice increases costs, involves a degree of invasiveness and discomfort and places a heavy burden on endoscopy units. Several studies have evaluated possible noninvasive predictors of esophageal varices, but most of these studies remain controversial. METHODS:: The intra-abdominal portion of the esophagus in 673 patients who presented with liver cirrhosis and portal hypertension was examined using standard 2-dimensional (2D) ultrasound. A direct relationship between the degree of varices observed on upper endoscopy and the intra-abdominal esophageal wall thickness was detected using 2D ultrasound. RESULTS:: The mean thicknesses of the esophageal wall were 3.7 ± 0.5 mm (mean ± standard deviation) in normal individuals, 7.3 ± 3.3 mm in those with esophageal varices and 8.65 ± 1.98 mm in those with risky esophageal varices. The overall accuracy of 2D ultrasound was 95%. CONCLUSIONS:: The intra-abdominal esophagus should be observed during abdominal ultrasound examination in patients with liver cirrhosis. Two-dimensional ultrasound can play an important role in screening for esophageal varices. PMID:23267234
Abd Elrazek, Abd Elrazek Mohammad Ali; Mahfouz, Hamdy; Afifi, Mohamed; Nafady, Mohamed; Fathy, Abd El Wahhab; Elazeem, Khaled Abd; Amer, Khaled; El-Shamy, Ahmed; Kenji, Uryuhara; Ghaibeh, A Ammar; Bilasy, Shymaa; El-Ansary, Nadia; Fakhry, Mohamed; Mansour, Magdy
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.
Monajemzadeh, Maryam; Haghi-Ashtiani, Mohammad-Taghi; Soleymani, Roohallah; Shams, Sedigheh; Taleb, Shayandokht; Motamed, Farzaneh; Najafi, Mehri; Abbasi, Ata
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.
Rundback, J.H.; Goldfarb, C.R.; Ongseng, F. (Beth Israel Medical Center, New York, NY (USA))
Background: Esophageal replacement is associated with significant morbidity that may lead to operative interventions. This study reviews the management and outcome of children who underwent reoperation after esophageal replacement.Methods: Eighteen patients who underwent esophageal replacement from 1985 to 1997 were reviewed retrospectively. Ten patients underwent reoperation. Patient management, perioperative morbidity, and the dietary intake at follow-up were recorded for each
James C. Y Dunn; Eric W Fonkalsrud; Harry Applebaum; William W Shaw; James B Atkinson
An attempt is made to explore those aspects of the history of esophageal surgery relevant to pediatric practice. In some areas, the history is entirely focused on conditions of particular pediatric significance; esophageal atresia is a classic example of this group. In other areas there is considerable overlap, which varies in extent, with the history of esophageal surgery in adult.
N. A. Myers
Extraesophageal manifestations of gastroesophageal reflux may be best diagnosed using ambulatory esophageal pH monitoring. This test involves the placemenmt of a thin pH probe in the esophagus, which is connected to a small box on a waistbelt. Studies are done in an ambulatory state in the patient's home and work environment. Data collected assesses acid exposure time over the circadian cycle and the relationship of symptoms to pH drops. Studies in adult asthmatics demonstrate abnormal amounts of acid reflux by 24-hour esophageal pH monitoring in >50% of patients. Likewise, large studies in patients with chronic ENT complaints find abnormal acid reflux values in 50-80% of patients. Several problems and issues with ambulatory pH monitoring still need addressing, including (1) the need for dual pH monitoring, (2) artifact and reproducibility, (3) normal values, (4) role in the initial diagnosis, and (5) role in the follow-up of poorly responding patients. PMID:9422638
Richter, J E
Polymyositis (PM) and dermatomyositis (DM) may be associated with motor dysfunction of the entire gastrointestinal tract. Abnormal esophageal motor function is a well-recognized complication of these diseases. In this study, we used a solid phase esophageal study to evaluate the motor function in patients with PM or DM. Twenty-three patients and 36 age-matched normal volunteers were studied. Each subject was placed in a supine position above a gamma camera linked to a computer and was given a 4-ml bolus of solid gelatin containing 1 mCi of Tc-99m phytate. Data were acquired in the list mode. A computer method modified from Kelim and Wald and Russell et al. was used to calculate the following: A) total mean transit time (MTT); B) residual fraction after the first swallow (RF); and C) retrograde index (RI). All values are presented as mean +/- standard deviation (SD). The Student's t-test was used to test statistical significance. Our preliminary results suggest: 1) delayed esophageal emptying is common (17/23) in PM/DM, indicating frequent malfunction of the smooth muscle of the upper gastrointestinal tract in PM/DM and 2) measurement of esophageal motility may monitor disease activity in PM/DM. PMID:8340957
Wang, S J; Lin, W Y; Hsu, C Y; Kao, C H; Chang, C P; Lan, J L
Patient: Female, 40 Final Diagnosis: Esophageal lipoma Symptoms: — Medication: — Clinical Procedure: Laparoscopic enucleation Specialty: Surgery Objective: Rare disease Background: Benign tumors of the esophagus are very rare, constituting only 0.5% to 0.8% of all esophageal neoplasms. Approximately 60% of benign esophageal neoplasms are leiomyomas, 20% are cysts, 5% are polyps, and less than 1% are lipomas. Case Report: A 40-year-old woman was referred to our department with dysphagia that had progressively worsened during the previous 2 years. Physical examination on admission produced normal findings. Upper gastrointestinal endoscopy revealed a submucosal space-occupying mass in the posterior wall of the lower esophagus, with normal mucosa. The mass was yellowish and soft. A computed tomography (CT) of the chest revealed a submucosal esophageal lesion in the posterior wall, with luminal narrowing of the distal esophagus. Thus, a submucosal tumor was identified in this region and esophageal submucosal lipoma was considered the most likely diagnosis. A laparoscopic operation was performed. The tumor was completely enucleated, and measured 10×7×2.5 cm. The pathology showed lipoma. The postoperative course was uneventful, and the patient was discharged 4 days after the operation. Conclusions: Benign tumors of the esophagus are very rare. Laparoscopic transhiatal enucleation of lower esophageal lipomas and other benign tumors is a safe and effective operation.
Tsalis, Konstantinos; Antoniou, Nikolaos; Kalfadis, Stavros; Dimoulas, Avraam; Dagdilelis, Alexandros Karolidis Loukas; Lazaridis, Charalampos
Nonmuscle myosin IIA (myosin IIA) is a force-producing protein involved in the process of cell migration. Its expression has been considered as a bad prognostic indicator in stage I lung adenocarcinoma. However, the expression and clinical significance of myosin IIA in esophageal cancer has not been explored. In this study, we investigate the expression level of myosin IIA in 50 esophageal squamous cancer and 30 adjacent normal esophageal tissues by immunohistochemical staining and correlated its expression with clinicopathological features. Myosin IIA was expressed in all esophageal squamous cancer tissues (100%) and 8 of 30 adjacent normal tissues (26.7%, P = 0.000). In cancer tissues, elevated myosin IIA expression level was significantly correlated with increasing metastatic lymph nodes, poorer cancer differentiation, and advanced tumor stage. Further univariate analysis suggested that strong myosin IIA expression was associated with a significantly shorter overall survival (P = 0.021). In addition, MYH9 SiRNA was transfected into esophageal squamous cancer cell line (KYSE-510) to study the role of myosin IIA in cell migration. SiRNA-mediated depletion of myosin IIA in KYSE-510 cells significantly increased cell-matrix adhesion and attenuated cell migration ability (P = 0.000). In conclusion, these findings indicate that overexpression of myosin IIA may contribute to the progression and poor prognosis of esophageal squamous cancer, and this effect may be associated with increased cancer cell migration. PMID:21951916
Xia, Z-K; Yuan, Y-C; Yin, N; Yin, B-L; Tan, Z-P; Hu, Y-R
Estrogen receptors (ERs) are frequently expressed in human tumor tissues. There have been several studies concerning ER expression in esophageal cancers, yet the results are inconsistent, and the prognostic value of the receptors remains unclear. In the present study, we investigated the expression of ER protein and its correlation with clinical features of esophageal squamous cell carcinoma (ESCC) patients. Immunohistochemical staining for the ERs was carried out on paraffin-embedded primary tumor tissue sections from 89 patients with ESCC. Quantitative analyses were performed to determine the prognostic value of the expression of ERs, and Pearson's correlation was used to examine the relationship between ER? and ER? expression levels. Our results showed that ER? immunoreactivity was significantly lower in ESCC than that in the non-neoplastic epithelium (P=0.0445), whereas the ER? status was much stronger in ESCC than that in the non-neoplastic epithelium (P=0.0243). A significant inverse correlation was observed between ER? expression and depth of tumor invasion (P=0.0426). Correlation analysis revealed a statistically significant inverse correlation between the expression of ER? and ER? in ESCC (r=-0.2902, P=0.0058). Kaplan-Meier survival analysis showed that the patients with ER? expression (21/89) had a better outcome than patients without ER? expression (P=0.0280), whereas patients with high ER? immunoreactivity (44/89) were significantly associated with worse survival (P=0.0366). In conclusion, ER? and ER? levels were inversely correlated, and the downregulation of ER? and upregulation of ER? may indicate unfavorable prognosis of ESCC. PMID:24101172
Dong, Jing; Jiang, Shi-Wen; Niu, Yanru; Chen, Ling; Liu, Shuyan; Ma, Tianzhong; Chen, Xiancai; Xu, Liyan; Su, Zhongjing; Chen, Haibin
Rat and human biliary epithelium is morphologically and functionally heterogeneous. Since no information exists on the heterogeneity of the murine intrahepatic biliary epithelium, and with increased usage of transgenic mouse models to study liver disease pathogenesis, we sought to evaluate the morphological, secretory and proliferative phenotypes of small and large bile ducts and purified cholangiocytes in normal and cholestatic mouse models. Methods For morphometry, normal and BDL mouse livers (C57/BL6) were dissected into blocks of 2-4 ?m2, embedded in paraffin, sectioned, and stained with H&E. Sizes of bile ducts and cholangiocytes were evaluated by using SigmaScan to measure the diameters of bile ducts and cholangiocytes. In small and large normal and BDL cholangiocytes, we evaluated the expression of cholangiocyte specific markers, keratin-19 (KRT19), secretin receptor (SR), cystic fibrosis transmembrane conductance regulator (CFTR), and chloride bicarbonate anion exchanger 2 (Cl-/HCO-3 AE2) by immunofluorescence and western blot; and intracellular cAMP levels and chloride efflux in response to secretin (100 nM). To evaluate cholangiocyte proliferative responses after bile duct ligation (BDL), small and large cholangiocytes were isolated from BDL mice. The proliferation status was determined by analysis of the cell cycle by FACS and bile duct mass was determined by the number of KRT19-positive bile ducts in liver sections. Results In situ morphometry established that the biliary epithelium of mice is morphologically heterogeneous, which smaller cholangiocyte lining smaller bile ducts and larger cholangiocytes lining larger ducts. Both small and large cholangiocytes express KRT19 and only large cholangiocytes from normal and BDL mice express SR, CFTR, and Cl-/HCO-3 exchanger and respond to secretin with increased cAMP levels and chloride efflux. Following BDL, only large mouse cholangiocytes proliferate. Conclusion Similar to rats, mouse intrahepatic biliary epithelium is morphologically, and functionally heterogeneous. The mouse is a suitable model for defining the heterogeneity of the biliary tree.
Glaser, Shannon; Gaudio, Eugenio; Rao, Arundhati; Pierce, Lisa; Onori, Paolo; Franchitto, Antonio; Francis, Heather; Dostal, David E; Venter, Julie; DeMorrow, Sharon; Mancinelli, Romina; Carpino, Guido; Alvaro, Domenico; Kopriva, Shelley; Savage, Jennifer; Alpini, Gianfranco
Aim: The effects of the administration of three tear substitutes on normal conjunctival epithelium of the mouse, with particular regard to goblet cells, were studied. Methods: Three-month-old Swiss CD 1 mice were divided into four groups of 7 animals each. Group 1 was untreated (control). The other animals were treated with the instillation of 5 drops\\/day for 10 days as
Pasquale Aragona; Antonio Micali; Grazia Paladino; Felicia Ferreri; Domenico Puzzolo
\\u000a Cystic fibrosis (CF) is a multiorgan lethal inherited disease, affecting about 2000-5000 children and adults of Caucasian\\u000a origin. Most of the major manifestations of the disease are related to a primary defect in the protein product of the cystic\\u000a fibrosis transmembrane conductance regulator (CFTR) gene which is normally present in the apical membrane of the airway surface epithelium and submucosal
Edith Puchelle; Jean-Marie Zahm; Sophie de Bentzmann; Dominique Gaillard
The purpose of this study was to describe the quantitatively and qualitatively genes expressed in in vivo human conjunctival epithelium. A cDNA library was created from human conjunctival epithelial cells obtained from 38 normal eyes by brush cytology. Poly A+RNA isolated from these cells was used as a template for cDNA synthesis by the vector-priming method. A 3?-directed cDNA library
Atsuyoshi Dota; Kohji Nishida; Wakako Adachi; Takahiro Nakamura; Noriko Koizumi; Shoko Kawamoto; Kousaku Okubo; Shigeru Kinoshita
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. In brief, formidable strides have been made in biochemistry specific to this important target tissue, despite the inability to acquire tracheobronchial epithelium in large quantities.
Mass, M J; Kaufman, D G
Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Stage IB Esophageal Cancer; Stage IIA Esophageal Cancer; Stage IIB Esophageal Cancer; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer
Abnormalities of the esophagus are common, and complications associated with these disorders and diseases can involve the mediastinum, tracheobronchial tree, and lungs. The most common complications include mediastinitis secondary to esophageal perforation or postoperative anastomotic leak, or both; empyema due to fistula formation; and aspiration pneumonia. The authors reviewed the radiologic appearances of those and other common thoracic complications associated with esophageal disorders to facilitate early detection, diagnosis, and management. Computed tomographic (CT) findings of acute mediastinitis secondary to esophageal perforation may include esophageal thickening, extraluminal gas, pleural effusion, single or multiple abscesses, and extraluminal contrast medium. The radiologic manifestations of pneumonia secondary to tracheoesophageal fistula are variable, depending on the spread and severity of the aspiration. The most common radiographic pattern is that of bronchopneumonia with scattered air-space opacities. CT has been regarded as the imaging modality of choice for the evaluation of suspected esophagopleural fistula, because the site of communication between the pleural space and the esophagus can often be seen. An awareness of the radiologic manifestations of these complications is thus required to facilitate early diagnosis. PMID:12376614
Giménez, Ana; Franquet, Tomás; Erasmus, Jeremy J; Martínez, Santiago; Estrada, Pilar
Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated. PMID:21438963
Lucendo, A J
The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea.
Cenedella, R.J.; Fleschner, C.R. (Kirksville College of Osteopathic Medicine, MO (USA))
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.
Thompson, W.M.; Halvorsen, R.A.; Foster, W.L. Jr.; Williford, M.E.; Postlethwait, R.W.; Korobkin, M.
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.
Stein, H J; DeMeester, T R; Naspetti, R; Jamieson, J; Perry, R E
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death in China. In the present study, proteins\\u000a in tumors and adjacent normal esophageal tissues from 41 patients with ESCC were extracted, and two-dimensional electrophoresis\\u000a (2-DE) was performed using the pH 3–10 and 4–7 immobilized pH gradient strips. The protein spots expressed differentially\\u000a between tumors and normal tissues
Xiao-Li Du; Hai Hu; De-Chen Lin; Shu-Hua Xia; Xiao-Ming Shen; Yu Zhang; Man-Li Luo; Yan-Bin Feng; Yan Cai; Xin Xu; Ya-Ling Han; Qi-Min Zhan; Ming-Rong Wang
The capability of using silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) spectroscopy combined with principal component analysis (PCA) and linear discriminate analysis (LDA) to differentiate esophageal cancer tissue from normal tissue was presented. Significant differences in Raman intensities of prominent SERS bands were observed between normal and cancer tissues. PCA-LDA multivariate analysis of the measured tissue SERS spectra achieved diagnostic sensitivity of 90.9% and specificity of 97.8%. This exploratory study demonstrated great potential for developing label-free tissue SERS analysis into a clinical tool for esophageal cancer detection.
Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan
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.
Jiang, Yanfen; Bhargava, Valmik; Kim, Young Sun
After repair of esophageal atresia (EA) in a newborn, esophageal dysmotility presenting as dysphagia and symptomatic gastroesophageal reflux are common. Significant esophageal morbidity associated with EA extends into adulthood. In adulthood approximately one-fifth of the patients have developed epithelial metaplastic changes, one-third of these have intestinal metaplasia (Barrett esophagus). Surgical complications, increasing age, and impaired esophageal motility predict the development of epithelial metaplasia after repair of EA. To date, worldwide, eight cases of esophageal cancer have been reported in young adults treated for EA. Incidence of esophageal cancer after EA repair is very much likely to increase in the future. Life-long endoscopic follow-up is warranted in patients with EA. PMID:23737132
Rintala, R J; Pakarinen, M P
Objective To evaluate TGF-?1 expression in polypoid mucosa (epithelium and stroma) of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods Cross-sectional study with two groups: 17 patients with nasal polyposis and 11 controls. Polyps and normal nasal mucosa were processed by immunohistochemical methods for TGF-?1 visualization. Then, the percentage of TGF-?1 expression in stroma and epithelium was objectively quantified using UT Morph software. Results A lower percentage of positive expression was found in the epithelium of CRSwNP patients (32.44%) versus normal controls (55.91%) (p?0.05), and a higher percentage of positive expression in the stroma of CRSwNP patients (23.24%) versus controls (5.88%) (p?0.05). Conclusion The lower percentage of TGF-?1 expression in the nasal epithelium of CRSwNP patients may have an impact on epithelium-directed topical treatments employed in this patient population.
Background: Primary eosinophilic esophagitis, a chronic inflammatory disorder of the esophagus, evokes recurrent dysphagia. Endoscopy is often unremarkable, and no consensus exists regarding management of resultant dysphagia. The response of a series of patients with primary eosinophilic esophagitis to dilation is reported together with a description of a possibly pathognomonic sign: fragile esophageal mucosa, for which the term “crêpe-paper” mucosa
Alex Straumann; Livio Rossi; Hans-Uwe Simon; Pius Heer; Hans-Peter Spichtin; Christoph Beglinger
Benign esophagorespiratory fistula is a rare but often lethal affection and difficult to cure. Possible treatments are surgery or esophageal stenting but may fail and cause respiratory failure. Two patients with spontaneous esophagorespiratory fistula after chemoradiotherapy for an esophageal malignancy were both treated by esophageal exclusion but esophageal stent were left in place. The esophageal stents were transtracheally removed through the fistula. The removals were successful, patients could leave Intensive Care Unit and returned home. Transtracheal esophageal stent removal is technically possible but very risky. Such situations must be avoided: esophageal stents must absolutely be removed before esophageal exclusion.
