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Sample records for normal esophageal epithelium

  1. Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

    PubMed Central

    Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

    2017-01-01

    AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation. PMID:28293090

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

    PubMed Central

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

    2016-01-01

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

  3. Sox9 drives columnar differentiation of esophageal squamous epithelium: a possible role in the pathogenesis of Barrett's esophagus.

    PubMed

    Clemons, Nicholas J; Wang, David H; Croagh, Daniel; Tikoo, Anjali; Fennell, Christina M; Murone, Carmel; Scott, Andrew M; Watkins, D Neil; Phillips, Wayne A

    2012-12-15

    The molecular mechanism underlying the development of Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma, remains unknown. Our previous work implicated sonic hedgehog (Shh) signaling as a possible driver of BE and suggested that bone morphogenetic protein 4 (Bmp4) and Sox9 were downstream mediators. We have utilized a novel in vivo tissue reconstitution model to investigate the relative roles of Bmp4 and Sox9 in driving metaplasia. Epithelia reconstituted from squamous epithelial cells or empty vector-transduced cells had a stratified squamous phenotype, reminiscent of normal esophagus. Expression of Bmp4 in the stromal compartment activated signaling in the epithelium but did not alter the squamous phenotype. In contrast, expression of Sox9 in squamous epithelial cells induced formation of columnar-like epithelium with expression of the columnar differentiation marker cytokeratin 8 and the intestinal-specific glycoprotein A33. In patient tissue, A33 protein was expressed specifically in BE, but not in normal esophagus. Expression of Cdx2, another putative driver of BE, alone had no effect on reconstitution of a squamous epithelium. Furthermore, epithelium coexpressing Cdx2 and Sox9 had a phenotype similar to epithelium expressing Sox9 alone. Our results demonstrate that Sox9 is sufficient to drive columnar differentiation of squamous epithelium and expression of an intestinal differentiation marker, reminiscent of BE. These data suggest that Shh-mediated expression of Sox9 may be an important early event in the development of BE and that the potential for inhibitors of the hedgehog pathway to be used in the treatment of BE and/or esophageal adenocarcinoma could be tested in the near future.

  4. Infradian biorhythms of mitotic activity esophageal epithelium in male Wistar rats.

    PubMed

    Diatroptov, M E; Makarova, O V

    2015-01-01

    Infradian rhythms of esophageal epithelium mitotic activity were studied in male Wistar rats of two age groups: 35-45 days (prepubertal) and 3-4 months (adults). Studies of the time course of esophageal epithelium mitotic indexes in adult males showed 4- and 12-day biorhythms, while prepubertal rats exhibited only 4-day infradian biorhythms of this parameter. Studies of the mitotic activity over long periods (3 years) showed 4.058- and 12.175-day periodicity of infradian biorhythms for this parameter, presumably due to external exposures synchronizing the biorhythms. Studies of the mean daily values of the Bz component of interplanetary magnetic field during the period of our research (2012-2013) showed rhythmicities analogous to changes in the mitotic activity of the epithelium. The minimum mitotic indexes were detected on the days of the most pronounced negative values of the interplanetary magnetic field Bz component.

  5. Detection of human cytomegalovirus in normal and neoplastic breast epithelium

    PubMed Central

    2010-01-01

    Introduction Human cytomegalovirus (HCMV) establishes a persistent life-long infection, and can cause severe pathology in the fetus and the immunocompromised host[1]. Breast milk is the primary route of transmission in humans worldwide, and breast epithelium is thus a likely site of persistent infection and/or reactivation, though this phenomenon has not previously been demonstrated. Increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. We hypothesized that persistent HCMV infection occurs in normal adult breast epithelium and that persistent viral expression might be associated with normal and neoplastic ductal epithelium. Methods Surgical biopsy specimens of normal breast (n = 38) breast carcinoma (n = 39) and paired normal breast from breast cancer patients (n = 21) were obtained. Specimens were evaluated by immunohistochemistry, in situ hybridization, PCR and DNA sequencing for evidence of HCMV antigens and nucleic acids. Results We detected HCMV expression specifically in glandular epithelium in 17/27 (63%) of normal adult breast cases evaluated. In contrast, HCMV expression was evident in the neoplastic epithelium of 31/32 (97%) patients with ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC) cases evaluated (p = 0.0009). Conclusions These findings are the first to demonstrate that persistent HCMV infection occurs in breast epithelium in a significant percentage of normal adult females. HCMV expression was also evident in neoplastic breast epithelium in a high percentage of normal and neoplastic breast tissues obtained from breast cancer patients, raising the possibility that viral infection may be involved in the neoplastic process. PMID:21429243