Buiret, Guillaume; Guiraud, Michel; Pierron, Jerome; Schoeffler, Mathieu; Duperret, Serge; Baulieux, Jacques; Wander, Lionel; Poupart, Marc; Pignat, Jean-Christian
This paper will review the pathologic definition of chronic lymphocytic thyroiditis, its relationships and epidemiology, and its association with thyroid neoplasms. The epithelium of thyroid glands affected by lymphocytic thyroiditis has been studied by various techniques. Immunohistochemical markers, oncogene changes and genetic mutations that are shared by the thyroiditic epithelium and papillary thyroid carcinoma will be reviewed. Morphologic similarities of
Virginia A. LiVolsi
Surgery is an essential part of the treatment of patients with esophageal carcinoma. However, there is no consensus on whether the surgical technique can be improved to promote better survival outcome. Specifically, the real value of the addition of a radical lymphadenectomy to the esophageal resection is still elusive and controversial. This paper focuses on the debate of esophagectomy and lymphadenectomy for the treatment of esophageal cancer. PMID:23553174
Herbella, Fernando A M; Laurino Neto, Rafael M; Allaix, Marco E; Patti, Marco G
\\u000a Esophageal carcinoma is an uncommon gastrointestinal malignancy with a prevalence rate which is far less than the more common\\u000a colo-rectal cancers. Whereas the overall incidence of esophageal cancer has risen only gradually with time, in the United\\u000a States, Canada, and Western Europe, there has been a dramatic change in the distribution of esophageal cancer by cell type\\u000a (figure 1). Currently
f. Richard; m. d. Heitmiller
Clinical studies implicate adenosine acting on esophageal nociceptive pathways in the pathogenesis of noncardiac chest pain originating from the esophagus. However, the effect of adenosine on esophageal afferent nerve subtypes is incompletely understood. We addressed the hypothesis that adenosine selectively activates esophageal nociceptors. Whole cell perforated patch-clamp recordings and single-cell RT-PCR analysis were performed on the primary afferent neurons retrogradely labeled from the esophagus in the guinea pig. Extracellular recordings were made from the isolated innervated esophagus. In patch-clamp studies, adenosine evoked activation (inward current) in a majority of putative nociceptive (capsaicin-sensitive) vagal nodose, vagal jugular, and spinal dorsal root ganglia (DRG) neurons innervating the esophagus. Single-cell RT-PCR analysis indicated that the majority of the putative nociceptive (transient receptor potential V1-positive) neurons innervating the esophagus express the adenosine receptors. The neural crest-derived (spinal DRG and vagal jugular) esophageal nociceptors expressed predominantly the adenosine A1 receptor while the placodes-derived vagal nodose nociceptors expressed the adenosine A1 and/or A2A receptors. Consistent with the studies in the cell bodies, adenosine evoked activation (overt action potential discharge) in esophageal nociceptive nerve terminals. Furthermore, the neural crest-derived jugular nociceptors were activated by the selective A1 receptor agonist CCPA, and the placodes-derived nodose nociceptors were activated by CCPA and/or the selective adenosine A2A receptor CGS-21680. In contrast to esophageal nociceptors, adenosine failed to stimulate the vagal esophageal low-threshold (tension) mechanosensors. We conclude that adenosine selectively activates esophageal nociceptors. Our data indicate that the esophageal neural crest-derived nociceptors can be activated via the adenosine A1 receptor while the placodes-derived esophageal nociceptors can be activated via A1 and/or A2A receptors. Direct activation of esophageal nociceptors via adenosine receptors may contribute to the symptoms in esophageal diseases.
Ru, F.; Surdenikova, L.; Brozmanova, M.
Background. The association of congenital stenosis of the distal esophagus (CES) in children with esophageal atresia\\/tracheoesophageal\\u000a fistula complex (TEF) has been described but is thought to be rare. Most reports have been of individual or small numbers\\u000a of cases. Objective. The objective of the study was to evaluate the incidence, clinical and radiographic features of CES associated with TEF,\\u000a and
Beverley Newman; Thomas M. Bender
Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients, and approximately 5–15% of cirrhosis patients show newly formed varices or worsening of varices each year. The major therapeutic strategy of esophageal varices consists of primary prevention, treatment for bleeding varices, and secondary prevention, which are provided by pharmacological, endoscopic, interventional and surgical treatments. Optimal management of esophageal varices requires a clear understanding of the pathophysiology and natural history. In this paper, we outline the current knowledge and future prospect in the pathophysiology of esophageal varices and portal hypertension.
Maruyama, Hitoshi; Yokosuka, Osamu
AIM: To investigate the association between human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in southern Brazil. METHODS: We studied 189 esophageal samples from 125 patients from three different groups: (1) 102 biopsies from 51 patients with ESCC, with one sample from the tumor and another from normal esophageal mucosa distant from the tumor; (2) 50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma (HNSCC); and (3) 37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients, not exposed to smoking or alcohol consumption. Nested-polymerase chain reaction (PCR) with the MY09/11 and GP5/6 L1 primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks. All PCR reactions were performed with a positive control (cervicovaginal samples), with a negative control (Human Genomic DNA) and with a blank reaction containing all reagents except DNA. We took extreme care to prevent DNA contamination in sample collection, processing, and testing. RESULTS: The histological biopsies confirmed the diagnosis of ESCC in 52 samples (51 from ESCC group and 1 from the HNSCC group) and classified as well differentiated (12/52, 23.1%), moderately differentiated (27/52, 51.9%) or poorly differentiated (7/52, 13.5%). One hundred twenty-eight esophageal biopsies were considered normal (51 from the ESCC group, 42 from the HNSCC group and 35 from dyspeptic patients). Nine had esophagitis (7 from the HNSCC and 2 from dyspeptic patients). Of a total of 189 samples, only 6 samples had insufficient material for PCR analysis: 1 from mucosa distant from the tumor in a patient with ESCC, 3 from patients with HNSCC and 2 from patients without cancer. In 183 samples (96.8%) GAPDH, G3PDH and/or ?-globin were amplified, thus indicating the adequacy of the DNA in those samples. HPV DNA was negative in all the 183 samples tested: 52 with ESCC, 9 with esophagitis and 122 with normal esophageal mucosa. CONCLUSION: There was no evidence of HPV infection in different ESCC from southern Brazil.
Antunes, Luis Carlos Moreira; Prolla, Joao Carlos; de Barros Lopes, Antonio; da Rocha, Marta Pires; Fagundes, Renato Borges
The aim of this paper is to evaluate the methods and therapeutic principles of esophageal diverticula pathology. We analyze the main pathological mechanisms which establish the therapeutic attitude linked with a complex pretherapeutic evaluation. In our study we enrolled 12 patients operated between 2001-2009 for esophageal diverticula with different topography. In this period of time there were much more patients diagnosed with this pathology, but the need for surgery was establish very tight regarding the actual practical guide which impose the identification and interception of physiological mechanisms by the surgical procedure. We highlight the particular technical details, as well as the important differences of postoperatory complications according to the topography of the diverticula pouch. PMID:21523958
Constantinoiu, S; Constantin, A; Predescu, D; Mates, I N; Mocanu, A; Gheorghe, M; Hoar?, P; Achim, F; Cociu, L
Barrett's esophagus (BE) is the premalignant lesion from which esophageal adenocarcinoma near the esophagogastric junction arises. The management of BE and the treatment of Barrett's esophageal adenocarcinoma (BEA) are important clinical issues in Europe and the United States. As the Helicobacter pylori infection rate in Japan is decreasing in the younger population, the incidence of BE and adenocarcinoma arising from BE may start increasing. Thus, we review the current status of BEA and its management. Magnifying endoscopy with narrow-band imaging is important for diagnosing dysplasia arising from BE. In Japan, adenocarcinoma arising from BE is managed the same way as squamous cell carcinoma in the same location. Strategies to prevent BEA may include medication such as non-steroidal anti-inflammatory drugs and proton pump inhibitors, and anti-reflux surgery. Understanding the pathophysiology of BE will help to reduce the incidence of BEA. PMID:23283352
Miyazaki, Tatsuya; Inose, Takanori; Tanaka, Naritaka; Yokobori, Takehiko; Suzuki, Shigemasa; Ozawa, Daigo; Sohda, Makoto; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kuwano, Hiroyuki
Vitiligo is a disease that results in depigmented areas in the skin. It may develop at any age but the average age at onset is 20 years. Association of vitiligo and melanoma has been commonly reported, but malignancies other than melanoma have been rarely associated with vitiligo. We report a 73-year-old patient with new onset vitiligo who developed esophageal adenocarcinoma in the following years.
Asilian, Ali; Momeni, Iman; Khosravani, Parastou
Esophageal cancer remains one of the leading causes of cancer death worldwide. Patients generally present with progressive\\u000a dysphagia, malnutrition, and weight loss. The diagnosis commonly involves radiologic studies and conventional esophagogastroduodenoscopy.\\u000a Advances in endoscopic evaluation have allowed early detection of premalignant and malignant lesions. These techniques include\\u000a chromoscopy, which can be performed in conjunction with high-resolution\\/magnification endoscopy, and fluorescent endoscopy.
Darius Sorbi; David E. Fleischer
Objective: Symptoms of pediatric eosinophilic esophagitis (EoE) include dysphagia, emesis, regurgitation and feeding difficulties. This symptom complex has been mistaken for refractory gastroesophageal reflux disease (GERD). Whether EoE and GERD are related is controversial. Recently, EoE has been associated with upper airway manifestations including recurrent sinusitis, cough, wheezing, pneumonia, laryngeal edema, and subglottic stenosis. Laryngospasm secondary to EoE has not
Carrie L. Francis; Troy Gibbons; Gresham T. Richter
Eosinophilic esophagitis (EE) is a newly recognized disease, which has largely been called idiopathic EE, emphasizing the poor understanding of its pathogenesis. EE is a severe disease of the esophagus characterized by an accumulation of eosinophils in the esophageal mucosa. EE is highly associated with atopic disease and emerging evidence suggests a primary role for food antigen sensitization in disease etiology. Nevertheless, the nomenclature “Eosinophilic esophagitis” describes only the surface of the iceberg of a complex disorder. Epithelial cells, fibroblasts, endothelial cells and smooth muscles cells are involved in pathologic features of the disease and numerous leukocyte subtypes are recruited (eosinophils, mast cells, lymphocytes). As such, the pathogenesis of EE involves multiple tissues, cell types, genes and derives from complex genetic and environmental factors. “Pathogenesis” is a fusion of two Greek words pathos (disease) and genesis (development). In this review, we aim to define the fundamental piece of knowledge available today that characterizes the mechanisms by which certain etiological factors cause EE, reviewing human studies, murine models and recent knowledge regarding the involvement of environmental, cellular, molecular and genetic factors in the development of EE.
Blanchard, Carine; Rothenberg, Marc E.
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.
Lunderquist, A.; Owman, T.; Alwmark, A.; Gullstrand, P.; Hall-Angeras, M.; Joelsson, B.; Tranberg, K.G.; Pettersson, K.I.
Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) is the most common congenital anomaly of the esophagus. The improvement of survival observed over the previous two decades is multifactorial and largely attributable to advances in neonatal intensive care, neonatal anesthesia, ventilatory and nutritional support, antibiotics, early surgical intervention, surgical materials and techniques. Indeed, mortality is currently limited to those cases with coexisting severe life-threatening anomalies. The diagnosis of EA is most commonly made during the first 24 h of life but may occur either antenatally or may be delayed. The primary surgical correction for EA and TEF is the best option in the absence of severe malformations. There is no ideal replacement for the esophagus and the optimal surgical treatment for patients with long-gap EA is still controversial. The primary complications during the postoperative period are leak and stenosis of the anastomosis, gastro-esophageal reflux, esophageal dysmotility, fistula recurrence, respiratory disorders and deformities of the thoracic wall. Data regarding long-term outcomes and follow-ups are limited for patients following EA/TEF repair. The determination of the risk factors for the complicated evolution following EA/TEF repair may positively impact long-term prognoses. Much remains to be studied regarding this condition. This manuscript provides a literature review of the current knowledge regarding EA.
Pinheiro, Paulo Fernando Martins; Simoes e Silva, Ana Cristina; Pereira, Regina Maria
Investigations and technical advances have enhanced our understanding and management of gastroesophageal reflux disease. The recognition of the prevalence and importance of patients with endoscopy-negative reflux disease as well as those refractory to proton pump inhibitor therapy have led to an increasing need for objective tests of esophageal reflux. Guidelines for esophageal reflux testing are developed under the auspices of
Ikuo Hirano; Joel E. Richter
There have so far been few reports on esophageal diverticulum in children. We experienced two symptomatic pediatric cases with esophageal diverticulum. Our cases manifested high fever and dysphagia with chest pain during swallowing. The patients underwent endoscopic diverticulotomy. The septum between the diverticulum and the esophagus was cut using the argon plasma coagulation (APC 3000) system. We recommend an endoscopic diverticulotomy
Y. Nishimoto; T. Taguchi; K. Ogita; M. Hashizume; S. Suita
Gastro-esophageal reflux disease encompasses a spectrum of disorders in which gastric reflux leads to symptoms and\\/or damage to the esophageal mucosa. Although a common problem in clinical practice, our understanding of the pathophysiology of the condition has not been matched by our knowledge of its epidemiology and natural history. This review examines some of the difficulties inherent in epidemiological studies
P. J. Howard; R. C. Heading
The objective of the study reported here was to characterise the microscopic appearance of peptic-injured equine gastric squamous epithelium in relation to the duration of peptic injury. Erosions and ulcers were induced in equine gastric squamous epithelium using a feed deprivation protocol that results in prolonged increased gastric acidity. Specimens of normal gastric mucosa and mucosa with lesions created after 48 and 96 h of feed deprivation were compared for characteristics associated with angiogenesis and mucosal proliferation. Fifteen mature horses, 9 geldings and 6 mares, age 3-20 years, were divided into 3 groups. Group 1 (n = 5) had normal-appearing gastric squamous mucosal epithelium and had been killed due to problems unrelated to the gastrointestinal tract. Groups 2 (n = 5) and 3 (n = 5) had lesions induced in the gastric squamous epithelium by alternating 24 h periods of feed deprivation and ad libitum access to hay, for totals of 48 and 96 h feed deprivation, respectively. Following lethal injection of barbiturate, stomachs were removed and fixed by filling with 4-6 l 10% buffered formalin. Sections were made from lesions in the gastric squamous epithelium adjacent to the margo plicatus along the right side of the stomach/greater curvature and the lesser curvature. Measurements of total epithelial thickness, keratinised epithelium, nonkeratinised epithelium, epithelial projections, capillary extension into the epithelium and lamina propria thickness were made. The cross-sectional areas of arterial and venous vascular structures in the lamina propria at the lesions and their margins were measured using image analysis software. All horses, except one, in Group 2 developed erosions or ulcers in the gastric squamous epithelium after feed deprivation. There were several changes in the epithelium adjacent to erosions and ulcers, compared to normal epithelium, from horses in Groups 2 and 3: total epithelial thickness was significantly (P<0.05) greater, including both keratinised and nonkeratinised layers in most specimens; the length of epithelial projections and extent to which capillaries from the lamina propria extended toward the luminal surface, and the cross-sectional area of vascular structures (arterioles, capillaries, venules) in the lamina propria were significantly greater. Epithelial thickness of erosion beds was not significantly less than normal epithelium, although a greater proportion of the epithelium in erosions consisted of epithelial projections (Group 1, 23%; Group 2, 76%; Group 3, 72%). The cross-sectional area of vascular structures in the lamina propria beneath erosions was significantly greater than in normal mucosa only in Group 2 tissues, whereas in the lamina propria of ulcers it was significantly greater than in normal mucosa only in Group 3 tissues. The epithelial proliferation and increased vascular cross-sectional area in the lamina propria associated with peptic-induced gastric lesions are consistent with processes associated with the initiation of ulcer healing, and these changes temporally coincided with the initiation of peptic insult to the gastric squamous epithelium. These findings demonstrate that processes that promote ulcer healing begin soon after peptic injury and that they progress even with repeated peptic injury. Furthermore, our findings support observations that gastric ulcers often heal without medical intervention, and the theory that medications that reduce gastric acidity do not initiate healing, but rather facilitate ulcer healing by providing a microenvironment that is optimal for healing to proceed. PMID:11720026
Murray, M J; Eichorn, E S; Jeffrey, S C
We describe the clinical and pathologic features of a hitherto unreported finding in patients with esophagitis: the presence of multinucleated squamous epithelial giant cells simulating viral cytopathic effect and/or dysplasia. Routinely processed hematoxylin and eosin (H&E)-stained slides of esophageal mucosal biopsies from 14 patients with both active esophagitis and multinucleated epithelial giant cells were evaluated for a variety of inflammatory and epithelial features. Clinical, endoscopic, and follow-up data were collected and correlated with the histologic findings. Immunostaining (ABC method) for cytokeratin AE1/AE3, S-100, MIB-1, herpes simplex virus 1 and 2 (HSV), cytomegalovirus (CMV), as well as DNA in situ hybridization for human papilloma virus (HPV-ISH) was performed in all cases. Electron microscopic evaluation for viral particles was performed in three cases. The study group consisted of nine men and five women (mean age 59 years; range 23-87 years; 12 white, one black, one Hispanic). Patients presented with dysphagia or odynophagia (n = 5), upper gastrointestinal bleeding (n = 5), heartburn (n = 2), or abdominal pain (n = 2). The etiology of esophagitis was attributed to gastroesophageal reflux in 10, radiotherapy in one, Candida infection in one, drug-induced (alendronate) in one, and unknown in 1. Endoscopically, seven patients had an ulcer or erosion, four erythema, two stricture formation, and one white mucosal plaques. Microscopically, all cases showed multiple multinucleated (mean three nuclei per cell, range two to nine) squamous epithelial cells (range 2 to 11 cells per biopsy) confined to the basal zone in nine of 14 cases and involving the basal and superficial epithelium in the remainder. The nuclei contained a single or multiple eosinophilic nucleoli with a perinucleolar halo, but no inclusions, hyperchromaticity, or atypical mitoses. All cases showed associated nonspecific features of active esophagitis such as ulceration, neutrophilic and eosinophilic inflammation, basal cell hyperplasia, and elongation of the lamina propria papillae. The multinucleated giant cells, in all cases, were strongly positive for cytokeratin AE1/AE3 and were negative for S-100, HSV I and II, CMV, and HPV-ISH. MIB-1 positivity was observed in all basally located multinucleated giant cells, whereas those in the more superficial layers were negative. Electron microscopy failed to show viral particles in three of three cases. After treatment, all patients demonstrated clinical improvement. Three patients in whom follow-up biopsies were performed showed no evidence of esophagitis, epithelial cell multinucleation, or dysplasia. Multinucleated epithelial giant cell changes may rarely be seen in patients with esophagitis of varying etiology and probably represent a regenerative response to injury. This feature is important to distinguish from either viral cytopathic effect or dysplasia. PMID:9422321
Singh, S P; Odze, R D
Eosinophilic esophagitis is a chronic, clinically and histologically defined, inflammatory condition of the esophagus. The histological hallmark of eosinophilic esophagitis is a relevant, often patchy infiltration of the esophageal mucosa with eosinophils. In a consensus report a threshold value of approximately 120 eosinophils per mm(2) was arbitrarily fixed as a diagnostic criterion. Noteworthy for the quantification of the eosinophilic infiltration are several technical facts, for instance size and covering extent of the biopsy specimen of the high-power field (hpf) and quality of embedding of biopsy specimens have to be considered. In order to establish the histological diagnosis several additional abnormalities must be included in the assessment and gastrointestinal reflux disease is the main differential diagnosis of eosinophilic esophagitis. Finally it is emphasized that for an affirmative diagnosis of eosinophilic esophagitis, in addition to the histological findings the clinical facts must be included. PMID:23483314
Bussmann, C; Straumann, A
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
Hotelling, Barbara A
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.
Hotelling, Barbara A
Background The feasibility of evaluating an objective grading of cervical intraneoplasia lesions (CIN) is attempted using an automatic computerized system able to measure several valuable parameters with special reference to epithelium differentiation. Methods 4 groups of 10 images each were selected at random from 68 consensus images coming from 80 archival cervical biopsies, normal (n = 10), CIN 1 (n = 10), CIN 2 (n = 10), CIN 3 (n = 10). Representative images of lesions were captured from the microscopic slides and were analyzed using mathematical morphology, with special reference toVoronoï tessellation and Delaunay triangulation. Epithelium surface, nuclear and cytoplasm area, triangle edge and area, total and upper nuclear index were precisely measured in each lesion, and discriminant coefficients were calculated therewith. A dilation/erosion coefficient was automatically defined using triangle edge length and nuclear radius in order to measure the epithelium ratio of differentiation. A histogram ratio was also automatically established between total nuclei and upper nuclei on top of differentiated epithelium. With the latter two ratios added to the nucleo-cytoplasmic ratio, a cervical score able to classify CIN is proposed. Results There is a quasi-linear increase of mean cervical score values between normal epithelium and CIN 3: (27) for normal epithelium, (51) for CIN 1, (78) for CIN 2 and (100) for CIN 3, with significant differences (P < 0.05). Conclusion Our results highlight the possibility of applying a cervical score for the automatic grading of CIN lesions and thereby assisting the pathologist for improvement of grading. The automatic measure of epithelium differentiation ratio appears to be a new interesting parameter in computerized image analysis of cervical lesions.
Background: The normal systemic inflammatory response to surgical stimuli often makes early diagnosis of postoperative infections difficult. Purpose: We investigated whether serum procalcitonin (PCT) levels may be a useful marker of bacterial infections in patients after invasive surgery. Subjects and Methods: The subjects were 40 patients who had undergone radical surgery for esophageal carcinoma by a right thoracoabdominal approach. Nine
S. Ito; N. Sato; M. Kojika; Y. Yaegashi; Y. Suzuki; K. Suzuki; S. Endo
Homeobox genes function as master regulators in embryonic morphogenesis. We hypothesized that homeobox genes are essential to maintain tissue- or organ-specificity even in adult body and that the dysregulated expression of homeobox genes results in tumor development and progression. To better understand the roles of homeobox genes in development and progression of esophageal cancer, we analyzed the expression patterns of 39 HOX genes and 4 ParaHOX (CDX1, CDX2, CDX4 and PDX1) genes in esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa tissues. A total of 48 primary ESCC tissues and 7 normal esophageal mucosa tissues were resected from patients who underwent radical surgery without any preoperative chemotherapy or radiotherapy. The expression of HOX and ParaHOX genes were analyzed by a quantitative real-time RT-PCR method and immunohistochemistry. The expression levels of 24 HOX genes, CDX1, CDX2 and PDX1 were significantly higher in ESCC compared to normal mucosa (p<0.01, Mann-Whitney U test). The Immunohistochemical study revealed that HOXA5 and D9 proteins were more cytoplasmic in ESCC than normal mucosa cells. Our data indicate that the disordered expression of HOX and ParaHOX genes are involved in the development of ESCC or its malignancy. PMID:17342311
Takahashi, Osamu; Hamada, Jun-Ichi; Abe, Motoki; Hata, Shinya; Asano, Toshimichi; Takahashi, Yoko; Tada, Mitsuhiro; Miyamoto, Masaki; Kondo, Satoshi; Moriuchi, Tetsuya
While neoplastic lesions of the retinal pigment epithelium (RPE) are exceedingly rare, benign reactive proliferations of this tissue are frequently observed as a result of a variety of stimuli, including trauma, retinal detachment, high myopia, disciform ...
B. S. Fine L. E. Zimmerman R. L. Font
This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-?, interleukin (IL)-1? and IL-6 were all assayed and the expression of TNF-? and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of ?-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-?, IL-1? and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-? and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with ?-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-? in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage. PMID:23227795
Ku, Sae-Kang; Kim, Jae-Soo; Seo, Young-Bae; Kim, Yong-Ung; Hwang, Seung-Lark; Lee, Young-Chul; Yang, Chae-Ha; Kim, Hui-Young; Seo, Bu-Il; Park, Ji-Ha; Min, You-Hong; Roh, Seong-Soo
TGF-? and Notch signaling pathways play important roles in regulating self-renewal of stem cells and gastrointestinal carcinogenesis. Loss of TGF-? signaling components activates Notch signaling in esophageal adenocarcinoma, but the basis for this effect has been unclear. Here we report that loss of TGF-? adapter ?2SP (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 ?2SP 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 ?2SP 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 ?2SP-silenced esophageal adenocarcinoma cells. Conversely, SOX9 silencing rescued the phenotype of esophageal adenocarcinoma cells with loss of ?2SP. Interaction between Smad3 and ICN1 via Smad3 MH1 domain was also observed, with loss of ?2SP increasing the binding between these proteins, inducing expression of Notch targets SOX9 and C-MYC, and decreasing expression of TGF-? targets p21(CDKN1A), p27 (CDKN1B), and E-cadherin. Taken together, our findings suggest that loss of ?2SP switches TGF-? signaling from tumor suppression to tumor promotion by engaging Notch signaling and activating SOX9.
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
Objective. This report describes 3 cases of ciliated epithelium-lined radicular cysts among 256 apical periodontitis lesions and also illustrates the occurrence of an Actinomyces-infected periapical cyst. Study Design. Serial and step serial sections of 256 plastic-embedded root apices with attached apical periodontitis lesions that were prepared for a previous investigation were reviewed for the presence of ciliated epithelium-lined radicular cysts.
P. N. Ramachandran Nair; Gion Pajarola; Hans-Ulrich Luder
Serological diagnosis of bullous pemphigoid is based on immunoblotting or indirect immunofluorescence on normal human salt-split skin. These methods are expensive or time-consuming and not available as a routine test in all laboratories. We used rat bladder epithelium as substrate for indirect immunofluorescence and compared it with other substrates and with immunoblotting. Twenty-nine bullous pemphigoid sera were studied on rat bladder epithelium, monkey oesophagus, salt-split skin and with immunoblotting on human keratinocyte cultures. Indirect immunofluorescence on rat bladder epithelium proved to be more sensitive (72%) than on monkey oesophagus alone (45%) and less sensitive than on salt-split skin (97%). Rat bladder epithelium, when tested on 41 sera of a control group, showed a very high specificity: 2/41 (95%). In combination with immunoblotting on keratinocyte extracts, indirect immunofluorescence on rat bladder epithelium allowed 93% of sera to be recognized, a value close to the salt-split skin alone. Rat bladder epithelium appears to be a more sensitive substrate than monkey oesophagus for the diagnosis of bullous pemphigoid and, although less specific, it is easier and faster than using salt-split skin, which remains indispensable to distinguish bullous pemphigoid from epidermolysis bullosa acquisita. PMID:10954206
Delmonte, S; Cozzani, E; Drosera, M; Parodi, A; Rebora, A
Keratinocytes are the predominant cells in human skin. As keratinocytes differentiate, the nuclei are lost and the cornified cell envelope (CCE) develops, forming a covalently cross-linked, insoluble structure under the cell membrane. Layers of anuclear CCEs in the stratum corneum provide a barrier against water loss and mechanical damage and are a first line of immunologic defense. Infection of keratinocytes with human papillomaviruses (HPVs) induces proliferation and abnormalities including retention of nuclei in the stratum corneum and perinuclear halo formation. For effective transmission, HPV virions must be released from the CCE, a normally very durable structure. Therefore, it is likely that HPV infection affects the CCE in a manner that would facilitate virion release. To investigate the effects of HPV 11 infection on morphology and fragility, CCEs were purified from infected and uninfected epithelium. CCEs isolated from uninfected epithelium were smooth, cuboidal, and sonicated into long coiled structures. In contrast, CCEs from HPV 11-infected epithelium were irregular in size and shape, with rough edges, and sonicated into small fragments. In addition, the thickness of CCEs from HPV 11-infected tissue was 65% that of uninfected epithelium. Immunohistochemical analysis demonstrated that in contrast to uninfected epithelium, loricrin, the major component of the CCE, was abnormally distributed in the differentiated layers of HPV 11-infected epithelium. We conclude that in addition to the previously described epithelial abnormalities induced by HPV, the CCE is also affected by infection in ways that may facilitate transmission of virus from person to person. PMID:10814571
Brown, D R; Bryan, J T
The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix. The two principal methods available for esophageal varices are endoscopic sclerotherapy (EST) and band ligation (EBL). The advantages of EST are that it is cheap and easy to use, and the injection catheter fits through the working channel of a diagnostic gastroscope. Endoscopic variceal ligation obliterates varices by causing mechanical strangulation with rubber bands. The following review aims to describe the utility of EBL and EST in different situations, such as acute bleeding, primary and secondary prophylaxis. PMID:22816012
Poza Cordon, Joaquin; Froilan Torres, Consuelo; Burgos García, Aurora; Gea Rodriguez, Francisco; Suárez de Parga, Jose Manuel
We have shown that ECRG4 suppressed Fas-induced apoptosis in Jurkat cells. ECRG4 mRNA expression was ubiquitously detected in normal adult human tissues, suggesting that ECRG4 plays a major role in human tissues. ECRG4 mRNA expression was down-regulated in tumor cells. Expression of ECRG4 suppressed cell growth. We established an anti-ECRG4 monoclonal antibody. Our immunohistochemical analysis demonstrated that ECRG4-positive cells tended to be distributed in the region that was negative for Ki-67 in esophageal squamous cell carcinoma tissues. There was a significant inverse correlation between ECRG4 expression and Ki-67 labeling index in esophageal squamous cell carcinoma. This study provides the first functional evidence for an association of endogenous expression of ECRG4 with cell proliferation. ECRG4 is a candidate tumor suppressor gene that might be involved in the proliferation of esophageal squamous cell carcinoma. PMID:23957914
Matsuzaki, Junichi; Torigoe, Toshihiko; Hirohashi, Yoshihiko; Tamura, Yasuaki; Asanuma, Hiroko; Nakazawa, Emiri; Saka, Eri; Yasuda, Kazuyo; Takahashi, Shuji; Sato, Noriyuki
Multichannel intraluminal impedance (MII) for the evaluation of esophageal diseases was created in 1991 trying to solve previous limitations of esophageal function test. MII-pH is able to determine the physical characteristics of the refluxate (liquid, gas, or mixed) and nonacidic GER. MII-manometry can determine the presence of bolus and its relation with peristalsis. This paper makes a critical analysis of the clinical applications of MII 20 years after its creation. Literature review shows that MII made great contributions for the understanding of esophageal physiology; however, direct clinical applications are few. MII-pH was expected to identify patients with normal acid reflux and abnormal nonacidic reflux. These patients are rarely found off therapy, that is, nonacidic reflux parallels acid reflux. Furthermore, the significance of isolated nonacidic reflux is unclear. Contradictory MII-manometry and conventional manometry findings lack better understanding and clinical implication as well as the real significance of bolus transit.
Herbella, Fernando A. M.
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.
Arya, Ekta; Saha, Sudipta; Saraf, Shubhini A.; Kaithwas, Gaurav
Intragastric pressure measurements and cineradiographic contrast studies were done in monkeys in order to determine the pressure at which esophageal reflux occurred. Antireflux operative procedures were performed above and below the diaphragm, and the results compared. The Nissen fundoplication proved to be the most effective type of mechanical antireflux valve and worked equally well placed above and below the diaphragm. Of 200 consecutive adult patients undergoing operative correction of esophageal reflux, 19 had severe esophageal strictures. Through a transthoracic approach, two patients had subdiaphragmatic Nissen fundoplications, one with adenocarcinoma of the esophagus had an esophageal resection, and 16 had supradiaphragmatic Nissen fundoplications; those 16 patients form the basis of this report. No patients died; superficial, temporary esophageal ulcerations developed in two. Follow-up times have ranged from six months to eight years; the results in all cases have been good. Experimental and clinical evidence supports the belief that this less radical approach is the treatment of choice in the management of severe esophageal strictures secondary to reflux esophagitis. Images Fig. 1. Fig. 2. Figs. 3. and 4. Figs. 5-7. Figs. 8. and 9. Fig. 10. Figs. 11. and 12.
Pennell, T C
Esophageal carcinoma is one of the deadliest cancers with highly aggressive potency, ranking as the sixth most common cancer among males and ninth most common cancer among females globally. Due to metastasis and invasion of surrounding tissues in early stage, the 5-year overall survival rate (14%) of esophageal cancer remains poor, even in comparison with the dismal survival rates (4%) from the 1970s. Numerous genes and proteins with abnormal expression and function involve in the pathogenesis of esophageal cancer, but the concrete process remains unclear. Microarray technique has been applied to investigating esophageal cancer. Many gene expression studies have been undertaken to look at the specific patterns of gene transcript levels in esophageal cancer. Human tissues and cell lines were used in these geneprofiling studies and a very valuable and interesting set of data has resulted from various microarray experiments. These expression studies have provided increased understanding of the complex pathological mechanisms involved in esophageal cancer. The eventual goal of microarray is to discover new markers for therapy and to customize therapy based on an individual tumor genetic composition. This review summarized the current state of gene expression profile studies in esophageal cancer.
Guo, Wei; Jiang, Yao-Guang
Esophageal cancer incidence is increasing and has few treatment options. In studying receptor tyrosine kinases associated with esophageal cancers, we have identified EPHB4 to be robustly overexpressed in cell lines and primary tumor tissues. In total, 94 squamous cell carcinoma, 82 adenocarcinoma, 25 dysplasia, 13 Barrett esophagus, and 25 adjacent or unrelated normal esophageal tissues were evaluated by immunohistochemistry. EPHB4 expression was significantly higher in all the different histologic categories than in adjacent normal tissues. In 13 esophageal cancer cell lines, 3 of the 9 SCC cell lines and 2 of the 4 adenocarcinomas expressed very high levels of EPHB4. An increased gene copy number ranging from 4 to 20 copies was identified in a subset of the overexpressing patient samples and cell lines. We have developed a novel 4-nitroquinoline 1-oxide (4-NQO)-induced mouse model of esophageal cancer that recapitulates the EPHB4 expression in humans. A specific small-molecule inhibitor of EPHB4 decreased cell viability in a time- and dose-dependent manner in 3 of the 4 cell lines tested. The small-molecule inhibitor and an EPHB4 siRNA also decreased cell migration (12%-40% closure in treated vs. 60%-80% in untreated), with decreased phosphorylation of various tyrosyl-containing proteins, EphB4, and its downstream target p125FAK. Finally, in a xenograft tumor model, an EPHB4 inhibitor abrogated tumor growth by approximately 60% compared with untreated control. EphB4 is robustly expressed and potentially serves as a novel biomarker for targeted therapy in esophageal cancers. PMID:23100466
Hasina, Rifat; Mollberg, Nathan; Kawada, Ichiro; Mutreja, Karun; Kanade, Geetanjali; Yala, Soheil; Surati, Mosmi; Liu, Ren; Li, Xiuqing; Zhou, Yue; Ferguson, Benjamin D; Nallasura, Vidya; Cohen, Kenneth S; Hyjek, Elizabeth; Mueller, Jeffery; Kanteti, Rajani; El Hashani, Essam; Kane, Dorothy; Shimada, Yutaka; Lingen, Mark W; Husain, Aliya N; Posner, Mitchell C; Waxman, Irving; Villaflor, Victoria M; Ferguson, Mark K; Varticovski, Lyuba; Vokes, Everett E; Gill, Parkash; Salgia, Ravi
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
Montoya, Manuel; Chumbiraico, Robert; Ricalde, Melvin; Cazorla, Ernesto; Hernández-Córdova, Gustavo
Recent progress has enlightened the involvement of Hox genes in organogenesis. Several Hox genes are expressed in normal and neoplastic mammary glands. Using Hoxa5 mutant mice, we showed that Hoxa5-/- females present nursing defects. Characterization of the Hoxa5-/- mammary gland phenotype reveals changes in proliferation and differentiation of the epithelium of nulliparous and pregnant Hoxa5-/- females that precede the abnormal secretory activity at parturition. These defects likely underlie the incapacity of Hoxa5-/- dams to properly feed their pups. Hoxa5 expression is restricted to the mammary stroma at specific stages of mammary gland development. The loss of Hoxa5 function causes accelerated lobuloalveolar epithelium development, a phenotype that can be rescued upon grafting of mutant mammary epithelium into wild-type fat pads. Conversely, reciprocal grafting experiments demonstrate that Hoxa5-/- stroma cannot support normal proliferation of wild-type mammary epithelium. These data establish the essential contribution of Hoxa5 to mammary epithelium instruction by means of mesenchymal-epithelial crosstalk. PMID:16607641
Garin, Elisabeth; Lemieux, Margot; Coulombe, Yan; Robinson, Gertraud W; Jeannotte, Lucie
Introduction Lower esophageal sphincter (LES) lift seen on high resolution manometry (HRM) is a possible surrogate marker of the longitudinal muscle contraction of the esophagus. Recent studies suggest that longitudinal muscle contraction of the esophagus induces LES relaxation. Aim Our goal was to determine, 1) the feasibility of prolonged ambulatory HRM and 2) to detect LES lift with LES relaxation using ambulatory HRM color isobaric contour plots. Methods In vitro validation studies were performed to determine the accuracy of HRM technique in detecting axial movement of the LES. Eight healthy normal volunteers were studied using a custom designed HRM catheter and a 16 channel data recorder, in the ambulatory setting of subject’s home environment. Color HRM plots were analyzed to determine the LES lift during swallow-induced LES relaxation as well as during complete and incomplete transient LES relaxations. Results Satisfactory recordings were obtained for 16 hours in all subjects. LES lift was small (2 mm) in association with swallow-induced LES relaxation. LES lift could not be measured during complete transient LES relaxations (TLESR) because the LES is not identified on the HRM color isobaric contour plot once it is fully relaxed. On the other hand, LES lift, mean 7.6 ± 1.4 mm, range 6–12 mm was seen with incomplete TLESRs (n = 80). Conclusions Our study demonstrates the feasibility of prolonged ambulatory HRM recordings. Similar to a complete TLESR, longitudinal muscle contraction of the distal esophagus occurs during incomplete TLESRs, which can be detected by the HRM. Using prolonged ambulatory HRM, future studies may investigate the temporal correlation between abnormal longitudinal muscle contraction and esophageal symptoms.