  6. Transcriptomic profiles differentiate normal rectal epithelium and adenocarcinoma.

    PubMed

    Hogan, J; Dejulius, K; Liu, X; Coffey, J C; Kalady, M F

    2015-05-01

    Adenocarcinoma is a histologic diagnosis based on subjective findings. Transcriptional profiles have been used to differentiate normal tissue from disease and could provide a means of identifying malignancy. The goal of this study was to generate and test transcriptomic profiles that differentiate normal from adenocarcinomatous rectum. Comparisons were made between cDNA microarrays derived from normal epithelium and rectal adenocarcinoma. Results were filtered according to standard deviation to retain only highly dysregulated genes. Genes differentially expressed between cancer and normal tissue on two-groups t test (P < 0.05, Bonferroni P value adjustment) were further analyzed. Genes were rank ordered in terms of descending fold change. For each comparison (tumor versus normal epithelium), those 5 genes with the greatest positive fold change were grouped in a classifier. Five separate tests were applied to evaluate the discriminatory capacity of each classifier. Genetic classifiers derived comparing normal epithelium with malignant rectal epithelium from pooled stages had a mean sensitivity and specificity of 99.6% and 98.2%, respectively. The classifiers derived from comparing normal and stage I cancer had comparable mean sensitivities and specificities (97% and 98%, respectively). Areas under the summary receiver-operator characteristic curves for each classifier were 0.981 and 0.972, respectively. One gene was common to both classifiers. Classifiers were tested in an independent Gene Expression Omnibus-derived dataset. Both classifiers retained their predictive properties. Transcriptomic profiles comprising as few as 5 genes are highly accurate in differentiating normal from adenocarcinomatous rectal epithelium, including early-stage disease.

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

    PubMed

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

    2008-01-01

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

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

    PubMed

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

    2013-05-01

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

  9. Effects of formaldehyde on normal xenotransplanted human tracheobronchial epithelium.

    PubMed Central

    Ura, H.; Nowak, P.; Litwin, S.; Watts, P.; Bonfil, R. D.; Klein-Szanto, A. J.

    1989-01-01

    Epithelial cells obtained from autopsies of full-term fetuses or infants less than 1 year old were isolated, amplified in primary cultures and inoculated in deepithelialized rat tracheas. These tracheas were then sealed and transplanted subcutaneously into irradiated athymic nude mice. Four weeks after transplantation the tracheal lumen was completely covered by epithelium, most of which was of mucociliary respiratory type. At this stage, tracheal transplants containing tracheobronchial epithelium from 20 different donors were exposed to silastic devices containing 0, 0.5, 1 and 2 mg paraformaldehyde. The tracheal transplants were examined histologically at 2, 4, 8, and 16 weeks after transplantation. Before sacrifice, all animals were injected with a single pulse of tritiated thymidine. Important epithelial alterations could be seen in the formaldehyde treated transplants with a maximum effect visible at 2 weeks after exposure. The highest dose of 2 mg produced, in most cases, numerous areas of epithelial erosion and inflammation whereas this effect was not as evident with the lower doses. All doses produced areas of hyperplastic epithelium alternating with areas of pleomorphic-atrophic epithelium. Although the differences in predominance of different types of epithelium was not clearly dose-dependent, the labeling index (LI) showed dose dependence between 2 and 4 weeks after initiation of exposure. The maximum mean LI was three to four times higher than normal, although in some focal hyperplastic-metaplastic lesions the LI was increased up to 20 times. These studies show that formaldehyde, although toxic at higher doses, is able to elicit at lower doses a proliferative response of the human respiratory epithelium that is not preceded by a massive toxic effect. This response is similar, although less intense than that of the rat respiratory epithelium in which formaldehyde proved to be a carcinogen. Images Figure 2 Figure 5 PMID:2913828

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

    PubMed

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

    2015-06-01

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

  11. Luminal hydrochloric acid stimulates rapid transepithelial ion fluxes in rodent esophageal stratified squamous epithelium.

    PubMed

    Lin, B R; Hsieh, H T; Lee, J M; Lai, I R; Chen, C F; Yu, L C H

    2008-09-01

    It remains unclear whether enhanced ion fluxes occur in the esophageal stratified squamous epithelium upon acid exposure. Rat esophageal tissues devoid of submucosal glands displayed basal short-circuit current (Isc) of 5.03 +/- 1.93 microA/cm(2) and lumen-negative potential difference (PD) in association with net absorption of Na+ and Cl-, and secretion of HCO3(-). Luminal hydrochloric acid (HCl) challenge (pH = 1.6) triggered an acute rise of the Isc and increment of negative PD to seven-fold of baseline, which was diminished in HCO3(-)-free, but not Na+- free buffer. The rise of Isc was inhibited by pretreatment with di-isothiocyanatostilbene-2, 2'-disulphonic acid (DIDS) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). Topical carbachol, capsaicin, forskolin or CFTR(inh)-172 had no effect on basal Isc.CFTR(inh)-172 did not reduce the acid-increased Isc. Functional ablation of capsaicin-sensitive nerves had no effect on the acid-induced Isc. The phenomenon of enhanced ion fluxes upon acid stimulation was confirmed in human esophageal specimens. Our results demonstrated that the mechanism of acid-induced rapid transepithelial ion fluxes is dependent on the presence of bicarbonate ions as well as functional anion transporters and Na+/H+ exchanger, but independent of cystic fibrosis transmembrane conductance regulator (CFTR). The capsaicin-sensitive and muscarinic-dependent nerve pathways did not play roles in the mechanism.