Mittal, Ravinder K.; Karstens, Anna; Leslie, Eric; Babaei, Arash; Bhargava, Valmik
The ovarian surface epithelium and that of related inclusion cysts were studied in 50 women with ovarian polycystic disease and they were compared with our preceding observations performed on women with endometrial carcinoma (n = 50) and on women without any hyperplastic or neoplastic genital tract pathology (n = 50). In 16 women (32%) the ovarian epithelium with normal aspect was found on the surface of the ovary and in inclusion cysts. In the remaining 34 women (68%) surface papillomatosis, hyperplastic and metaplastic changes were present on the ovarian surface and/or in the inclusion cysts. These findings were similar to those observed in the group of women with endometrial adenocarcinoma, while the surface epithelium was often normal in the control group. Our observations confirm the hypothesis of a hormonal influence in the hyperplastic and metaplastic modifications of the ovarian epithelium and in the related common epithelial tumors of the ovary. PMID:2917579
Resta, L; Scordari, M D; Colucci, G A; Faggiano, C; Loizzi, P; Di Gesù, A; Borraccino, V; Conte, R; Milillo, F
Light microscopy (including fluorescence microscopy) and electron microscopy were applied to a study of the photoreceptor-retinal pigment epithelium (RPE) complex in a human eye which had been severely traumatised nine months prior to enucleation. The main feature of interest was a massive accumulation of lipofuscin in the retinal pigment epithelium at the posterior pole, and quantitative fluorescence microscopy provided values three times those obtained in appropriate control tissue. The photoreceptor layer was normal at the posterior pole but became progressively atrophic towards the periphery. The concentration of lipopofuscin was proportional to the degree of preservation of the retinal photoreceptors. By electron microscopy the cells in the RPE were seen to be packed with a mixture of lipofuscin granules and melanolysosomal complexes, but occasional photoreceptor phagosomes were found. Bruch's membrane and the choriocapillaris were normal. We attribute this hitherto unreported abnormality of the RPE after trauma to a dysfunction consequent on an overload of the monolayer by photoreceptor debris at the time of trauma. Images
Ko, M K; Lee, W R; McKechnie, N M; Hall-Parker, B
Esophageal motor function is highly coordinated between central and enteric nervous systems and the esophageal musculature, which consists of proximal skeletal and distal smooth muscle in three functional regions, the upper and lower esophageal sphincters, and the esophageal body. While upper endoscopy is useful in evaluating for structural disorders of the esophagus, barium esophagography, radionuclide transit studies, and esophageal intraluminal impedance evaluate esophageal transit and partially assess motor function. However, esophageal manometry is the test of choice for the evaluation of esophageal motor function. In recent years, high-resolution manometry (HRM) has streamlined the process of acquisition and display of esophageal pressure data, while uncovering hitherto unrecognized esophageal physiologic mechanisms and pathophysiologic patterns. New algorithms have been devised for analysis and reporting of esophageal pressure topography from HRM. The clinical value of HRM extends to the pediatric population, and complements preoperative evaluation prior to foregut surgery. Provocative maneuvers during HRM may add to the assessment of esophageal motor function. The addition of impedance to HRM provides bolus transit data, but impact on clinical management remains unclear. Emerging techniques such as 3-D HRM and impedance planimetry show promise in the assessment of esophageal sphincter function and esophageal biomechanics. PMID:23336590
Gyawali, C P; Bredenoord, A J; Conklin, J L; Fox, M; Pandolfino, J E; Peters, J H; Roman, S; Staiano, A; Vaezi, M F
Glycosylated structures on the cell surface have a role in cell adhesion, migration, and proliferation. Repair of the airway epithelium after injury requires each of these processes, but the expression of cell surface glycosylation of airway epithelial cells after injury is not known. We examined cell surface glycosylation using lectin-binding profiles of normal and repairing epithelia in Hartley guinea pigs
Xiantang Li; Delbert R. Dorscheid; Kimberly R. Wojcik; Steven R. White
Glycosylated structures on the cell surface have a role in cell adhesion, migration, and proliferation. Repair of the airway epithelium after injury requires each of these processes, but the normal cell surface glycosylation of non-mucin producing airway epithelial cells is unknown. We examined cell surface glycosylation in human airway epithelial cells in tissue sections and in human airway epithelial cell
Delbert R. Dorscheid; Amber E. Conforti; Kimm J. Hamann; Klaus F. Rabe; Steven R. White
Nonviral vectors have been shown to be a safe and valid alternative to recombinant viruses for gene therapy of cystic fibrosis (CF). Nevertheless, gene transfer efficiency needs to be increased before clinical efficacy is likely in man. One barrier to increased efficacy is normal airway mucus. Using an ex vivo model of sheep tracheal epithelium, we show that this barrier
S Ferrari; C Kitson; R Farley; R Steel; C Marriott; DA Parkins; M Scarpa; B Wainwright; MJ Evans; WH Colledge; DM Geddes; EWFW Alton
In three experiments, the authors have explored the uptake and transport of collidal gold (Au) and iron oxide (Fe2O3) by normal and SO2-injured bronchial epithelium. In the first experiment mice were exposed to a 2-hr aerosol of Au; in the second experiment, mice were exposed to ...
Twenty-two patients with esophageal carcinoma had no local recurrence after external and intracavitary radiation treatment, but all developed ulcers in the field of intracavitary irradiation. Ten were linear ulcers that appeared 3-12 months after radiation treatment (mean, 5.3 months); the other 12 were the long circumferential type and appeared 1-8 months after irradiation (mean, 3.7 months). Esophagobronchial fistulae developed in two cases in which deep ulcer had been found between the completion of external irradiation and the beginning of intracavitary irradiation. In these cases with deep ulcer, intracavitary irradiation should not be done. For patients receiving intracavitary radiation, the total dosage should be less than 20 Gy.
Hishikawa, Y.; Tanaka, S.; Miura, T.
...SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Prosthetic Devices Â§ 878.3610 Esophageal...rigid, flexible, or expandable tubular device made of a plastic, metal, or polymeric material that is...
Tracheoesophageal fistula and esophageal atresia repair is surgery to repair two birth defects in your esophagus and trachea. ... not connect with the lower esophagus and stomach. Tracheoesophageal fistula (TEF) is a connection between the upper part ...
Gastroesophageal reflux disease is a risk factor for esophageal adenocarcinoma yet studies that have investigated the relationship between erosive esophagitis and esophageal adenocarcinoma have usually focused on symptom-related evidence or polymorphisms. There are no epigenetic gene expression studies on this topic. In this study, we aimed to evaluate the relationship between erosive esophagitis and esophageal adenocarcinoma to identify whether there is a genetic predisposition for esophageal adenocarcinoma. The Human Epigenetic Chromatin Modification Enzyme RT(2) Profiler(™) PCR array (PAHS-085A) was used to detect the expression of 84 key genes encoding enzymes. This was carried out prospectively for samples from 60 patients (20 patients as a control group, 20 patients with erosive esophagitis and 20 patients with esophageal adenocarcinoma). AURKA, AURKB, NEK6 were expressed at significantly higher levels in esophageal adenocarcinoma compared to the control group. MBD2 was expressed at significantly lower levels in the esophageal adenocarcinoma group compared to the control group. AURKA, AURKC, HDAC9 and NEK6 were expressed at significantly higher levels in erosive esophagitis compared to the control group. There was no difference in upregulated gene expression between the erosive esophagitis and esophageal adenocarcinoma. MBD2 was significantly downregulated in esophageal adenocarcinoma compared to erosive esophagitis. NEK6 and AURKA were significantly upregulated in esophageal adenocarcinoma and erosive esophagitis compared to the control group. This is a novel study on the genetic predisposition for erosive esophagitis and esophageal adenocarcinoma. AURKA and NEK6 are two promising genetic markers for erosive esophagitis and esophageal adenocarcinoma. PMID:23060919
Kasap, Elmas; Boyacioglu, Seda Örenay; Korkmaz, Mehmet; Yuksel, Elif Saritas; Unsal, Belkis; Kahraman, Erkan; Ozütemiz, Omer; Yuceyar, Hakan
Gastroesophageal reflux disease is a risk factor for esophageal adenocarcinoma yet studies that have investigated the relationship between erosive esophagitis and esophageal adenocarcinoma have usually focused on symptom-related evidence or polymorphisms. There are no epigenetic gene expression studies on this topic. In this study, we aimed to evaluate the relationship between erosive esophagitis and esophageal adenocarcinoma to identify whether there is a genetic predisposition for esophageal adenocarcinoma. The Human Epigenetic Chromatin Modification Enzyme RT2 Profiler™ PCR array (PAHS-085A) was used to detect the expression of 84 key genes encoding enzymes. This was carried out prospectively for samples from 60 patients (20 patients as a control group, 20 patients with erosive esophagitis and 20 patients with esophageal adenocarcinoma). AURKA, AURKB, NEK6 were expressed at significantly higher levels in esophageal adenocarcinoma compared to the control group. MBD2 was expressed at significantly lower levels in the esophageal adenocarcinoma group compared to the control group. AURKA, AURKC, HDAC9 and NEK6 were expressed at significantly higher levels in erosive esophagitis compared to the control group. There was no difference in upregulated gene expression between the erosive esophagitis and esophageal adenocarcinoma. MBD2 was significantly downregulated in esophageal adenocarcinoma compared to erosive esophagitis. NEK6 and AURKA were significantly upregulated in esophageal adenocarcinoma and erosive esophagitis compared to the control group. This is a novel study on the genetic predisposition for erosive esophagitis and esophageal adenocarcinoma. AURKA and NEK6 are two promising genetic markers for erosive esophagitis and esophageal adenocarcinoma.
KASAP, ELMAS; BOYACIOGLU, SEDA ORENAY; KORKMAZ, MEHMET; YUKSEL, ELIF SARITAS; UNSAL, BELKIS; KAHRAMAN, ERKAN; OZUTEMIZ, OMER; YUCEYAR, HAKAN
. A case of necrotizing esophagitis discovered during upper endoscopy is described. An 88-year-old woman was admitted to our\\u000a hospital with complaints of multiple episodes of coffee ground emesis and dysphagia over 3 months. Ischemia is proposed as\\u000a the etiology of necrotizing esophagitis on the basis of the patient's significant cardiac history, her age, and low-flow state.
R. Obermeyer; K. Kasirajan; V. Erzurum; D. Chung
Separation of the single anterior foregut tube into the esophagus and trachea involves cell proliferation and differentiation, as well as dynamic changes in cell-cell adhesion and migration. These biological processes are regulated and coordinated at multiple levels through the interplay of the epithelium and mesenchyme. Genetic studies and in vitro modeling have shed light on relevant regulatory networks that include a number of transcription factors and signaling pathways. These signaling molecules exhibit unique expression patterns and play specific functions in their respective territories before the separation process occurs. Disruption of regulatory networks inevitably leads to defective separation and malformation of the trachea and esophagus and results in the formation of a relatively common birth defect, esophageal atresia with or without tracheoesophageal fistula (EA/TEF). Significantly, some of the signaling pathways and transcription factors involved in anterior foregut separation continue to play important roles in the morphogenesis of the individual organs. In this review, we will focus on new findings related to these different developmental processes and discuss them in the context of developmental disorders (or birth defects) commonly seen in clinics.
Jacobs, Ian J.; Ku, Wei-Yao; Que, Jianwen
We present two patients who developed delayed fistulization following esophageal replacement surgery. The first is a 13-year-old child who, at the age of 3 years, underwent a trans-mediastinal colonic esophageal replacement for a refractory corrosive injury followed by a retrosternal reverse gastric tube after an early catastrophic leak. Ten years later, he presented with a history of intermittent chest pain for 6 months. He developed a tension pneumo-pericardial tamponade caused by a fistula between gastric tube and pericardium. He recovered after sternotomy. The second was born prematurely with type C esophageal atresia and other malformations. After esophageal anastomosis, he developed a refractory stricture that was resected at 10 months. Despite a fundoplication at 4 years, the recurrent esophageal stricture required resection at 14 years, accomplished by mobilizing the stomach into the chest through a left thoracoabdominal incision. The postoperative course was complicated by a gastric leak in the chest with empyema, but the patient recovered and was able to eat. Five years later, he underwent an anterior spinal fusion to correct a worsening kyphoscoliosis. Postoperatively, he developed an ARDS picture, leakage of air through the gastrostomy, and a fatal pulmonary hemorrhage secondary to a gastro-bronchial fistula. Fistulization from esophageal replacement surgery represents a rare long-term complication that pediatric surgeons need to be aware of. PMID:19349000
Abdalwahab, Ahmed; Al Namshan, Mohammed; Al Rabeeah, Abdullah; Laberge, Jean-Martin
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.
Hanks, J.B.; Fisher, S.R.; Meyers, W.C.; Christian, K.C.; Postlethwait, R.W.; Jones, R.S.
Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development.1,2 Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations3 and necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and co-operates in induction of pluripotent stem cells.6,7,8 SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC.
Bass, Adam J.; Watanabe, Hideo; Mermel, Craig H.; Yu, Soyoung; Perner, Sven; Verhaak, Roel G.; Kim, So Young; Wardwell, Leslie; Tamayo, Pablo; Gat-Viks, Irit; Ramos, Alex H.; Woo, Michele S.; Weir, Barbara A.; Getz, Gad; Beroukhim, Rameen; O'Kelly, Michael; Dutt, Amit; Rozenblatt-Rosen, Orit; Dziunycz, Piotr; Komisarof, Justin; Chirieac, Lucian R.; LaFargue, Christopher J.; Scheble, Veit; Wilbertz, Theresia; Ma, Changqing; Rao, Shilpa; Nakagawa, Hiroshi; Stairs, Douglas B.; Lin, Lin; Giordano, Thomas J.; Wagner, Patrick; Minna, John D.; Gazdar, Adi F.; Zhu, Chang Qi; Brose, Marcia S.; Cecconello, Ivan; Ribeiro, Ulysses; Marie, Suely K.; Dahl, Olav; Shivdasani, Ramesh A.; Tsao, Ming-Sound; Rubin, Mark A.; Wong, Kwok K.; Regev, Aviv; Hahn, William C.; Beer, David G.; Rustgi, Anil K.; Meyerson, Matthew
The aberrant DNA methylation of tumor suppressor genes is well documented in esophageal cancer, including adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) as well as in Barrett's esophagus (BE), a pre-malignant condition that is associated with chronic acid reflux. BE is a well-recognized risk factor for the development of EAC, and consequently the standard of care is for individuals with BE to be placed in endoscopic surveillance programs aimed at detecting early histologic changes that associate with an increased risk of developing EAC. Yet because the absolute risk of EAC in individuals with BE is minimal, a clinical need in the management of BE is the identification of additional risk markers that will indicate individuals who are at a significant absolute risk of EAC so that they may be subjected to more intensive surveillance. The best currently available risk marker is the degree of dysplasia in endoscopic biopsies from the esophagus; however, this marker is suboptimal for a variety of reasons. To date, there are no molecular biomarkers that have been translated to widespread clinical practice. The search for biomarkers, including hypermethylated genes, for either the diagnosis of BE, EAC, or ESCC or for risk stratification for the development of EAC in those with BE is currently an area of active research. In this review, we summarize the status of identified candidate epigenetic biomarkers for BE, EAC, and ESCC. Most of these aberrantly methylated genes have been described in the context of early detection or diagnostic markers; others might prove useful for estimating prognosis or predicting response to treatment. Finally, special attention will be paid to some of the challenges that must be overcome in order to develop clinically useful esophageal cancer biomarkers. PMID:22406828
Kaz, Andrew M; Grady, William M
Background & Aims: Intraluminal pressure recording systems have not demonstrated predictable esophageal motor correlates of unexplained chest pain. This study used continuous high-frequency intraluminal ultrasonography to characterize esophageal contraction at the time of spontaneous and provoked chest pain. Methods: Intraluminal pressure, pH, and ultrasound images of the esophagus were recorded for a maximum of 24 hours in 10 subjects with
David H. Balaban; Yoshihiro Yamamoto; Jianmin Liu; Nonko Pehlivanov; Ralph Wisniewski; Dennis DeSilvey; Ravinder K. Mittal
We investigated progressive telomere shortening in normal human epidermis and lingual epithelium during aging, and attempted, in particular, to ascertain whether the telomere shortening that accompanies aging occurs at the same rate in different tissues. We studied telomeric DNA integrity, and estimated annual telomere loss, in 52 specimens of epidermis and 48 specimens of lingual epithelium collected at autopsy from subjects who had died at ages between 0 and 101 y. Most of the DNA samples were measured twice by southern blot hybridization. In addition, the correlation between telomere lengths in the two types of tissues was examined. The telomere reduction rates in epidermis and lingual epithelium were 36 bp and 30 bp per y, respectively, and these were significantly different. The rates obtained by the second measurements in epidermis and lingual epithelium were 39 and 32 bp per y, respectively, and these were also significantly different. The mean telomere lengths in the epidermis of eight neonates and the lingual epithelium of seven neonates were 13.2+/-1.0 and 13.8+/-1.0 kb, respectively. Comparison of telomere lengths in the two tissues for 41 paired samples showed that the mean telomere length in the epidermis (10.7+/-2.3 kb) was less than that in the lingual epithelium (12.4+/-2.5 kb); however, statistical analysis revealed a very significant relationship between epidermal and lingual epithelial telomere length (r=0.842, p<0.0001). These results indicate that the telomeres in epidermis and lingual epithelium are characterized by tissue-specific loss rates. PMID:12445186
Nakamura, Ken-Ichi; Izumiyama-Shimomura, Naotaka; Sawabe, Motoji; Arai, Tomio; Aoyagi, Yukitoshi; Fujiwara, Mutsunori; Tsuchiya, Eiju; Kobayashi, Yasuhito; Kato, Motonobu; Oshimura, Mitsuo; Sasajima, Koji; Nakachi, Kei; Takubo, Kaiyo
In normal airway epithelium, the cystic fibrosis transmembrane conductance regulator (CFTR) transports Cl(-) ions to the apical surface of the epithelium paralleled by the flow of water through transcellular and paracellular pathways. The hypothesis was tested whether CFTR not only regulates the transcellular but also the paracellular shunt pathway. Therefore, we performed measurements of transepithelial electrical resistance (TER) and paracellular (14)C-mannitol permeability in wtCFTR (16HBE14o(-)) and delF508-CFTR (CFBE41o(-)) expressing human bronchial epithelial cells. Under resting conditions, CFBE41o(-) cell monolayers exhibit a higher paracellular permeability and lower TER as compared to 16HBE14o(-) monolayers. Stimulation of CFTR by cAMP induces opposite effects in the two cell lines. 16HBE14o(-) monolayers show a sharp decrease of TER, in parallel with a concomitant increase of paracellular permeability. The change in paracellular permeability is mediated by a myosin II dependent mechanism because it can be blocked by the myosin light chain kinase inhibitor ML-7. In contrast, CFBE41o(-) cells respond to cAMP stimulation with a decrease of paracellular permeability, paralleled by slight increase of TER. We conclude that stimulation of wtCFTR increases vectorial transcellular salt transport and, simultaneously, the paracellular permeability allowing water to follow through the paracellular pathway. In contrast, in CF epithelium cAMP stimulation increases neither vectorial salt transport nor paracellular permeability which is likely to contribute to the CF pulmonary phenotype. Taken together, our results link CFTR dysfunction to an improper regulation of the paracellular transport route. PMID:21865736
Weiser, Nelly; Molenda, Natalia; Urbanova, Katarina; Bähler, Martin; Pieper, Uwe; Oberleithner, Hans; Schillers, Hermann
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.
Dabija-Wolter, G; Bakken, V; Cimpan, M R; Johannessen, A C; Costea, D E
Eosinophilic esophagitis (EoE) is a relatively new condition resulting in dysphagia or symptoms resembling gastroesophageal reflux disease, symptoms that also are common in patients with a history of esophageal atresia. We present 2 patients with persistent dysphagia after repair of esophageal atresia that was caused by EoE. Although the exact etiology and pathogenesis of EoE remain unclear, it is now generally accepted that it is the result of a T-helper cell 2-type immune response with a crucial role for the eosinophil-specific chemotaxis factor eotaxin 3 and eosinophils. Because there are genetic similarities between esophageal atresia and EoE, we speculate that patients with esophageal atresia are at increased risk for developing EoE. PMID:22703825
Gorter, Ramon R; Heij, Hugo A; van der Voorn, J Patrick; Kneepkens, C M Frank
MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2?-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.
Jin, Zhe; Cheng, Yulan; Gao, Yan; Feng, Xianling; Dong, Ming; Cao, Ziyi; Chen, Si; Yu, Huimin; Zhao, Zhenfu; Zhang, Xiaojing; Liu, Jie; Mori, Yuriko; Fan, Xinmin; Meltzer, Stephen J.
Senescence of human cells has largely been studied as an in vitro phenomenon resulting from replicative exhaustion. The literature contains many studies of retinal pigment epithelium (RPE) cells which document replicative senescence. Sev- eral studies by Burke and others illustrate the relationship between donor age and replicative lifespan, the relationship between geographical location of RPE in the posterior pole and
Leonard M. Hjelmeland; Vincent J. Cristofalo; Walter Funk; Elizabeth Rakoczy; Martin L. Katz
In the tortoise, Gopherus polyphemus, single unit spikes in the olfactory epithelium in response to amyl acetate were positive relative to the slow potential. The number of spikes in a response train was 4 to 15, the duration 3 to 4 msec, the height 0.5 to 2 mv. The height of successive spikes in a train decreased. The decrement in
Tatsuaki Shibuya; Sachiko Shibuya
The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids, carbon tetrachloride (CCl4) or alpha-naphthylisothiocyanate (ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium. These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts. Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies. PMID:16773709
Glaser, Shannon; Francis, Heather; Demorrow, Sharon; Lesage, Gene; Fava, Giammarco; Marzioni, Marco; Venter, Julie; Alpini, Gianfranco
The ingestion of food antigens plays an essential role in the development of eosinophilic esophagitis (EE) as total removal of dietary antigens by using an amino acid based oral formula improves clinical symptoms and esophageal histology in 98% of patient...
GERD, Barrett's Esophagus and the Risk for Esophageal Cancer Am I at Risk for Esophageal Cancer? There ... commonly in Caucasians as well as people with gastroesophageal reflux disease (GERD). This cancer is increasing in frequency. ...
This investigation used a high-frequency intraluminal ultrasound (HFIUS) probe to study changes in esophageal muscle thickness as a marker of muscle contraction. The aim of this study was to determine whether this technique could accurately measure distention of the esophagus during swallows of liquid bolus and during gastroesophageal reflux (GER) in normal subjects. Despite some limitations, HFIUS appears to be a valid technique for both of these measurements in normal subjects. Future studies in patients with symptomatic GER disease (GERD) should be able to determine whether typical symptoms such as heartburn, as well as atypical symptoms such as chest pain, are related to the GER-related distention of the esophagus. PMID:12928089
Mittal, Ravinder K
Background Study of the normal development of the intestinal epithelium has been hampered by a lack of suitable model systems, in particular ones that enable the introduction of exogenous genes. Production of such a system would advance our understanding of normal epithelial development and help to shed light on the pathogenesis of intestinal neoplasia. The criteria for a reliable culture system include the ability to perform real time observations and manipulations in vitro, the preparation of wholemounts for immunostaining and the potential for introducing genes. Results The new culture system involves growing mouse embryo intestinal explants on fibronectin-coated coverslips in basal Eagle's medium+20% fetal bovine serum. Initially the cultures maintain expression of the intestinal transcription factor Cdx2 together with columnar epithelial (cytokeratin 8) and mesenchymal (smooth muscle actin) markers. Over a few days of culture, differentiation markers appear characteristic of absorptive epithelium (sucrase-isomaltase), goblet cells (Periodic Acid Schiff positive), enteroendocrine cells (chromogranin A) and Paneth cells (lysozyme). Three different approaches were tested to express genes in the developing cultures: transfection, electroporation and adenoviral infection. All could introduce genes into the mesenchyme, but only to a small extent into the epithelium. However the efficiency of adenovirus infection can be greatly improved by a limited enzyme digestion, which makes accessible the lateral faces of cells bearing the Coxsackie and Adenovirus Receptor. This enables reliable delivery of genes into epithelial cells. Conclusion We describe a new in vitro culture system for the small intestine of the mouse embryo that recapitulates its normal development. The system both provides a model for studying normal development of the intestinal epithelium and also allows for the manipulation of gene expression. The explants can be cultured for up to two weeks, they form the full repertoire of intestinal epithelial cell types (enterocytes, goblet cells, Paneth cells and enteroendocrine cells) and the method for gene introduction into the epithelium is efficient and reliable.
Quinlan, Jonathan M; Yu, Wei-Yuan; Hornsey, Mark A; Tosh, David; Slack, Jonathan MW
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.
Stoner, Gary D. [Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210 (United States)], E-mail: email@example.com; Wang Lishu; Chen Tong [Division of Hematology and Oncology, Department of Internal Medicine, Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210 (United States)
We present a retrospective evaluation of our experience in the period that goes from January 1992 to December 1998, clinical records of 58 patients ages from 2 months old to 15 years, male and female, who were treated at the GI service of Instituto de Salud del Ni o, were reviewed. All of them had esophageal stenosis and were included in the Esophageal Dilatation Program with Savary-Gilliard bougies. The causes of Esophageal Stenosis in the study were: Caustic agents 37.9%, gastro esophageal reflux (GER) 20.7%, surgery sequela 19.0%, related to esophageal esclerotherapy 12.1%, foreign body itself or maneuvers to retrieve them 8.6%, stomach adenocarcinoma invading the esophagus. Patients were classified in three groups: Group 1: stenosis due to caustic agents Group 2: stenosis due to GER Group 3: The remaining causes mentioned above., In each the following was calculated: the arithmetical media, the range of dilatations sessions and the total number of them. The higher figures took place in group 1. So we conclude that the number of sessions is directly related with the cause of the stenosis, requiring more number of dilatations to get a better response. Finally the response to treatment is evaluated considering a good response in 72.4%. A mild response in 15.5% and therapeutic failure in 12.1% of patients. The rate of complications was 10.3 per patient and 1.1 in relation to the total number of dilatation sessions. The main complications were: gastric perforation, duodenal perforation, pneumomediastinum, esophago-tracheal fistulae andi pseudodiverticulum formation, with resolution as seen in posterior controls. These complications occured after the proceeding took place. The treatment was installed according to each case. The patients with duodenal perforation died. We conclude that esophageal dilatations in infants with esophageal stenosis, of different ethiology, are secure and efficient. PMID:12181577
Alarcón, Anibal; Talavera, Godofredo; Gonzales, Jóse; Rivera, Juan
The nasal epithelium of young adult white men in good health was evaluated by electron microscopy in a condition blind fashion relative to exposures of 2 ppm nitrogen dioxide (NO2) or clean air for 4 h. The exposure protocol involved two separate exposures of the same individuals to NO2 or clean air approximately 3 wk apart. We found qualitative and quantitative evidence that luminal border membranes of ciliated cells were ultrastructurally altered in six of seven samples of nasal epithelium obtained following NO2 exposures, although subsequent morphometric statistical analyses were not significant. This alteration was characterized by cilia containing excess matrix in which individual or, more commonly, multiple ciliary axonemes were embedded, and by vesiculations of luminal border ciliary membranes, a pattern less common in clean air-exposed control specimens. Although these patterns were not widespread, their morphology was consistent with findings of previous animal studies involving acute and chronic exposure to NO2. Our findings suggest that adverse effects on mucociliary function in normal humans due to acute exposure to low levels of NO2 are most likely minimal. However, in view of other reports of NO2 exposure in laboratory animals documenting ciliary injury, our observations support a view that similar patterns might appear more prominently with higher NO2 levels and/or more extended exposure intervals.
Carson, J.L.; Collier, A.M.; Hu, S.C.; Delvin, R.B. (Frank Porter Graham Child Development Center, Chapel Hill, NC (United States))
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. PMID:23082710
Monsanto, P; Almeida, N; Cipriano, M A; Gouveia, H; Sofia, C
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.
Zelenak, Kamil, E-mail: firstname.lastname@example.org [University Hospital, Department of Radiology (Slovakia); Mistuna, Dusan; Lucan, Jaroslav [University Hospital, Department of Surgery (Slovakia); Polacek, Hubert [University Hospital, Department of Radiology (Slovakia)
Proinflammatory factors, including neutrophil-derived oxygen free radicals and inflammatory cytokines, have recently been implicated in the pathogenesis of reflux esophagitis. Rebamipide has been widely used as an anti-ulcer agent. The aim of the present study was to assess the protective effect of rebamipide against acute reflux esophagitis in rats. Esophagitis was induced in rats by ligation at the limiting ridge
Kazuhiro Katada; Norimasa Yoshida; Yutaka Isozaki; Naoya Tomatsuri; Hiroshi Ichikawa; Yuji Naito; Takeshi Okanoue; Toshikazu Yoshikawa
Esophageal atresia is a common and serious developmental anomaly, of which the causes remain largely unknown. Studies in vertebrate models indicate the importance of the sonic hedgehog pathway in esophageal atresia, but its relevance to the human condition remains to be defined. Now, three genes have been identified that cause syndromic forms of esophageal atresia when mutated. NMYC and SOX2
Han G Brunner; Hans van Bokhoven
Esophageal carcinosarcoma is a rare malignant tumor composing of both carcinomatous and sarcomatous elements. Endoscopic therapy is less invasive and may represent an alternative to esophagectomy for superficial esophageal carcinosarcoma. Here, we report a 61-year-old male who was diagnosed as esophageal carcinosarcoma and underwent endoscopic polypectomy with well tolerance and favorable prognosis. We also present a brief review of the
Feng Ji; Yue-Mei Xu; Cheng-Fu Xu
Objective: Chronic esophageal foreign bodies (CEFB) are associated with a high incidence of morbidity and mortality in adults. However, the presentation, management and outcome of chronic esophageal foreign bodies in children are not well described. Methods: We performed a retrospective chart review of children with chronic esophageal foreign bodies admitted to the Children’s Hospital Medical Center, Cincinnati, OH, between May
Robert Sean Miller; J. Paul Willging; Michael J. Rutter; Korpong Rookkapan
Immunohistochemical techniques were used to investigate the epithelial expression of VLA-1 in inflammatory bowel disease in six patients with Crohn's disease, in four patients with ulcerative colitis, and in one patient with indeterminate colitis, and compared with that in the small intestine and colons of 10 normal controls. In normal small bowel VLA-1 was expressed on crypt epithelial cells and only weakly or not at all on surface epithelium. VLA-1 was again expressed weakly in normal colon, except in one case, a 1 year old child with diarrhoea but no histological abnormalities. In small and large intestine affected with Crohn's disease, ulcerative colitis, or indeterminate colitis, there was increased expression of VLA-1 on the basolateral aspects of crypt cells and de novo expression on surface epithelium. It is suggested that this is an adaptive response to prevent epithelial cell loss as a result of inflammation in the underlying lamina propria. Images
MacDonald, T T; Horton, M A; Choy, M Y; Richman, P I
Patients with esophageal cancer have a poor prognosis because they often have no symptoms until their disease is advanced. There are no screening recommendations for patients unless they have Barrett’s esophagitis or a significant family history of this disease. Often, esophageal cancer is not diagnosed until patients present with dysphagia, odynophagia, anemia or weight loss. When symptoms occur, the stage is often stage III or greater. Treatment of patients with very early stage disease is fairly straight forward using only local treatment with surgical resection or endoscopic mucosal resection. The treatment of patients who have locally advanced esophageal cancer is more complex and controversial. Despite multiple trials, treatment recommendations are still unclear due to conflicting data. Sadly, much of our data is difficult to interpret due to many of the trials done have included very heterogeneous groups of patients both histologically as well as anatomically. Additionally, studies have been underpowered or stopped early due to poor accrual. In the United States, concurrent chemoradiotherapy prior to surgical resection has been accepted by many as standard of care in the locally advanced patient. Patients who have metastatic disease are treated palliatively. The aim of this article is to describe the multidisciplinary approach used by an established team at a single high volume center for esophageal cancer, and to review the literature which guides our treatment recommendations.
Villaflor, Victoria M; Allaix, Marco E; Minsky, Bruce; Herbella, Fernando A; Patti, Marco G
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
Khayyat, Yasir Mohammed
Traditionally, open repair of esophageal atresia (EA) with tracheoesophageal fistula (TEF) required thoracotomy. Innovations in minimal access surgery have created a thoracoscopic technique resulting in violation of the pleural space. Most pediatric surgeons favor an extrapleural approach for open repair. We present a novel minimal access, extrapleural technique for repairing EA with TEF. A 2-day-old infant with EA and distal TEF underwent thoracoscopic extrapleural repair that utilized three ports. Initial creation of the extrapleural space was achieved through one of the port sites and was completed thoracoscopically. A thoracoscopic repair of EA with distal TEF was achieved within the extrapleural space. A small tear in the pleura was inadvertently created during the dissection. The child began feeding normally. At 1 year of age, the patient had dysphagia requiring a single esophageal dilatation. This is the first known report of an extrapleural thoracoscopic repair of EA with TEF. Although thoracoscopic repairs of EA/TEF have been previously reported, these were all done transpleurally. Many pediatric surgeons favor the extrapleural approach for two reasons: (1) containment of a potential leak within the extrapleural space, avoiding an empyema, and (2) easier transpleural access for future thoracic procedures. PMID:15789240
Tsao, Kuojen; Lee, Hanmin
Background Most inoperable patients with esophageal-advanced cancer (EGC) have a poor prognosis. Esophageal stenting, as part of a palliative therapy management has dramatically improved the quality of live of EGC patients. Airway stenting is generally proposed in case of esophageal stent complication, with a high failure rate. The study was conducted to assess the efficacy and safety of scheduled and non-scheduled airway stenting in case of indicated esophageal stenting for EGC. Methods and Findings The study is an observational study conducted in pulmonary and gastroenterology endoscopy units. Consecutive patients with EGC were referred to endoscopy units. We analyzed the outcome of airway stenting in patients with esophageal stent indication admitted in emergency or with a scheduled intervention. Forty-four patients (58±\\?8 years of age) with esophageal stenting indication were investigated. Seven patients (group 1) were admitted in emergency due to esophageal stent complication in the airway (4 fistulas, 3 cases with malignant infiltration and compression). Airway stenting failed for 5 patients. Thirty-seven remaining patients had a scheduled stenting procedure (group 2): stent was inserted for 13 patients with tracheal or bronchial malignant infiltration, 12 patients with fistulas, and 12 patients with airway extrinsic compression (preventive indication). Stenting the airway was well tolerated. Life-threatening complications were related to group 1. Overall mean survival was 26+/?10 weeks and was significantly shorter in group 1 (6+/?7.6 weeks) than in group 2 (28+/?11 weeks), p<0.001). Scheduled double stenting significantly improved symptoms (95% at day 7) with a low complication rate (13%), and achieved a specific cancer treatment (84%) in most cases. Conclusion Stenting the airway should always be considered in case of esophageal stent indication. A multidisciplinary approach with initial airway evaluation improved prognosis and decreased airways complications related to esophageal stent. Emergency procedures were rarely efficient in our experience.
Paganin, Fabrice; Schouler, Laurent; Cuissard, Laurent; Noel, Jean Baptiste; Becquart, Jean-Philippe; Besnard, Mathieu; Verdier, Laurent; Rousseau, Denis; Arvin-Berod, Claude; Bourdin, Arnaud
Patients who have undergone repair of esophageal atresia and tracehoesophageal fistula as infants have been noted to have residual esophageal dysmotility and pulmonary dysfunction during their childhood years. However, limited information is available about the long-term follow-up of these patients. In this study we performed esophageal and pulmonary function studies on 12 adults who had required surgical repair of these
Jeffrey A. Biller; Julian L. Allen; Samuel R. Schuster; S. T. Treves; Harland S. Winter
Answer questions and earn CME/CNE Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge. CA Cancer J Clin 2013. © 2013 American Cancer Society. PMID:23584949
Lagergren, Jesper; Lagergren, Pernilla
Answer questions and earn CME/CNE Esophageal adenocarcinoma (EAC) is characterized by 6 striking features: increasing incidence, male predominance, lack of preventive measures, opportunities for early detection, demanding surgical therapy and care, and poor prognosis. Reasons for its rapidly increasing incidence include the rising prevalence of gastroesophageal reflux and obesity, combined with the decreasing prevalence of Helicobacter pylori infection. The strong male predominance remains unexplained, but hormonal influence might play an important role. Future prevention might include the treatment of reflux or obesity or chemoprevention with nonsteroidal antiinflammatory drugs or statins, but no evidence-based preventive measures are currently available. Likely future developments include endoscopic screening of better defined high-risk groups for EAC. Individuals with Barrett esophagus might benefit from surveillance, at least those with dysplasia, but screening and surveillance strategies need careful evaluation to be feasible and cost-effective. The surgery for EAC is more extensive than virtually any other standard procedure, and postoperative survival, health-related quality of life, and nutrition need to be improved (eg, by improved treatment, better decision-making, and more individually tailored follow-up). Promising clinical developments include increased survival after preoperative chemoradiotherapy, the potentially reduced impact on health-related quality of life after minimally invasive surgery, and the new endoscopic therapies for dysplastic Barrett esophagus or early EAC. The overall survival rates are improving slightly, but poor prognosis remains a challenge. PMID:23818335
Lagergren, Jesper; Lagergren, Pernilla
It is unclear whether there is any difference in esophageal motor abnormalities between patients complaining of dysphagia for solids or both solids and liquids. The aim of this study was to determine any difference in the manometric findings between patients with dysphagia for solids and those with mixed dysphagia. Manometric tracings were performed in 200 consecutive patients (66 M, 134 F; mean age = 51 years) with nonobstructive dysphagia. Ambulatory pH studies were performed in all patients. Subjects were divided into two groups: patients with solid dysphagia (n = 94, 33 M, 61 F; mean age = 51 years) and those with mixed dysphagia (n = 106, 33 M, 73 F; mean age = 51 years). A normal motility study was the most frequent finding. Achalasia occurred more frequently in patients with mixed dysphagia than in those with solid dysphagia (12% vs. 3%, p < 0.01). Gastroesophageal reflux disease (GERD) was observed in 59% of patients with solid dysphagia compared with 29% of patients with mixed dysphagia (p < 0.02). The most common esophageal motility abnormality is nonspecific esophageal motility disorders. This study has shown that abnormal esophageal motility occurs slightly more in mixed dysphagia than solid dysphagia. The clinical utility of a symptomatic differentiation of patients with solid or mixed dysphagia appears to be limited. PMID:16633869
Chen, Chien-Lin; Orr, William C
Esophageal hiatal hernia was diagnosed in 11 young Chinese Shar-Pei dogs between October 1985 and July 1991. The dogs ranged in age from 2 to 11 months and included 3 females and 8 males. The most common clinical signs were regurgitation, vomiting, and hypersalivation. Physical examination was normal in 6 dogs; abnormal physical examination findings in the other 5 dogs included fever, dehydration, hypersalivation, and pulmonary wheezes and crackles. Laboratory evaluation was significant only for neutrophilia in 5 dogs. A diagnosis of hiatal hernia was made on the basis of survey thoracic radiographic and/or barium esophagram findings of displacement of the esophagogastric junction and stomach into the thoracic cavity; the diagnosis was confirmed by surgery in 9 dogs and at necropsy in 2 dogs. Megaesophagus (n = 7), gastroesophageal reflux (n = 4), and esophageal hypomotility (n = 1) were additional findings in some dogs. Aspiration pneumonia was diagnosed in 7 of the dogs. Medical therapies formulated for the therapy of presumed reflux esophagitis generally failed to resolve the clinical signs associated with the hiatal hernia. Hiatal herniae were surgically repaired in 9 of the Shar-Peis by various combinations of diaphragmatic crural apposition, fixation of the esophagus to the diaphragmatic crus (esophagopexy), and left fundic tube gastropexy. Eight of the animals survived surgery, six of which have been asymptomatic since surgery (19 to 36 months). The megaesophagus, esophageal hypomotility, and bronchopneumonia resolved in all of these dogs. PMID:8246209
Callan, M B; Washabau, R J; Saunders, H M; Kerr, L; Prymak, C; Holt, D
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.