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

    PubMed Central

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

    2016-01-01

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

  13. Epithelium

    MedlinePlus

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

  14. Pure esophageal atresia with normal outer appearance: case report.

    PubMed

    Sanal, Murat; Haeussler, Beatrice; Tabarelli, Walther; Maurer, Kathrin; Sergi, Consolato; Hager, Josef

    2007-08-01

    Isolated esophageal atresia is characterized by a long segment between the 2 esophageal pouches. This article presents a case of pure esophageal atresia with a 1-cm-long segment at the midportion without discontinuity that resembled the subtype II3 according to the Kluth atlas. Resection of the atretic segment and primary anastomosis were performed successfully.

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

    PubMed

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

    2016-06-02

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

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

    EPA Science Inventory

    Abstract

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

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

    EPA Science Inventory


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

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

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

    PubMed

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

    2011-02-01

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

  19. ECM microenvironment regulates collective migration and local dissemination in normal and malignant mammary epithelium.

    PubMed

    Nguyen-Ngoc, Kim-Vy; Cheung, Kevin J; Brenot, Audrey; Shamir, Eliah R; Gray, Ryan S; Hines, William C; Yaswen, Paul; Werb, Zena; Ewald, Andrew J

    2012-09-25

    Breast cancer progression involves genetic changes and changes in the extracellular matrix (ECM). To test the importance of the ECM in tumor cell dissemination, we cultured epithelium from primary human breast carcinomas in different ECM gels. We used basement membrane gels to model the normal microenvironment and collagen I to model the stromal ECM. In basement membrane gels, malignant epithelium either was indolent or grew collectively, without protrusions. In collagen I, epithelium from the same tumor invaded with protrusions and disseminated cells. Importantly, collagen I induced a similar initial response of protrusions and dissemination in both normal and malignant mammary epithelium. However, dissemination of normal cells into collagen I was transient and ceased as laminin 111 localized to the basal surface, whereas dissemination of carcinoma cells was sustained throughout culture, and laminin 111 was not detected. Despite the large impact of ECM on migration strategy, transcriptome analysis of our 3D cultures revealed few ECM-dependent changes in RNA expression. However, we observed many differences between normal and malignant epithelium, including reduced expression of cell-adhesion genes in tumors. Therefore, we tested whether deletion of an adhesion gene could induce sustained dissemination of nontransformed cells into collagen I. We found that deletion of P-cadherin was sufficient for sustained dissemination, but exclusively into collagen I. Our data reveal that metastatic tumors preferentially disseminate in specific ECM microenvironments. Furthermore, these data suggest that breaks in the basement membrane could induce invasion and dissemination via the resulting direct contact between cancer cells and collagen I.

  20. Thoracoscopic long myotomy in the prone position to treat rapid esophageal contractions with normal latency.

    PubMed

    Nomura, Tsutomu; Iwakiri, Katsuhiko; Matsutani, Takeshi; Hagiwara, Nobutoshi; Fujita, Itsuro; Nakamura, Yoshiharu; Kawami, Noriyuki; Miyashita, Masao; Uchida, Eiji

    2015-04-01

    A 56-year-old woman with an 8-year history of dysphagia and chest pain received a diagnosis of diffuse esophageal spasm by esophageal high-resolution manometry (HRM). Approximately 2 years of medical therapy was ineffective, and the patient's symptoms were worsening. Therefore, surgery was considered to be the most optimal treatment for this patient. The right thoracoscopic approach was selected because a long myotomy from the distal to proximal level of the esophagus was needed based on the HRM findings. The operation was performed in the prone position with establishment of pneumothorax. The total length of the myotomy was 16 cm, and the operation was finished within 2 hours. After the operation, the symptoms were considerably improved and no contractions were detected by HRM. The HRM findings before the operation were classified as rapid contractions with normal latency based on the 2012 Chicago classification of esophageal motility. Treatment for patients with rapid esophageal contractions with normal latency has not been previously described; however, treatment for diffuse esophageal spasm was considered to be pertinent to this patient. In conclusion, right thoracoscopic esophageal long myotomy in the prone position with establishment of pneumothorax may be useful when a proximal-level esophagomyotomy is required based on preoperative mapping by HRM.

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

    PubMed Central

    Knowles, M; Gatzy, J; Boucher, R

    1983-01-01

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

  2. Infrared spectroscopic characteristics of normal and malignant colonic epithelium

    NASA Astrophysics Data System (ADS)

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

    1998-04-01

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

  3. Esophagitis

    MedlinePlus

    ... irritates the tissue. This problem is called gastroesophageal reflux (GERD). An autoimmune disorder called eosinophilic esophagitis also ... include: Cough Difficulty swallowing Painful swallowing Heartburn (acid reflux) Hoarseness Sore throat Exams and Tests The doctor ...