Spencer, A.J.; Roomans, G.M. (Univ. of Uppsala (Sweden))
Simple and robust method for identifying the retinal pigment epithelium (RPE) from optical coherence tomography images is demonstrated. At first, the maximum intensity value of each A-scans were determined and the depth position of those pixels are identified. The obtained 2D matrix is used as first estimation for the position of RPE. The erroneous pixel from the RPE is masked out and new approximation for them is calculated based on the neighbouring pixels. Finally, the obtained RPE matrix is smoothened. The RPE identification is used for separating the retina and choroid from optical coherence tomography images obtained by 830 nm spectral domain OCT. Both normal and ARMD patient eye were investigated to demonstrate the usability of that method. The calculation time for three dimensional data set (1024x450x137 pixels) was only 16 seconds and it identifies RPE reliably.
Fabritius, Tapio; Makita, Shuichi; Myllylä, Risto; Yasuno, Yoshiaki
With the goal to assess the efficacy of a simple set of endoscopic ligation of esophageal varices, we conducted a prospective study in the public Goyeneche Hospital, Arequipa, Per . Ten patients between 17 and 68 years old (mean 48 years)diagnosed with digestive hemorrhage due to grade III-IV esophageal varices caused by hepatic cirrhosis were subject to endoscopic ligation. We succesfully used this simple device without overtube, in a total of 34 sessions, with 3 to 6 bands (mean 4) per session in only one introduction of endoscopy without active vericeal hemorrhage. Endoscopic treatment was repeated at 1-to-2 week intervals until variceal eradication was achieved. Only one complication (p<0.001) in the third session due to esophageal distal estenosis that was resolved with dilatation. This procedure could be useful as practical alternative of easy access and lower cost as a therapeutic option to sclerotheraphy and less complications. PMID:12138386
Five patients with early esophageal carcinoma were treated by 6-12 Gy of intracavitary irradiation following 50-60 Gy of external irradiation as a boost therapy. Surgery was not performed in these cases. None of the patients had local recurrence after radiation therapy, as demonstrated by esophagography and endoscopy. Three patients have been alive for 1-3 years 10 months. Esophageal ulceration induced by intracavitary irradiation has occurred in three of the five patients; however, intracavitary irradiation is still a beneficial treatment because of its efficacy in controlling local lesions and because radiation ulceration can eventually be cured. Intracavitary irradiation is recommended to follow external irradiation as a boost therapy for the treatment of early esophageal carcinoma.
Hishikawa, Y.; Tanaka, S.; Miura, T.
MicroRNAs (miRs) have recently emerged as a novel class of gene expression regulators. The number of studies documenting an altered miR expression pattern in cancer continues to expand rapidly. Critical information is continuously gained regarding how aberrantly expressed miRs contribute to carcinogenesis. Current studies provide evidence that analyses of miR expression patterns have potential clinical applications toward developing tumor biomarkers to identify the presence and dissemination of esophageal cancer, as well as to assess tumor chemo- or radiosensitivity. The incidence of esophageal cancer is on the rise, and this disease continues to portend a poor prognosis. The current review addresses ways in which altered miR expression contributes to esophageal carcinogenesis, along with how recent discoveries may be applied clinically.
David, Stefan; Meltzer, Stephen J.
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.
Liu, Qingjun; Hu, Ning; Ye, Weiwei; Zhang, Fenni; Wang, Hua; Wang, Ping
The Objective is to identify candidate biomarkers for Squamous cell carcinoma (ESCC) in three ethnics in Xinjiang as well\\u000a as reveal molecular mechanism. Proteins from 15 pairs of ESCC and matching adjacent normal esophageal tissues (five pairs\\u000a in each ethnic of Kazakh, Uygur and Han) were separated by 2-DE and differentially proteins were identified by matrix-assisted\\u000a laser desorption\\/ionization time-of-flight MS.
Zan Liu; Jun-guo Feng; Aerziguli Tuersun; Tao Liu; Hui Liu; Qing Liu; Shu-tao Zheng; Cong-gai Huang; Guo-dong Lv; Ilyar Sheyhidin; Xiao-mei Lu
Summary A culture system utilizing rat esophageal epithelial cells has been developed. Four normal and eightN-nitrosobenzylmethylamine-treated lines were compared with respect to chromosome number, anchorage-independent growth in agarose,\\u000a and tumorigenic potential in syngenic rats. All cell lines were aneuploid with nine in the near-tetraploid range and three\\u000a in the near-diploid range. No relation between tumorigenic potential and chromosome number or structure
Gary D. Stoner; Merrill S. Babcock; Maureen M. Mc Corquodale; William T. Gunning; Roubadeh Jamasbi; Neilma Budd; Bharati Hukku
Background Treatment failure for esophageal carcinoma is frequently due to lymph node metastasis and invasion to neighboring organs. The aim of the present study was to investigate invasion- and metastasis-related genes in esophageal carcinoma cells in vitro and in vivo. Methods A metastasis model using a Matrigel invasion clonal selection approach was employed to establish a highly invasive subline EC9706-P4 from the esophageal carcinoma cell (ESCC) line EC9706. The differentially expressed genes of the subline and the parental cells determined by gene microarrays were further analyzed by RT-PCR and Western blotting. Results We identified sphingosine kinase 1 (SPHK1) as an invasion and metastasis-related gene of esophageal cancer. SPHK1 was overexpressed in the EC9706-P4 subline with high invasive capacity. Among six ESCC lines tested, KYSE2 and KYSE30 cells showed the highest SPHK1 mRNA and protein expressions as well as the most invasive phenotype. By Western blotting, in 7/12 cases (58%), SPHK1 expression was higher in esophageal carcinomas than in the companion normal tissue. In 23/30 cases (76%), SPHK1 protein expression was upregulated in the tumors compared to matched normal tissue by immunohistochemistry (IHC). Esophageal carcinoma tissue microarray analysis indicated that SPHK1 expression correlated with the depth of tumor invasion (P < 0.0001) and lymph node metastasis (P = 0.016). By Kaplan-Meier analysis, strong SPHK1 expression was significantly associated with clinical failure (P < 0.01), suggesting the involvement of SPHK1 in aggressiveness of human esophageal carcinoma. SPHK1 overexpression significantly increased the invasiveness of EC9706 cells in vitro and also increased EC9706 cell growth and spontaneous metastasis in vivo, promoting significant increases in tumor growth, tumor burden and spontaneous lung metastasis in nude mice. SPHK1 expression significantly correlated with the expression of many EGFR pathway genes associated with invasion of cancer cells. SPHK1 protein expression also significantly correlated with the phosphorylation of EGFR. Conclusion In summary, our data implicate SPHK1 in the metastasis of esophageal cancer. Our study also identified downstream mediators of SPHK1 in esophageal cancer cells that may mediate enhanced malignant behavior, and several of these mediators may be useful as therapeutic targets.
We evaluated the clinical utility of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)–positron emission tomography (PET)\\/computed tomography (CT) on the precise localization of pathologic foci\\u000a and exclusion of normal variants in the imaging evaluation of patients with esophageal carcinoma. Combined PET\\/CT scans were\\u000a performed in 60 patients (50 males, 10 females, age range 47–84 years) with history of esophageal carcinoma either at the\\u000a time of initial
Hossein Jadvar; Robert W. Henderson; Peter S. Conti
Modern handling of esophageal cancer patients is based on a multidisciplinary concept, but surgery remains the primary curative treatment modality. Improvements in the perioperative care have reduced the overall morbidity and mortality, but 2-7% of the patients may still die within 30 days as a direct consequence of complications related to the esophagectomy procedure. Primarily based on results from randomized studies published after 2000 this review describes some of the factors that may contribute to the development of postoperative complications following esophageal cancer surgery as well as studies intended to finding ways of reducing the complication rate. PMID:24019042
Bau Mortensen, M
Use of 3H-thymidine autoradiography and unilateral vomeronasal (VN) axotomy has permitted us to demonstrate directly the existence of VN stem cells in the adult garter snake and to trace continuous bipolar neuron development and migration in the normal VN and deafferentated VN epithelium in the same animal. The vomeronasal epithelium and olfactory epithelium of adult garter snakes are both capable of incorporating 3H-thymidine. In the sensory epithelium of the vomeronasal organ, 3H-thymidine-labeled cells were initially restricted to the base of the undifferentiated cell layer in animals surviving 1 day following 3H-thymidine injection. With increasing survival time, labeled cells progressively migrated vertically within the receptor cell column toward the apex of the bipolar neuron layer. In both the normal and denervated VN epithelium, labeled cells were observed through the 56 days of postoperative survival. In the normal epithelium, labeled cells were always located within the matrix of the intact receptor cell columns. However, labeled cells of the denervated epithelium were always located at the apical front of the newly formed cell mass following depletion of the original neuronal cell population. In addition, at postoperative days 28 and 56, labeled cells of the denervated VN epithelium achieved neuronal differentiation and maturation by migrating much farther away from the base of the receptor cell column than the labeled cells on the normal, unoperated contralateral side. This study directly demonstrates that basal cells initially incorporating 3H-thymidine are indeed stem cells of the VN epithelium in adult garter snakes.
Wang, R.T.; Halpern, M.
Drug-induced esophageal injury is an under-recognized clinical problem, and is associated with antibiotic use in more than 50% of cases. The current report describes a teenage girl who presented with symptoms of pill-induced esophagitis following doxycycline use. Subsequent investigations identified a previously undiagnosed vascular ring. Although most patients who experience drug-induced esophageal injury have no underlying anatomical or functional disorder of the esophagus, the condition is more common in areas of esophageal narrowing. The present case illustrates the possibility of an occult esophageal obstruction representing a risk factor for pill esophagitis. The etiologies, mechanisms and management of drug-induced esophageal injury are reviewed, and aspects of vascular rings that are relevant to paediatricians are discussed.
Guttman, Orlee R; Zachos, Mary
Introduction: Even after complete tumor removal by surgery, the clinical outcomes remain poor in patients with advanced esophageal cancer, justifying the need for new treatment options. Epidermal growth factor receptor (EGFR) is a molecular target for antibody-based therapy in various cancer types, and it may play important roles in the development of esophageal cancer. Areas covered: This review evaluates the expression, function, and mechanism of EGFR in esophageal cancer and analyzes its value for the prognosis and therapy of esophageal cancer. Future developments toward the clinical applications of EGFR to cancer treatment are also envisaged. Expert opinion: EGFR may function as an ideal therapeutic target for esophageal cancer. Further investigation of epidermal growth-factor-receptor-mediated pathways will push insight into the novel strategies of target therapy for esophageal cancer. More clinical trials should be performed to promote the success of therapeutic-clinical use of EGFR and its targets in esophageal cancer. PMID:23855932
Hong, Liu; Han, Yu; Brain, Lubi
Background: The tight junction plays a crucial role in structural esophageal epithelial defenses that maintain esophageal epithelial integrity. We examined the roles of ZO-1 and epidermal growth factor (EGF) in esophageal epithelial defense against acid using human esophageal epithelial cells. Methods: Human esophageal epithelial cells (TE-1) were incubated with acidified medium in the presence or absence of various doses of
Masatsugu Okuyama; Yasuhiro Fujiwara; Tetsuya Tanigawa; Kenji Watanabe; Masatsugu Shiba; Kazunari Tominaga; Toshio Watanabe; Nobuhide Oshitani; Kazuhide Higuchi; Tetsuo Arakawa
Objective To document what can be accomplished with surgical resection done according to the classical principles of surgical oncology. Methods One hundred consecutive patients underwent en bloc esophagectomy for esophageal adenocarcinoma. No patient received pre- or postoperative chemotherapy or radiation therapy. Tumor depth and number and location of involved lymph nodes were recorded. A lymph node ratio was calculated by dividing the number of involved nodes by the total number removed. Follow-up was complete in all patients. The median follow-up of surviving patients was 40 months, with 23 patients surviving 5 years or more. Results The overall actuarial survival rate at 5 years was 52%. Survival rates by American Joint Commission on Cancer (AJCC) stage were stage 1 (n = 26), 94%; stage 2a (n = 11), 65%; stage 2b (n = 13), 65%; stage 3 (n = 32), 23%; and stage 4 (n = 18), 27%. Sixteen tumors were confined to the mucosa, 16 to the submucosa, and 13 to the muscularis propria, and 55 were transmural. Tumor depth and the number and ratio of involved nodes were predictors of survival. Metastases to celiac (n = 16) or other distant node sites (n = 26) were not associated with decreased survival. Local recurrence was seen in only one patient. Latent nodal recurrence outside the surgical field occurred in 9 patients and systemic metastases in 31. Tumor depth, the number of involved nodes, and the lymph node ratio were important predictors of systemic recurrence. The surgical death rate was 6%. Conclusion Long-term survival from adenocarcinoma of the esophagus can be achieved in more than half the patients who undergo en bloc resection. One third of patients with lymph node involvement survived 5 years. Local control is excellent after en bloc resection. The extent of disease associated with tumors confined to the mucosa and submucosa provides justification for more limited and less morbid resections.
Hagen, Jeffrey A.; DeMeester, Steven R.; Peters, Jeffrey H.; Chandrasoma, Para; DeMeester, Tom R.
Background: Barrett's esophagus (BE) affects up to 12 million Americans and confers an increased risk for development of esophageal adenocarcinoma (EAC). EAC is often fatal unless detected early. Given the high prevalence, high cost of surveillance and relatively low risk of most affected individuals, identification of high-risk patients for additional scrutiny, regular surveillance, or ablative therapy is crucial. The exploration of “field effect” by probing uninvolved esophageal mucosa to predict the risk of EAC has the potential as an improved surveillance and prevention strategy. In this study, we evaluate the ability of nuclear nano-architecture markers from normal squamous esophagus and gastric cardia to detect the “field effect” of esophageal dysplasia and EAC, and their response to endoscopic therapy. Methods: Patients with normal esophagus, gastroesophageal reflux, BE and EAC were eligible for enrollment. We performed endoscopic cytology brushings of the gastric cardia, ~1-2 cm below the gastroesophageal junction, and of the normal squamous esophageal mucosa at ~20 cm from the incisors and standard cytology slides were made using Thinprep method. Optical analysis was performed on the cell nuclei of cytologically normal-appearing epithelial cells. Results: The study cohort consisted of 128 patients. The nuclear nano-architecture markers detected the presence of esophageal dysplasia and EAC with statistical significance. The field effect does not exhibit a spatial dependence. These markers reverted toward normal in response to endoscopic therapy. Conclusions: Optical analysis of gastric cardia and upper squamous esophagus represents a potentially viable method to improve risk stratification and ease of surveillance of patients with Barrett's esophagus and to monitor the efficacy of ablative therapy.
Fasanella, Kenneth E.; Bista, Rajan K.; Staton, Kevin; Rizvi, Sumera; Uttam, Shikhar; Zhao, Chengquan; Sepulveda, Antonia; Brand, Randall E.; McGrath, Kevin; Liu, Yang
Introduction: Lymphatic dissemination of a (non-cervical) esophageal tumor to the neck is generally considered as distant metastasis. The aim of this study was to determine the additional value of external ultrasonography (US) to detect lymphatic metastasis to the neck after normal CT scan (CT) with or without normal PET scan (PET). Methods: Between January 2003 and December 2005, 306 patients
J. M. T. Omloo; M. van Heijl; N. J. Smits; S. S. K. S. Phoa; M. I. van Berge Henegouwen; G. W. Sloof; J. J. B. van Lanschot
The intestinal epithelium is constantly exposed to inducers of reactive oxygen species (ROS) such as commensal microorganisms. Levels of ROS are normally maintained at non-toxic levels, but dysregulation of ROS is involved in intestinal inflammatory diseases. Here we report that TGF?-activated kinase 1 (TAK1) is a key regulator of ROS in the intestinal epithelium. tak1 gene deletion in the mouse intestinal epithelium caused tissue damage involving enterocyte apoptosis, disruption of tight junctions and inflammation. Disruption of TNF signaling, which is a major intestinal damage inducer, rescued the inflammatory conditions but not apoptosis or disruption of tight junctions in the TAK1-deficient intestinal epithelium, suggesting that TNF is not a primary inducer of the damage noted in TAK1-deficient intestinal epithelium. We found that TAK1 deficiency resulted in reduced expression of several antioxidant responsive genes and reduced the protein level of a key antioxidant transcription factor NF-E2-related factor 2 (Nrf2), which resulted in accumulation of ROS. Exogenous antioxidant treatment could reduce apoptosis and disruption of tight junctions in the TAK1-deficient intestinal epithelium. Thus, TAK1 signaling regulates ROS through Nrf2, which is important for intestinal epithelial integrity.
Kajino-Sakamoto, Rie; Omori, Emily; Nighot, Prashant K.; Blikslager, Anthony T.; Matsumoto, Kunihiro; Ninomiya-Tsuji, Jun
Esophageal obstruction from any cause is debilitating. In patients with malignant obstruction palliation to relieve pain and dysphagia is the primary goal. Conventional endoluminal prostheses allow variable palliation. Covered expandable metallic stents with an 18-mm lumen allow improved deglutition. From December 1994 through December 1998, 59 patients underwent placement of self-expanding silicone-covered esophageal stents for esophageal obstruction. There were 36 men and 23 women ranging in age from 41 to 94. All patients underwent esophageal dilation using a flexible gastroscope and Savary bougies. After dilation placement of the stent was performed under fluoroscopic control. Follow-up was complete in all patients. Technical success was achieved in all patients. There was one postoperative death (bronchopulmonary fistula), one migration of the stent requiring removal, and one recurrent obstruction. The remaining stents were well tolerated even in the cervical region (four patients). All patients returned to a diet of solid foods. We conclude that covered self-expanding esophageal metallic stents are technically simple and safe to insert and appear to provide durable excellent palliation of esophageal obstruction due to either benign or malignant conditions. PMID:11261624
Cordero, J A; Moores, D W
Background We attempted to identify novel biomarkers and therapeutic targets for esophageal squamous cell carcinoma by gene expression profiling of frozen esophageal squamous carcinoma specimens and examined the functional relevance of a newly discovered marker gene, WDR66. Methods Laser capture microdissection technique was applied to collect the cells from well-defined tumor areas in collaboration with an experienced pathologist. Whole human gene expression profiling of frozen esophageal squamous carcinoma specimens (n?=?10) and normal esophageal squamous tissue (n?=?18) was performed using microarray technology. A gene encoding WDR66, WD repeat-containing protein 66 was significantly highly expressed in esophageal squamous carcinoma specimens. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in a second and independent cohort (n?=?71) consisting of esophageal squamous cell carcinoma (n?=?25), normal esophagus (n?=?11), esophageal adenocarcinoma (n?=?13), gastric adenocarcinoma (n?=?15) and colorectal cancers (n?=?7). In order to understand WDR66’s functional relevance siRNA-mediated knockdown was performed in a human esophageal squamous cell carcinoma cell line, KYSE520 and the effects of this treatment were then checked by another microarray analysis. Results High WDR66 expression was significantly associated with poor overall survival (P?=?0.031) of patients suffering from esophageal squamous carcinomas. Multivariate Cox regression analysis revealed that WDR66 expression remained an independent prognostic factor (P?=?0.042). WDR66 knockdown by RNA interference resulted particularly in changes of the expression of membrane components. Expression of vimentin was down regulated in WDR66 knockdown cells while that of the tight junction protein occludin was markedly up regulated. Furthermore, siRNA-mediated knockdown of WDR66 resulted in suppression of cell growth and reduced cell motility. Conclusions WDR66 might be a useful biomarker for risk stratification of esophageal squamous carcinomas. WDR66 expression is likely to play an important role in esophageal squamous cell carcinoma growth and invasion as a positive modulator of epithelial-mesenchymal transition. Furthermore, due to its high expression and possible functional relevance, WDR66 might be a novel drug target for the treatment of squamous carcinoma.
Spontaneous esophageal rupture is an uncommon and poorly understood condition. Recurrent rupture is extremely rare, with only one previously reported case in the literature. Here, we present a case series of two patients who had recurrent ruptures, and discuss the principles underlying the management of such cases. Q 2005 Elsevier B.V. All rights reserved.
Omar A. Khan; Clifford W. Barlow; David F. Weeden; Khalid M. Amer
Auscultation of heart sound and breathing sound in anesthesia is very important, because it can provide the information of patient's cardiorespiratory system. In operating room, anesthesiologists use esophageal stethoscope, which is a device to measure heart sound or respiratory sound by inserting a catheter into the esophagus close to heart. It is not only low cost and very simple to
Ji-Yun Shin; Young Cheol Kim; Seung Woon Lim; Eun Jong Cha; Tae Soo Lee
No Heading The esophagus as a site for drug delivery has been much overlooked in comparison to the remainder of the gastrointestinal tract. The low permeability and transient nature of the esophagus means that it is unsuitable for delivery of drugs for systemic action. However, esophageal disorders including fungal infection, cancers, motility dysfunction, and damage due to gastric reflux may
INTRODUCTION Bezoar in the esophagus is a rare condition and associated with structural or functional abnormalities of the esophagus. Endoscopy is the main tool for diagnosis and treatment for bezoar in the esophagus. PRESENTATION OF CASE Here we present a case where an endoscopic evacuation of an esophageal bezoar was unsuccessful. We treated the bezoar through a nasogastric tube using a cocktail composed of pancreatic enzymes dissolved in Coca-Cola. DISCUSSION Endoscopy is regarded as the mainstay for the diagnosis and treatment of esophageal bezoars. However, when this approach fails, other treatment options include dissolution therapy, and surgical exploration and removal of the bezoar. Surgical removal of an esophageal bezoar is associated with a high risk of morbidity and mortality. We advocate that dissolving therapy should be the first choice of treatment when endoscopic evacuation is not possible. CONCLUSION This is the first report describing a successful treatment of an esophageal bezoar with a cocktail of Coca-Cola and pancreatic enzymes. It is an effective, inexpensive, and worldwide available treatment and should be considered when endoscopic evacuation fails.
Yaqub, Sheraz; Shafique, Muhammad; Kjaestad, Erik; Thorsen, Yngve; Lie, Erik S.; Dahl, Vegard; Bakka, Njal; R?kke, Ola
The authors report a series of eight cases of isolated tracheoesophageal fistula without esophageal atresia (or an H type fistula), treated in three pediatric ENT departments. This is a rare malformation whose diagnosis requires investigation for associated anomalies. The clinical signs are mainly respiratory but also digestive and the symptomatology can be severe. The diagnosis can be made with a
Erwan Genty; Pierre Attal; Richard Nicollas; Gilles Roger; Jean-Michel Triglia; Erea-Noël Garabedian; Serge Bobin
We report a newborn with esophageal atresia (EA) in whom right tracheal bronchus (TB) and a tracheal diverticulum were identified intra-operatively. The right TB was further confirmed on MRI scan performed post-operatively. Such a tracheal trifurcation associated with EA has not been reported hitherto from Indian subcontinent.
Background/Aim: Thrombocytosis is found to be associated with unfavorable prognosis in esophageal carcinoma. Platelets produce thymidine phosphorylase which is a platelet-derived endothelial cell growth factor with angiogenic activity. Increased platelet count may be translated into enhanced tumor growth. We examined the relation between platelet count and several prognostic variables in patients with esophageal cancer. Patients and Methods: Three hundred and eighty-one cases with esophageal cancer that underwent esophagectomy in a referral cancer institute during a 5-year period were studied retrospectively. The relation between preoperative platelet count and patient age, gender, site of tumor, presence of multiple cancers and clinicopathological characteristics including histological type, tumor size, depth of penetration (T), lymph node involvement (N), distant metastasis (M), degree of differentiation, presence of vascular, lymphatic and perineural invasion was examined. Results: Squamous cell carcinoma (SCC) constituted 93% and adenocarcinoma 7% of cases. Most of patients were in stage III, followed by stage II. The mean platelet count was 245±76 (× 109 /L). There was no statistically significant correlation between platelet counts with prognostic factors except a weak linear correlation between platelet count and and tumor size (P= 0.03, Pearson correlation coefficient: 0.16). Patients with adenocarcinoma had a higher platelet count than those with SCC (P= 0.003). Conclusion: Platelet count does not correlate with prognostic factors in esophageal cancer. However, it is significantly different between SCC and adenocarcinoma of esophagus.
Aminian, Ali; Karimian, Faramarz; Mirsharifi, Rasoul; Alibakhshi, Abbas; Dashti, Habibollah; Jahangiri, Yosra; Safari, Saeed; Ghaderi, Hamid; Noaparast, Morteza; Hasani, Sharareh M.; Mirsharifi, Alireza
Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity. PMID:23886488
Dai, Zhiyu; Zhou, Ti; Li, Cen; Qi, Weiwei; Mao, Yuling; Lu, Juling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Cai, Weibin; Yang, Zhonghan; Ma, Jianxing; Yang, Xia; Gao, Guoquan
Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. Evidence suggests an important role for the renin-angiotensin system in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). Therefore, we studied the presence of immunoreactive renin in renal biopsies and measured the concentrations of renin in cyst fluids. Normal kidneys and kidneys with renal artery stenosis were used for
Vicente E Torres; Kathleen A Donovan; Gloria Scicli; Keith E Holley; Stephen N Thibodeau; Oscar A Carretero; Tadashi Inagami; James A McAteer; Christopher M Johnson
At least two cellular processes are required for corneal epithelium homeostasis and wound repair: cell proliferation and cell-cell adhesion. These processes are delicately balanced to ensure the maintenance of normal epithelial function. During wound healing, these processes must be reprogrammed in coordination to achieve a rapid re-epithelialization. Basonuclin (Bnc1) is a cell-type-specific transcription factor expressed mainly in the proliferative keratinocytes
Xiaohong Zhang; Hung Tseng; Dong-Yan Jin
Our aim was to study the migration of retinal pigmented epithelium (RPE) into the retinal layer during infection of C57BL\\/6 mice with Toxoplasma gondii. Eyes from infected and non-infected animals were analyzed on the 60th day of infection by light and transmission electron microscopy. Non-infected eyes showed a normal morphology. In contrast, we observed free parasites in the retinal vasculature,
R. C. Tedesco; R. L. Smith; S. Corte-Real; K. S. Calabrese
In the current study, expression of the apoptotic calcium channel receptor P2X7 and prostate-specific antigen (PSA) levels were studied in biopsy cores from 174 patients as well as 20 radical prostatectomy cases. In clinical biopsies, we have previously demonstrated that P2X1 and P2X2 calcium channel receptors are absent from normal prostate epithelium that does not progress to prostate cancer within
Michael Slater; Suzanne Danieletto; Julian A. Barden
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.
Russell, C.O.; Pope, C.E.; Gannan, R.M.; Allen, F.D.; Velasco, N.; Hill, L.D.
OBJECTIVE:The efficacy of empirical esophageal dilation for nonobstructive dysphagia (NOD) is unknown. Our aim was to assess the efficacy and safety of empirical dilation with a large bougie in patients with NOD.METHODS:Patients with NOD (normal barium swallow, free passage of a 13-mm barium pill, and normal esophagogastroduodenoscopy) were randomized to dilation with either a 50-Fr (Group A) or 26-Fr (Group
Victor J. Colon; Michele A. Young; Francisco C. Ramirez
Background/Aim: Current guidelines recommend screening cirrhotic patients with an endoscopy to detect esophageal varices and to institute prophylactic measures in patients with large esophageal varices. In this study, we aimed at identifying non-endoscopic parameters that could predict the presence and grades of esophageal varices. Patients and Methods: In a prospective study, 229 newly diagnosed patients with liver cirrhosis, without a history of variceal bleeding, were included. Demographic, clinical, biochemical and ultrasonographic parameters were recorded. Esophageal varices were classified as small and large, at endoscopy. Univariate analysis and multivariate logistic regression analysis were done to identify independent predictors for the presence and grades of varices. Results: Of the 229 patients (141 males; median age 42 years; range 17-73 years) with liver cirrhosis, 97 (42.3%) had small and 81 (35.4%) had large varices. On multivariate analysis, low platelet count (Odd’s Ratio [OR], 4.3; 95% confidence interval [CI], 1.2-14.9), Child Pugh class B/C (OR, 3.3; 95% CI, 1.8-6.3), spleen diameter (OR, 4.3; 95% CI, 1.6-11.9) and portal vein diameter (OR, 2.4; 95% CI, 1.1-5.3) were independent predictors for the presence of varices. Likewise, for the presence of large esophageal varices, low platelet count (OR, 2.7; 95% CI, 1.4-5.2), Child Pugh class B/C (OR, 3.8; 95% CI, 2.3-6.5) and spleen diameter (OR, 3.1; 95% CI, 1.6-6.0) were the independent risk factors. Conclusion: The presence and higher grades of varices can be predicted by a low platelet count, Child-Pugh class B/C and spleen diameter. These may be considered as non-endoscopic predictors for the diagnosis and management of large grade varices.
Cherian, Jijo V.; Deepak, Nandan; Ponnusamy, Rajesh Prabhu; Somasundaram, Aravindh; Jayanthi, V.
We hypothesized that, in esophageal squamous epithelial cells, there are differences among individuals in the signal transduction pathways activated by acid reflux that might underlie the development of Barrett's esophagus. To explore that hypothesis, we immortalized nonneoplastic, esophageal squamous cells from patients with gastroesophageal reflux disease (GERD) with (NES-B3T) and without (NES-G2T) Barrett's esophagus and used those cells to study acid effects on MAPK proteins. During endoscopy in patients with GERD with and without Barrett's esophagus, we took biopsy specimens from the distal squamous esophagus to study MAPK proteins before and after esophageal perfusion with 0.1 N HCl. We used immunoblotting and Western blotting to study MEK1/2 phosphorylation at two activating sites (serines 217/221), MEK1 phosphorylation at an inhibitory site (threonine 286), and MEK1/2 activity. After acid exposure, both cell lines exhibited increased MEK1/2 phosphorylation at the activating sites; the NES-B3T cells had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the NES-G2T cells showed an acid-induced increase in MEK1/2 activity. Similarly, in the squamous epithelium of patients with GERD with and without Barrett's esophagus, acid perfusion increased MEK1/2 phosphorylation at the activating sites in both patient groups; the Barrett's patients had higher levels of MEK1 phosphorylation at the inhibitory site, however, and only the patients without Barrett's demonstrated an acid-induced increase in ERK1/2 phosphorylation. In esophageal squamous cell lines and biopsies from patients with GERD with and without Barrett's esophagus, we have found differences in MAPK pathways activated by acid exposure. We speculate that these differences might underlie the development of Barrett's metaplasia. PMID:18617556
Zhang, Hui Ying; Zhang, Xi; Chen, Xi; Thomas, Deena; Hormi-Carver, Kathy; Elder, Frederick; Spechler, Stuart J; Souza, Rhonda F
Distal airway epithelium is widely believed to secrete ions and liquid into the airspace, although this process has never been demonstrated in intact small airways. To determine the characteristics of active ion transport in distal airway epithelium, the effects of selective inhibitors of active Na+ absorption and Cl- secretion on the bioelectric properties of intact proximal bronchiolar epithelium were evaluated. Large bronchioles (450-1,200 microns outside diameter, 1.5-5.0 mm length) were excised from 4- to 8-wk-old pigs, cannulated with glass microcannulas, and perfused. Transepithelial potential difference (PD), short-circuit current (Isc), and resistance (Rm) were measured by cable analysis. In 14 tissues, resting PD, Isc, and Rm were -3.4 +/- 0.4 mV (lumen negative), 19.6 +/- 4.7 microA/cm2, and 255 +/- 50 omega.m2, respectively. The conductive Na+ channel blocker amiloride (10 microM) significantly (P < 0.05) reduced PD and Isc by 37 and 41% and significantly increased Rm by 23% in seven tissues. Subsequent bumetanide (10 microM), a blocker of active Cl- secretion through inhibition of Na(+)-K(+)-2Cl- cotransport, significantly reduced the amiloride-insensitive PD and Isc by 41 and 50%, whereas Rm significantly increased 15%. Because amiloride is known to induce Cl- secretion, the order of drug addition was reversed to determine the fractional contribution of active Cl- secretion to the resting PD, Isc, and Rm. In seven different bronchioles, bumetanide did not significantly affect PD, Isc, or Rm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8048545
Ballard, S T; Taylor, A E
The authors have studied the expression of keratin 19 in normal oral mucosa and in oral lesions exhibiting a range of histopathologic changes that are thought to precede squamous cell carcinoma. Formalin-fixed, paraffin-embedded sections were pretreated with pronase and stained with a K19-specific antibody by the avidin-biotin immunoperoxidase method. In nonkeratinized mucosa, whether normal or benign hyperplastic, K19 was detectable in the basal cell layer. In keratinized mucosa, whether normal or benign hyperplastic, there was no detectable K19. All lesions from any oral site that exhibited atypia diagnosed from hematoxylin and eosin stained sections as moderate-to-severe dysplasia or carcinoma in situ, whether hyperkeratotic or not, stained strongly for K19 in the basal and suprabasal cell layers. The number of cell layers that were K19-positive correlated with the level in the epithelium to which dysplasia persisted. Suprabasal K19 staining tended to occur in regions of the epithelium in which expression of the terminal differentiation protein involucrin was delayed or absent. Thus, K19 expression may be linked to the retention of stem cell character or a state otherwise uncommitted to terminal squamous differentiation. Suprabasal K19 staining is clearly correlated with premalignant change in oral epithelium and therefore promises to be a useful tool in oral histopathologic diagnosis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5
Lindberg, K.; Rheinwald, J. G.
There is currently a major focus on the role of the gut barrier function in balancing mucosal immune responses. Increased epithelial permeability for exogenous antigens is a crucial primary or secondary event in the pathogenesis of several disorders affecting body surfaces and beyond. The epithelial gate-keeper function is determined by the individual's age (e.g. preterm vs. term infant), diet, genetics, mucus composition, interactions between mast cells, nerves and neuropeptides, concurrent infection, the commensal microbiota and the epithelium-shielding effect of secretory IgA (SIgA) antibodies provided by breast milk or produced in the individual's gut. The integrity of the epithelial barrier furthermore depends on homeostatic regulatory mechanisms, including mucosal induction of regulatory T cells, where commensal microbiota-host interactions apparently play decisive roles. Thus, both extrinsic and intrinsic factors have been identified that may have an impact on the dynamics of the epithelial cell-cell junctions in the gut and thereby increase or reduce paracellular permeability. Experiments have shown that SIgA normally cooperates with innate defence factors to protect the epithelium and reinforce its barrier function. In the absence of SIgA commensal gut bacteria overstimulate innate epithelial immunity at the expense of expression of genes that regulate fat and carbohydrate metabolism, resulting in an epithelial gene signature that correlates with the development of lipid malabsorption. This shows that the intestinal epithelial barrier is a cross-road between defence and nutrition, and that SIgA is essential to keep the balance between these two functions. PMID:23257015
Background Motilin, an endogenous gastrointestinal (GI) hormone, increases upper gastrointestinal tract motility and is associated with phase III of the gastric migrating motor complex. The motilin receptor agonist, atilmotin, at doses of 6, 30 or 60 µg intravenously (IV), increases the early phase of gastric emptying. Prior studies at higher doses of 100–450 µg IV demonstrated that some subjects developed noncardiac chest pain. Aims The aim of this study is to determine the effects of atilmotin on esophageal, lower esophageal sphincter (LES), and gastric contractility and the development of esophageal-related symptoms. Methods Ten healthy volunteers underwent esophageal manometry to study the effects of atilmotin on upper GI motility. Five subjects were studied on three separate days following administration of saline placebo and subsequent IV bolus dose of atilmotin (6, 30 or 150 µg). Another five subjects were studied at the highest dose (150 µg). Results Atilmotin at 150 µg increased proximal gastric pressure by 6.5 mmHg (P = 0.001 compared with placebo). Atilmotin increased LES pressure at all studied doses; LES pressure increased from 24 ± 2 mmHg following placebo injection to 34 ± 4 mmHg following a 30 µg dose of atilmotin (P = 0.007). In the esophagus, atilmotin increased the percentage of failed swallows at the highest dose studied. Failed swallows increased from 17 ± 7% following placebo injection to 36 ± 7% following a 150 µg dose of atilmotin (P = 0.016). Atilmotin decreased distal esophageal contractile amplitude only at the highest dose studied, from 69 ± 8 mmHg (placebo) to 50 ± 5 mmHg following 150 µg atilmotin (P = 0.018). There were no serious adverse effects or episodes of chest pain with atilmotin. Conclusions Atilmotin affects esophageal, LES, and gastric motility. LES and gastric pressures were increased, whereas there was disruption of esophageal peristalsis characterized by lower amplitude and failed contractions.
AIM: To determine if esophageal capsule endoscopy (ECE) is an adequate diagnostic alternative to esophagogastroduodenoscopy (EGD) in pre-bariatric surgery patients. METHODS: We conducted a prospective pilot study to assess the diagnostic accuracy of ECE (PillCam ESO2, Given Imaging) vs conventional EGD in pre-bariatric surgery patients. Patients who were scheduled for bariatric surgery and referred for pre-operative EGD were prospectively enrolled. All patients underwent ECE followed by standard EGD. Two experienced gastroenterologists blinded to the patient’s history and the findings of the EGD reviewed the ECE and documented their findings. The gold standard was the findings on EGD. RESULTS: Ten patients with an average body mass index of 50 kg/m2 were enrolled and completed the study. ECE identified 11 of 14 (79%) positive esophageal/gastroesophageal junction (GEJ) findings and 14 of 17 (82%) combined esophageal and gastric findings identified on EGD. Fisher’s exact test was used to compare the findings and no significant difference was found between ECE and EGD (P = 0.64 for esophageal/GEJ and P = 0.66 for combined esophageal and gastric findings respectively). Of the positive esophageal/GEJ findings, ECE failed to identify the following: hiatal hernia in two patients, mild esophagitis in two patients, and mild Schatzki ring in two patients. ECE was able to identify the entire esophagus in 100%, gastric cardia in 0%, gastric body in 100%, gastric antrum in 70%, pylorus in 60%, and duodenum in 0%. CONCLUSION: There were no significant differences in the likelihood of identifying a positive finding using ECE compared with EGD in preoperative evaluation of bariatric patients.