  4. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    PubMed

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

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

    PubMed

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

    2015-03-01

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

  6. Comparative proteome analysis of human esophageal cancer and adjacent normal tissues

    PubMed Central

    Yazdian–Robati, Rezvan; Ahmadi, Homa; Riahi, Maryam Matbou; Lari, Parisa; Aledavood, Seyed Amir; Rashedinia, Marzieh; Abnous, Khalil; Ramezani, Mohammad

    2017-01-01

    Objective(s): Ranking as the sixth commonest cancer, esophageal squamous cell carcinoma (ESCC) represents one of the leading causes of cancer death worldwide. One of the main reasons for the low survival of patients with esophageal cancer is its late diagnosis. Materials and Methods: We used proteomics approach to analyze ESCC tissues with the aim of a better understanding of the malignant mechanism and searching candidate protein biomarkers for early diagnosis of esophageal cancer. The differential protein expression between cancerous and normal esophageal tissues was investigated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Then proteins were identified by matrix-assisted laser desorption/ ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS) and MASCOT web based search engine. Results: We reported 4 differentially expressed proteins involved in the pathological process of esophageal cancer, such as annexinA1 (ANXA1), peroxiredoxin-2 (PRDX2), transgelin (TAGLN) andactin-aortic smooth muscle (ACTA2). Conclusion: In this report we have introduced new potential biomarker (ACTA2). Moreover, our data confirmed some already known markers for EC in our region. PMID:28392898

  7. Relationship between multiple water swallows and gastroesophageal reflux in patients with normal esophageal motility.

    PubMed

    Choi, Y J; Park, M I; Park, S J; Moon, W; Kim, S E; Yoo, C H; Kwon, H J

    2015-01-01

    Multiple water swallows (MWS) stimulates neural inhibition, resulting in abolition of contractions in the esophageal body and complete lower esophageal sphincter relaxation, which is followed by peristalsis and the lower esophageal sphincter contraction. We assessed the relationship between MWS and gastroesophageal reflux in patients with esophageal symptoms and with normal findings by high-resolution manometry (HRM). We retrospectively reviewed the clinical records of patients who underwent HRM and a 24-hour ambulatory impedance-pH study. Correlation between the findings of the impedance-pH study and abnormal MWS responses without motility disorders was evaluated. Independent t-tests were used for statistical analysis. Of 28 patients, 20 (71%) had abnormal MWS responses: four (20%) had abnormal responses during MWS, six (30%) had abnormal responses after MWS, and 10 (50%) had abnormal responses both during and after MWS. Total acid exposure times were significantly longer in patients with abnormal MWS responses than in patients with normal MWS responses. In particular, upright acid exposure time and all reflux percent times were significantly longer in patients with abnormal MWS responses. However, bolus clearance time and longest reflux episode were not different between the two groups. Abnormal MWS responses predicted increased acid exposure times in patients with normal findings of HRM by the Chicago classification.

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

    PubMed

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

    2016-04-01

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

  9. Progression of Barrett’s esophagus toward esophageal adenocarcinoma: an overview

    PubMed Central

    Schoofs, Nele; Bisschops, Raf; Prenen, Hans

    2017-01-01

    In Barrett’s esophagus, normal squamous epithelium is replaced by a metaplastic columnar epithelium as a consequence of chronic gastroesophageal reflux disease. There is a strong association with esophageal adenocarcinoma. In view of the increasing incidence of esophageal adenocarcinoma in the western world, it is important that more attention be paid to the progression of Barrett’s esophagus toward esophageal adenocarcinoma. Recently, several molecular factors have been identified that contribute to the sequence towards adenocarcinoma. This might help identify patients at risk and detect new targets for the prevention and treatment of esophageal adenocarcinoma in the future. PMID:28042232

  10. Herpetic esophagitis

    SciTech Connect

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

    1981-12-01

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

  11. Loss of imprinting of the insulin-like growth factor II (IGF2) gene in esophageal normal and adenocarcinoma tissues.

    PubMed

    Zhao, Ronghua; DeCoteau, John F; Geyer, C Ronald; Gao, Mei; Cui, Hengmi; Casson, Alan G

    2009-12-01

    To evaluate loss of imprinting (LOI) and expression of the IGF2 gene in matched esophageal normal and adenocarcinoma tissues, we studied a prospective cohort of 77 patients who underwent esophageal resection between 1998 and 2003. IGF2 imprinting status was determined by reverse transcription-polymerase chain reaction (PCR) following ApaI digestion, and quantitative PCR was used to evaluate IGF2 expression, which was correlated with clinicopathologic findings, disease-free and overall survival. In total, 32% (14/44) of informative tissues showed loss of IGF2 imprinting, with a strong correlation between the tumor and normal esophageal epithelia (Kappa = 0.89, P < 0.01). Normal epithelia with LOI had increased expression of IGF2 [median: 2.91, 95% confidence interval (CI): 0.93-5.06] compared with imprinted normal epithelia (median: 1.13, 95% CI: 0.85-1.39) (P = 0.03). In contrast, tumors with LOI had significantly reduced IGF2 expression (median: 1.87, 95% CI: 0.53-5.21) compared with normally imprinted tumors (median: 6.79, 95% CI: 3.39-15.89) (P = 0.016). Patients below the age of 65 years with normally imprinted tumors had significantly reduced 5 year disease-free survival (DFS) (24%) compared with patients whose tumors had LOI for IGF2 (55%) (P = 0.03). Cox regression analysis showed that IGF2 overexpression was associated with significantly reduced disease-free survival (P = 0.04). We conclude that in a subgroup of younger patients, loss of IGF2 imprinting was associated with improved outcome following esophageal resection. Expression of IGF2 in esophageal adenocarcinoma and normal esophageal epithelia depended on imprinting status and tissue type, suggesting novel molecular regulatory mechanisms in esophageal tumorigenesis.