Shah, Ashish; Boettcher, Erica; Fahmy, Marianne; Savides, Thomas; Horgan, Santiago; Jacobsen, Garth R; Sandler, Bryan J; Sedrak, Michael; Kalmaz, Denise
Background Eosinophilic esophagitis (EE) is an emerging worldwide disease that mimics gastroesophageal reflux disease. Objective Early studies have suggested that esophageal eosinophilia occurs in association with T helper type 2 allergic responses, yet the local and systemic expression of relevant cytokines has not been well characterized. Methods A human inflammatory cytokine and receptor PCR array containing 84 genes followed by PCR validation and multiplex arrays were used to quantify cytokine mRNA in esophageal biopsies and blood levels. Results Esophageal transcripts of numerous chemokines [e.g. CCL1, CCL23, CCL26 (eotaxin-3), CXCL1, and CXCL2], cytokines (e.g. IL13 and ABCF1), and cytokine receptors (e.g. IL5RA) were induced at least 4-fold in individuals with EE. Analysis of esophageal biopsies (n=288) revealed that eotaxin-3 mRNA level alone had 89% sensitivity for distinguishing EE from non-EE individuals. The presence of allergy was associated with significantly increased esophageal expression of IL4 and IL5 mRNA in active EE patients. We identified 8 cytokines (IL-4, IL-13, IL-5, IL-6, IL-12p70, CD40L, IL-1?, and IL-17) whose blood levels retrospectively distinguished 12 non-EE from 13 EE patients with 100% specificity and 100% sensitivity. When applied to a blinded, prospectively recruited group of 36 patients, the cytokine panel scoring system had a 79% positive predictive value, 68% negative predictive value, 61% sensitivity, and 83% specificity for identifying EE. Conclusion Evidence is presented that IL13 and IL5 associate with eosinophil and eotaxin-3 levels, indicating the key role of adaptive Th2 immunity in regulating eotaxin-3-driven esophageal eosinophilia in the absence of a consistent systemic change in cytokines.
Blanchard, Carine; Stucke, Emily M.; Rodriguez-Jimenez, Beatriz; Burwinkel, Karen; Collins, Margaret H.; Ahrens, Annette; Alexander, Eileen S.; Butz, Bridget K. Buckmeier; Jameson, Sean C.; Kaul, Ajay; Franciosi, James P.; Kushner, Jonathan P.; Putnam, Philip E.; Abonia, J. Pablo; Rothenberg, Marc E.
The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and enzymatic O-linked glycosylation (O-GlcNAcation) through the addition of O-linked-?-N-acetylglucosamine in esophageal squamous cell carcinoma. OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL2, respectively. The relationship between pathological and clinical factors of patients was analyzed. We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues. RL2 antibody level was positively correlated with OGT expression, and the metastasis of lymph node, which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma. In conclusion, OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma. O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.
Qiao, Zhe; Dang, Chengxue; Zhou, Bin; Li, Shaomin; Zhang, Wei; Jiang, Jiantao; Zhang, Jin; Kong, Ranran; Ma, Yuefeng
A custom-developed ultrahigh resolution optical coherence tomography with an axial resolution of 1.1 ?m in corneal tissue was used to characterize thickness and light scatter of the epithelium and Bowman's layer in keratoconic (KC) cornea noninvasively. A 4-mm wide vertical corneal section around the apex in nine KC and eight normal eyes was imaged in vivo. The epithelium and Bowman's layer were visualized and their thickness profiles were quantified. Scatter was quantified based on the sensitivity normalized mean signal intensity distribution. Average mean thickness of the epithelium and Bowman's layer in KC eyes was significantly smaller (p<0.05) than the normal eyes. The epithelium thickness variation across a central 3-mm cornea was significantly larger in KC eyes than in normal eyes. The scatter in KC eyes was significantly increased only for Bowman's layer. The changes observed in this study could improve our understanding of the underlying disease mechanism of KC and can provide new indications for early disease diagnosis.
Yadav, Rahul; Kottaiyan, Ranjini; Ahmad, Kamran; Yoon, Geunyoung
Bone morphogenetic proteins (BMPs) are members of the TGF superfamily of cytokines that are involved in develop- ment, differentiation, and disease. In an analysis of normal ovarian surface epithelium (OSE) and ovarian cancer (OC) cells, we observed BMP4 mRNA expression and found that primary OC cells produce mature BMP4. In addition, each member of the downstream signaling pathway was expressed
TREVOR G. SHEPHERD; MARK W. NACHTIGAL
Esophageal squamous cell carcinoma (ESCC) is a common malignancy and one of the more difficult diseases to diagnose in Japan due to its poor prognosis. MicroRNAs are small non-coding RNAs of 21–23 nucleotides that regulate gene expression. MicroRNA-34b (miR-34b) has been reported to be overexpressed in various types of cancer. However, its role in ESCC has yet to be extensively studied. The present study investigated the expression of miR-34b in 88 ESCC patients. The miR-34b expression in ESCC was significantly higher than that in the corresponding normal esophageal mucosa. It was more highly expressed in tumors with more advanced stages. However, its expression did not correlate with the p53 status. Transfection of anti-miR-34b to the ESCC cells suppressed cell growth in vitro. These results suggest an oncogenic role of miR in ESCC.
HARATA, KOSHIRO; ISHIGURO, HIDEYUKI; KUWABARA, YOSHIYUKI; KIMURA, MASAHIRO; MITSUI, AKIRA; OGAWA, RYO; KATADA, TAKEYASU; TANAKA, TATSUYA; SHIOZAKI, MIDORI; FUJII, YOSHITAKA
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.
Goff, J.S.; Adcock, K.A.; Schmelter, R.
Various neurotransmitter-related biochemical features of the separated pigment epithelium and neural retina of the cow have been examined. The pigment epithelium contains high affinity binding sites for several pharmacological agents thought to attach to neurotransmitter receptor sites with a high degree of specificity. Thus, serotonergic, adrenergic and opiate receptors appear to be present in the pigment epithelium. Serotonin has also been detected in this region. Several neuropeptides were found in the pigment epithelium. Relatively large amounts of neurotensin and met-enkephalin were present, but substance P was not detected. PMID:20487951
Bondy, S C; Ali, S F; Hong, J S; Wilson, W E; Fletcher, T; Chader, G
The aggressive behavior of esophageal cancer leads to a low survival rate for patients with this disease. Isolated esophageal\\u000a cancer cells seem to have the potential for regrowth and metastasis. To control the metastasis of esophageal carcinoma, detailed\\u000a analysis of various molecular and biological factors should be done in each patient. Recent progress in molecular biology\\u000a has revealed that oncogenes,
Yutaka Shimada; Fumiaki Sato
Background Studies indicate that gastro-esophageal reflux disease (GERD) is associated with obesity, smoking, esophagitis, diet, and\\u000a lifestyle. Aim To identify risk factors associated with GERD among patients presenting to a tertiary GI clinic in Italy. Methods Patients with a first diagnosis of GERD based on heartburn and\\/or regurgitation and\\/or esophagitis at the endoscopic examination\\u000a were enrolled. A control group with
Maria Pina Dore; Emmanouil Maragkoudakis; Ken Fraley; Antonietta Pedroni; Vincenza Tadeu; Giuseppe Realdi; David Y. Graham; Giuseppe Delitala; Hoda M. Malaty
. After we incidentally found on CT extensive esophageal fat accumulations in a patient with long-term use of steroids, we\\u000a prospectively evaluated during a 6-month period all CT studies of the chest for esophageal lipomatosis and related the findings\\u000a to the possible use of steroids. The diagnosis of esophageal fat on CT was made by density measurements or if too
J. Bogaert; F. Rosseel; S. Verhaegen; J. Verschakelen
Gut motility disorders and altered pain perception were reported in patients with irritable bowel syndrome (IBS). To verify foregut involvement in IBS, we studied 30 patients using esophageal manometry and 24-hr pH monitoring of the distal esophagus. Two subgroups of patients underwent esophageal provocative tests (bethanechol 50 µg\\/kg subcutaneously and esophageal balloon distension test). Twelve healthy volunteers formed a control
Mario Costantini; Giacomo Carlo Sturniolo; Giovanni Zaninotto; Renata D'Incà; Rita Polo; Remo Naccarato; Ermanno Ancona
Carbonated soft drinks (CSDs) have been associated with gastroesophageal refl ux, an established risk factor for esophageal adenocarcinoma. As both CSD consumption and esophageal ade- nocarcinoma incidence have sharply increased in recent decades, we exam- ined CSD as a risk factor for esophageal and gastric cancers in a U.S. multi- center, population-based case-control study. Associations between CSD intake and risk
Susan T. Mayne; Harvey A. Risch; Robert Dubrow; Wong-Ho Chow; Marilie D. Gammon; Thomas L. Vaughan; Lauren Borchardt; Janet B. Schoenberg; Janet L. Stanford; A. Brian West; Heidi Rotterdam; William J. Blot; Joseph F. Fraumeni
Background/Aims We assessed the bolus transit and motility characteristics in gastroesophageal reflux disease (GERD) patients with abnormal esophageal pH monitoring. Methods We retrospectively reviewed the combined impedance-esophageal manometry data from consecutive patients who had abnormal acid exposure during 24-hour esophageal pH monitoring. We compared these data to the results from functional heartburn (FH) and asymptomatic volunteers. Results The data from 33 GERD patients (mean age of 51 years, 18 males), 14 FH patients (mean age of 51 years, one male), and 20 asymptomatic volunteers (mean age of 27 years, nine males) were analyzed. Ineffective esophageal motility was diagnosed in 10% of the volunteers, 21% of the FH patients, and 15% of the GERD patients. Ineffective contraction was more frequent in GERD and FH patients than in volunteers (16% and 20% vs 6%, respectively; p<0.05). Additionally, 10% of the volunteers, 21% of the FH patients and 36% of the GERD patients had an abnormal bolus transit. Complete bolus transit was less frequent, and bolus transit was slower in GERD patients than in volunteers for liquid (70% vs 85%) and viscous swallows (57% vs 73%). A longer acid clearance time was associated with abnormal bolus transit in the GERD group. Conclusions Patients with GERD have mild peristaltic dysfunction and incomplete and slower esophageal bolus transit. These conditions predispose them to prolonged acid contact with the esophagus.
Cho, Yu Kyung; Lim, Chul Hyun; Kim, Jin Su; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Kyu-Yong
CD166 is an Ig superfamily molecule that binds homotypically to itself and heterotypically to CD6. Interactions between CD6 and CD166 are important during immune development and in alloreactivity. CD166 is expressed at increased levels in selected cancers and in rheumatoid arthritis synovium. Knowledge that CD166 was expressed in normal human salivary epithelium led to these studies of CD166 and CD6 in diseased mouse salivary glands, that resemble pathology seen in the human disease, Sjögren's syndrome. We showed that in mouse salivary epithelium CD166 was expressed but that expression of CD166 did not necessarily predict its function. Recombinant soluble CD6-Ig bound to CD6 ligands (CD6L) on transformed and freshly isolated salivary epithelial cells. Cross-blocking studies showed that binding of CD6-Ig to salivary epithelium was in part dependent on CD166, but that CD6-Ig binding may also involve additional CD6L. Binding of CD6-Ig was sensitive to trypsin digestion but resistant to digestion by collagenase and sialidase. Anti-CD166 ab precipitated CD166 from salivary epithelium pre- and post-treatment with the pro-inflammatory cytokine IFN-gamma. In contrast CD6-Ig only precipitated CD166 from IFN-gamma treated cells. More extensive colocalization between CD166 and the actin cytoskeleton was observed in sialoadenitis epithelium compared to control. We conclude that during sialoadenitis, CD166 undergoes a gain of function, resulting in closer association with the actin cytoskeleton and increased capacity to bind CD6. We suggest that altered CD166 function may contribute to the pro-inflammatory milieu during sialoadenitis seen in Sjögren's syndrome. PMID:16418799
Abidi, Syed M A; Saifullah, Mohammad K; Zafiropulos, Marie D; Kaput, Cara; Bowen, Michael A; Cotton, Calvin; Singer, Nora G
Background The purpose of this study was to evaluate the association of multi-genotype polymorphisms with the stepwise progression of esophageal squamous cell cancer (ESCC) and the possibility of predicting those at higher risk. Methods A total of 1,004 subjects were recruited from Feicheng County, China, between Jan. 2004 and Dec. 2007 and examined by endoscopy for esophageal lesions. These subjects included 270 patients with basal cell hyperplasia (BCH), 262 patients with esophageal squamous cell dysplasia (ESCD), 226 patients with ESCC, and 246 controls with Lugol-voiding area but diagnosed as having normal esophageal squamous epithelial cells by histopathology. The genotypes for CYP2E1 G1259C, hOGG1 C326G, MTHFR C677T, MPO G463A, and ALDH2 allele genes were identified in blood samples collected from all participants. Results The alleles ALDH2 and MTHFR C677T were critical for determining individual susceptibility to esophageal cancer. Compared to the ALDH 1*1 genotype, the ALDH 2*2 genotype was significantly associated with increased risks of BCH, ESCD, and ESCC. However, the TT genotype of MTHFR C677T only increased the risk of ESCC. Further analysis revealed that the combination of the high-risk genotypes 2*2/1*2 of ALDH 2 and TT/TC of MTHFR C677T increased the risk of BCH by 4.0 fold, of ESCD by 3.7 fold, and ESSC by 8.72 fold. The generalized odds ratio (ORG) of the two combined genotypes was 1.83 (95%CI: 1.55-2.16), indicating a strong genetic association with the risk of carcinogenic progression in the esophagus. Conclusions The study demonstrated that the genotypes ALDH2*2 and MTHFR 677TT conferred elevated risk for developing esophageal carcinoma and that the two susceptibility genotypes combined to synergistically increase the risk.
Background Esophageal cancer accounts for a considerable proportion of carcinomas of the upper gastrointestinal tract in African Americans.\\u000a Our aim was to describe the epidemiology of esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EA) among\\u000a African Americans in the last five decades.\\u000a \\u000a \\u000a \\u000a \\u000a Methods A total of 601 records of patients with documented esophageal cancer between 1959 and 2007 at Howard University
Hassan Ashktorab; Zahra Nouri; Mehdi Nouraie; Hadi Razjouyan; Edward E. Lee; Ehsan Dowlati; El-Waleed El-Seyed; Adeyinka Laiyemo; Hassan Brim; Duane T. Smoot
Athymic mice grafted at birth with allogeneic thymic epithelium (TE) from day 10 embryos before hematopoietic cell colonization reconstitute normal numbers of T cells and exhibit full life-long tolerance to skin grafts of the TE haplotype. Intravenous transfers of splenic cells, from these animals to adult syngeneic athymic recipients, reconstitute T-cell compartments and the ability to reject third-party skin grafts. The transfer of specific tolerance to skin grafts of the TE donor strain, however, is not observed in all reconstituted recipients, and the fraction of nontolerant recipients increases with decreasing numbers of cells transferred. Furthermore, transfers of high numbers of total or CD4+ T cells from TE chimeras to T-cell receptor-anti-H-Y antigen transgenic immunocompetent syngeneic hosts specifically hinder the rejection of skin grafts of the TE haplotype that normally occurs in such recipients. These observations demonstrate (i) that mice tolerized by allogeneic TE and bearing healthy skin grafts harbor peripheral immunocompetent T cells capable of rejecting this very same graft; and (ii) that TE selects for regulatory T cells that can inhibit effector activities of graft-reactive cells.
Modigliani, Y; Thomas-Vaslin, V; Bandeira, A; Coltey, M; Le Douarin, N M; Coutinho, A; Salaun, J
The movement of intravitreally injected tritiated water from the vitreous to the choroid was accelerated by the removal of intervening retina. Both rate of transfer and peak choroidal levels of the tracer were increased, but the proportion of the intravitreal dose recovered was unaltered. In contrast, the movement of tritiated water after diffuse damage to the retinal pigment epithelium by sodium iodate was similar to that of control eyes. The main resistance to the diffusion of this tracer from the vitreous to the choroid is the retina. The differential permeability of the retina and the retinal pigment epithelium may have a role in normal retinal adhesion.
Orr, G.; Goodnight, R.; Lean, J.S.
Dilatations are considered the election treatment for esophageal stenosis of different etiologies. Different methods of dilatation have been used through the years. Security and effectiveness are the main subjects when we choose a dilatation method. We present the results of the last 3 years that Savary-Guilliard have been used, with a guide wire probe, under endoscopic control. Six patients with postsurgical stenosis and 10 with post lye ingestion stenosis were treated with the above mentioned method. The site of stenosis is localized under flexible endoscopy, and a special guide wire probe is introduced to the stomach. Once the wire is in place, different diameter bougies are introduced until a firm resistance is felt or the desired diameter is reach. In complicated cases the progression of the wire was controlled by X-rays. A total of 208 dilatations have done in 16 patients over the last three years. Six patients with postsurgical stenosis needed from two to six dilatations for their cure. Of the 10 patients who ingest lye, none of them had needed a gastrostomy. Three of them have no dysphagia after 9, 13 and 13 dilatations. The other 7 are under dilatations every 6 weeks in 6 cases and every 4 weeks in one case, been all of them in the second year of treatment. All the dilatations have been performed under general anesthesia, as outpatients. We have not had any complication under this treatment. We have found that the Savary-Guilliard method is adequate for esophageal dilatations in pediatric population. Security and effectiveness are the main points of this procedure, there is no need for a gastrostomy, and the child will have a better quality of life. This procedure is less aggressive, and this will give a shorter postop period, with no complications and the child will have a longer period of normal life between dilatations. PMID:10198548
Asensio Llorente, M; Broto Mangues, J; Gil-Vernet Huguet, J M; Acosta Farina, D; Marhuenda Irastorza, C; Boix-Ochoa, J
Background Chlorine is a widely used toxic compound that is considered a chemical threat agent. Chlorine inhalation injures airway epithelial cells, leading to pulmonary abnormalities. Efficient repair of injured epithelium is necessary to restore normal lung structure and function. The objective of the current study was to characterize repair of the tracheal epithelium after acute chlorine injury. Methods C57BL/6 mice were exposed to chlorine and injected with 5-ethynyl-2?-deoxyuridine (EdU) to label proliferating cells prior to sacrifice and collection of tracheas on days 2, 4, 7, and 10 after exposure. Airway repair and restoration of a differentiated epithelium were examined by co-localization of EdU labeling with markers for the three major tracheal epithelial cell types [keratin 5 (K5) and keratin 14 (K14) for basal cells, Clara cell secretory protein (CCSP) for Clara cells, and acetylated tubulin (AcTub) for ciliated cells]. Morphometric analysis was used to measure proliferation and restoration of a pseudostratifi