  12. Genes involved in epithelial differentiation and development are differentially expressed in oral and genital lichen planus epithelium compared to normal epithelium.

    PubMed

    Danielsson, Karin; Coates, Philip J; Ebrahimi, Majid; Nylander, Elisabet; Wahlin, Ylva Britt; Nylander, Karin

    2014-09-01

    Lichen planus (LP) is a chronic mucocutaneous disease with unknown cause. Patients with LP often have both oral and genital lesions, but these conditions are often considered as separate diseases and treated accordingly. To find out which genes are differently expressed in mucosal LP compared to normal mucosa and establish whether oral and genital LP are in fact the same disease, whole genome expression analysis was performed on epithelium from 13 patients diagnosed with oral and/or genital LP and normal controls. For confirmation of keratin 4 and corneodesmosin expression, quantitative reverse-transcription PCR and immunohistochemistry were used. Many genes involved in epithelial development and differentiation are differently expressed in epithelium from LP compared to normal epithelium. Several of the differentially expressed genes are common for oral and genital LP and the same biological processes are altered which supports the fact that oral and genital LP are manifestations of the same disease. The change in gene expression indicates that differentiation is altered leading to changes in the epithelial barrier.

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

    PubMed

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

    2011-02-01

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

  14. Surfactant protein A expression in human normal and neoplastic breast epithelium.

    PubMed

    Braidotti, P; Cigala, C; Graziani, D; Del Curto, B; Dessy, E; Coggi, G; Bosari, S; Pietra, G G

    2001-11-01

    We studied the presence of surfactant protein A (Sp-A) immunoreactivity and messenger RNA in 62 normal and abnormal breast samples. Sections were immunostained with polyclonal anti-Sp-A antibody. The association between Sp-A immunoreactivity and histologic grade of 32 invasive ductal carcinomas was assessed by 3 pathologists who scored the intensity of Sp-A immunoreactivity times the percentage of tumor immunostained; individual scores were averaged, and the final scores were correlated with tumor grade, proliferative index, and expression of estrogen and progesterone receptors. Strong Sp-A immunoreactivity was present at the luminal surface of ductal epithelial cells in normal breast samples and in benign lesions; carcinomas displayed variable immunoreactivity, inversely proportional to the degree of differentiation. Sp-A messenger RNA was detected by reverse transcriptase-polymerase chain reaction in 3 of 3 normal breast samples and 9 of 9 carcinomas. The significance of Sp-A expression in breast epithelium requires further study; possibly it has a role in native host defense or epithelial differentiation.

  15. Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing.

    PubMed

    Radovich, Milan; Clare, Susan E; Atale, Rutuja; Pardo, Ivanesa; Hancock, Bradley A; Solzak, Jeffrey P; Kassem, Nawal; Mathieson, Theresa; Storniolo, Anna Maria V; Rufenbarger, Connie; Lillemoe, Heather A; Blosser, Rachel J; Choi, Mi Ran; Sauder, Candice A; Doxey, Diane; Henry, Jill E; Hilligoss, Eric E; Sakarya, Onur; Hyland, Fiona C; Hickenbotham, Matthew; Zhu, Jin; Glasscock, Jarret; Badve, Sunil; Ivan, Mircea; Liu, Yunlong; Sledge, George W; Schneider, Bryan P

    2014-01-01

    Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos.

  16. Analysis of spatial heterogeneity in normal epithelium and preneoplastic alterations in mouse prostate tumor models

    PubMed Central

    Valkonen, Mira; Ruusuvuori, Pekka; Kartasalo, Kimmo; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

    2017-01-01

    Cancer involves histological changes in tissue, which is of primary importance in pathological diagnosis and research. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue with all its variables. On the other hand, understanding connections between genetic alterations and histological attributes requires development of enhanced analysis methods suitable also for small sample sizes. Here, we set out to develop computational methods for early detection and distinction of prostate cancer-related pathological alterations. We use analysis of features from HE stained histological images of normal mouse prostate epithelium, distinguishing the descriptors for variability between ventral, lateral, and dorsal lobes. In addition, we use two common prostate cancer models, Hi-Myc and Pten+/− mice, to build a feature-based machine learning model separating the early pathological lesions provoked by these genetic alterations. This work offers a set of computational methods for separation of early neoplastic lesions in the prostates of model mice, and provides proof-of-principle for linking specific tumor genotypes to quantitative histological characteristics. The results obtained show that separation between different spatial locations within the organ, as well as classification between histologies linked to different genetic backgrounds, can be performed with very high specificity and sensitivity. PMID:28317907

  17. Intracellular Fas ligand in normal and malignant breast epithelium does not induce apoptosis in Fas-sensitive cells

    PubMed Central

    Ragnarsson, G B; Mikaelsdottir, E K; Vidarsson, H; Jónasson, J G; Ólafsdóttir, K; Kristjánsdóttir, K; Kjartansson, J; Ögmundsdóttir, H M; Rafnar, T

    2000-01-01

    Fas ligand (FasL) is expressed on some cancers and may play a role in the immune evasion of the tumour. We used immuno-histochemistry to study the expression of Fas and FasL in tissue samples from breast cancer patients, as well as normal breast tissue. Our results show that Fas and FasL are co-expressed both in normal tissue and in breast tumours. Fas and FasL mRNA were expressed in fresh normal and malignant breast tissue, as well as cultured breast epithelium and breast cancer cell lines. Flow cytometry analysis of live cells failed to detect FasL on the surface of normal or malignant breast cells; however, both stained positive for FasL after permeabilization. Fas was detected on the surface of normal breast cells and T47D and MCF-10A cell lines but only intracellularly in other breast cell lines tested. Neither normal breast epithelium nor breast cell lines induced Fas-dependent apoptosis in Jurkat cells. Finally, 20 tumour samples were stained for apoptosis. Few apoptotic cells were detected and there was no increase in apoptotic cells on the borders between tumour cells and lymphocytes. We conclude that FasL is expressed intracellularly in both normal and malignant breast epithelium and unlikely to be important for the immune evasion of breast tumours. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11104571

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

    SciTech Connect

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

    2014-10-01

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

  19. Variation in Langerhans cell number and morphology between the upper and lower regions of the human esophageal epithelium.

    PubMed

    Zavala, Walther D; De Simone, Dino Sanchez; Sacerdote, Fabio L; Cavicchia, Juan C

    2002-12-01

    Langerhans cells (LCs) are dendritic components of stratified epithelia, presenting antigens to other cells of the immune system that play a crucial role in local defense. The paucity of information about their significance in the esophageal mucosa was addressed by studying their distribution and morphology in this particular location. LCs were identified by immunohistochemical detection of CD1a, a cell-specific marker, using a monoclonal antibody, as well as by electron microscopic identification of characteristic Birbeck granules, among other typical morphological features. Cell counts carried out at 25 and 35 cm distal to the dental arch demonstrated significant differences in number and size between the two locations. The upper region contained 10.4 +/- 0.8 cells (mean +/- SEM) vs. 18.4 +/- 1.4 cells in the lower region. Also, cells in the lower region were larger and appeared to have longer dendritic processes. To our knowledge this is the first report of regional differences in number and morphology of LCs in human esophageal mucosa.

  20. Regulation of transepithelial ion transport and intracellular calcium by extracellular ATP in human normal and cystic fibrosis airway epithelium.

    PubMed Central

    Mason, S. J.; Paradiso, A. M.; Boucher, R. C.

    1991-01-01

    1 The role of extracellular nucleotides in regulation of ion transport activities (short circuit current, Isc) of human respiratory epithelia was studied. 2 Application of nucleotides to the apical or basolateral membrane of human nasal epithelium induced a concentration-dependent increase in Isc. 3 The rank order of potency of purine- or pyrimidine-induced changes in Isc of normal human nasal epithelium when applied to the apical membrane (UTP greater than or equal to ATP greater than ATP gamma S greater than 2MeSATP greater than ADP beta S much greater than beta gamma MeATP greater than or equal to alpha beta MeATP) or basolateral membrane (2MeSATP greater than UTP greater than ATP greater than ATP gamma S greater than alpha beta MeATP greater than beta gamma MeATP) is consistent with involvement of a P2 purinoceptor. A similar rank order of potencies was observed for nucleotide effects on intracellular calcium measured by Fura-2 fluorescence using microspectrofluorimetry. 4 Similar nucleotide potency in the regulation of ion transport and intracellular calcium in cystic fibrosis (CF) airway epithelium (UTP greater than or equal to ATP) was observed, suggesting purinoceptors might be used to stimulate ion transport processes that would promote hydration of airway secretions and facilitate their clearance from CF lungs. 5 These data provide evidence for the regulation of ion transport by P2 purinoceptors in normal and cystic fibrosis human airway epithelium. PMID:1718521

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

    SciTech Connect

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

    1986-03-01

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

  2. Abnormal esophageal transit in patients with typical reflux symptoms but normal endoscopic and pH profiles

    SciTech Connect

    Eriksen, C.A.; Cullen, P.T.; Sutton, D.; Kennedy, N.; Cuschieri, A. )

    1991-06-01

    There is a small, well-known cohort of patients who, despite classic reflux symptoms, have a normal esophageal pH profile and endoscopic picture. The treatment of these patients has proved problematic. In an attempt at determining the pathophysiology of this subgroup, the authors investigated the esophageal transit, using the radiolabeled solid bolus esophageal egg transit technique, in 58 such patients: 25 males, 33 females, mean age 39.5 years (range: 13 to 65 years). The egg transit was normal in 31 (53.4%) patients. In the remaining 27 (46.6%) patients, the condensed image analysis showed the following specific abnormal transit patterns: step delay pattern, demonstrating segmental hold-up in mid- or distal esophagus in 16 (59.3%); nonspecific delay in 6 (22.2%); oscillatory pattern in 3 (11.1%); and total nonclearance during the study period (4 minutes) in 2 (7.4%) patients. The patients with abnormal transit patterns had demographic parameters and symptom scores similar to those found in patients with normal transit. This study shows that almost 50% of patients with reflux symptoms and negative pH and endoscopy have abnormal esophageal transit, and almost two thirds of these patients display segmental transit delay in the lower half of the esophagus. The effect on symptomatology by prokinetic agents in the patient subgroup needs evaluation.

  3. Differences in expression of retinal pigment epithelium mRNA between normal canines

    PubMed Central

    2004-01-01

    Abstract A reference database of differences in mRNA expression in normal healthy canine retinal pigment epithelium (RPE) has been established. This database identifies non-informative differences in mRNA expression that can be used in screening canine RPE for mutations associated with clinical effects on vision. Complementary DNA (cDNA) pools were prepared from mRNA harvested from RPE, amplified by PCR, and used in a subtractive hybridization protocol (representational differential analysis) to identify differences in RPE mRNA expression between canines. The effect of relatedness of the test canines on the frequency of occurrence of differences was evaluated by using 2 unrelated canines for comparison with 2 female sibling canines of blue heeler/bull terrier lineage. Differentially expressed cDNA species were cloned, sequenced, and identified by comparison to public database entries. The most frequently observed differentially expressed sequence from the unrelated canine comparison was cDNA with 21 base pairs (bp) identical to the human epithelial membrane protein 1 gene (present in 8 of 20 clones). Different clones from the same-sex sibling RPE contained repetitions of several short sequence motifs including the human epithelial membrane protein 1 (4 of 25 clones). Other prevalent differences between sibling RPE included sequences similar to a chicken genetic marker sequence motif (5 of 25), and 6 clones with homology to porcine major histocompatibility loci. In addition to identifying several repetitively occurring, noninformative, differentially expressed RPE mRNA species, the findings confirm that fewer differences occurred between siblings, highlighting the importance of using closely related subjects in representational difference analysis studies. PMID:15352545

  4. Role of fucosyltransferases in the association between apomucin and Lewis antigen expression in normal and malignant gastric epithelium

    PubMed Central

    Lopez-Ferrer, A; de Bolos, C; Barranco, C; Garrido, M; Isern, J; Carlstedt, I; Reis, C; Torrado, J; Real, F

    2000-01-01

    BACKGROUND—In normal gastric epithelium, MUC5AC is detected in superficial epithelium associated with Lewis type 1 antigens and MUC6 is detected in antral glands with Lewis type 2. Therefore, the stomach constitutes an excellent model to examine the role of glycosyltransferases in determining the specificity of apomucin glycosylation.
AIMS—To determine the molecular basis of this association and to examine changes in expression of gastric and intestinal apomucins and their association with Lewis antigens during the gastric carcinogenesis process.
METHODS—Fucosyltransferase (FUT1, FUT2, FUT3) and mucin (MUC5AC, MUC6) transcripts were detected using reverse transcription-polymerase chain reaction. Apomucin (MUC2, MUC4, MUC5AC, MUC6) and Lewis antigen (types 1 and 2) expression were analysed using single and double immunohistochemistry and in situ hybridisation.
RESULTS—In the normal stomach, FUT1 is exclusively detected associated with MUC6; FUT2 is only detected when MUC5AC is present. This co-regulation is lost in gastric tumours, as is differential expression of MUC5AC and MUC6 in normal gastric epithelial cells. In gastric tumours, especially those with the intestinal phenotype, MUC2 and MUC4 genes are upregulated, and gastric-type and intestinal-type mucins are coexpressed. These changes are early events in the gastric carcinogenesis process, as they are detected in intestinal metaplasia.
CONCLUSIONS—The glycosylation pattern found in normal gastric epithelium is dictated by the specific set of fucosyltranferases expressed by the cells rather than by the apomucin sequence. The development of intestinal metaplasia and gastric cancer is associated with the appearance of cellular phenotypes that are absent from normal epithelium.


Keywords: fucosyltransferases; gastric carcinogenesis; gastric mucins; Lewis antigens PMID:10940270

  5. Influence of acid and bile acid on ERK activity, PPARγ expression and cell proliferation in normal human esophageal epithelial cells

    PubMed Central

    Jiang, Zhi-Ru; Gong, Jun; Zhang, Zhen-Ni; Qiao, Zhe

    2006-01-01

    AIM: To observe the effects of acid and bile acid exposure on cell proliferation and the expression of extracellular signal-regulated protein kinase (ERK) and peroxisome proliferator-activated receptor γ (PPARγ) in normal human esophageal epithelial cells in vitro. METHODS: In vitro cultured normal human esophageal epithelial cells were exposed to acidic media (pH 4.0 - 6.5), media containing different bile acid (250 μmol/L), media containing acid and bile acid, respectively. Cell proliferation was assessed using MTT and flow cytometry. The expressions of phosphorylated ERK1/2 and PPARγ protein were determined by the immunoblotting technique. RESULTS: Acid-exposed (3 min) esophageal cells exhibited a significant increase in proliferation ratio, S phase of the cell cycle (P < 0.05) and the level of phosphorylated ERK1/2 protein. When the acid-exposure period exceeded 6 min, we observed a decrease in proliferation ratio and S phase of the cell cycle, with an increased apoptosis ratio (P < 0.05). Bile acid exposure (3-12 min) also produced an increase in proliferation ratio, S phase of the cell cycle (P < 0.05) and phosphorylated ERK1/2 expression. On the contrary, deoxycholic acid (DCA) exposure (> 20 min) decreased proliferation ratio. Compared with bile acid exposure (pH 7.4), bile acid exposure (pH 6.5, 4) significantly decreased proliferation ratio (P < 0.05). There was no expression of PPARγ in normal human esophageal epithelial cells. CONCLUSION: The rapid stimuli of acid or bile acid increase proliferation in normal human esophageal epithelial cells by activating the ERK pathway. PMID:16688842

  6. [Telomerase activity in esophageal carcinoma and lesions unstained with Lugol's solution].

    PubMed

    Yoneyama, K; Aoyama, N; Koizumi, H; Tamai, S

    1998-05-01

    Telomerase is a specific enzyme required for the replication of telomeres. Its activity is detected in almost human cancers. We examined in esophageal carcinoma and lesions unstained with Lugol's solution telomerase activity by using telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was detected in all 22 esophageal carcinomas, regardless of histopathological findings. In unstained lesions, telomerase activity was detected in 15 of 22; 10 squamous cell carcinomas, four dysplasia, one regenerative epithelium, no telomerase activity was found in seven; four normal esophageal epithelia, two Barrett's esophagi, one regenerative epithelium. These results suggest that telomerase activity may be a useful molecular marker for the diagnosis of esophageal carcinoma and of the early esophageal carcinoma in area unstained with Lugol's solution.

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

    PubMed

    Ortega-Martínez, Marta; Rodríguez-Flores, Laura E; de-la-Garza-González, Carlos; Ancer-Rodríguez, Jesús; Jaramillo-Rangel, Gilberto

    2015-11-01

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

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

    PubMed Central

    2014-01-01

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

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

    SciTech Connect

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

    1982-08-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed Central

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

    2009-01-01

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

  12. Early changes of dog esophageal mucosa induced by N-ethyl-N'-nitro-N-nitrosoguanidine.

    PubMed

    Takubo, K; Shisa, H; Futatsuki, K; Sasajima, K

    1981-12-01

    Early changes in the esophageal mucosa of dogs induced by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) were studied. Seven one-year-old beagle dogs were given a solution of 250 micrograms ENNG/ml to drink ad libitum for 4 months. Three different kinds of lesions (10 erosive carcinomas, 4 slightly elevated microcarcinomas and 19 leukoplakias) were recognized. These three kinds of lesions were not located adjacent to one another, and were surrounded by almost normal stratified squamous epithelium. The foci of the carcinomas revealed an abrupt transition to normal epithelium and were considered to have arisen abruptly from normal esophageal epithelium. The histogenesis of squamous cell carcinomas of the esophagus in dogs may differ from that in man.

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

    PubMed Central

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

    2012-01-01

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

  14. Effect of hypoxia and TP53 mutation status and cytogenetics of normal and malignant mammary epithelium.

    PubMed

    Vidarsson, Hilmar; Steinarsdóttir, Margrét; Jónasson, Jón Gunnlaugur; Júlíusdóttir, Hildur; Hauksdóttir, Halla; Hilmarsdóttir, Hólmfrídur; Halldórsdóttir, Kristín; Ogmundsdóttir, Helga M

    2006-03-01

    It has been proposed that hypoxia favors the growth of tumor cells over normal cells, particularly tumor cells carrying TP53 mutations. Cytogenetic studies of breast cancer have shown that highly complex karyotypes seen in direct harvest preparations are rarely detected after short-term culture. In this study, 34 paired samples of breast carcinomas and grossly nontumorous tissue from the same breast were cultured at 20 and 5% (12 samples) or 20 and 0% oxygen (22 samples). Both carcinoma samples and nontumorous tissue survived at 0% oxygen. Recovery for 24 hours at 20% produced good yields for cytogenetic analysis. Lower oxygen levels did not specifically stimulate growth of tumor cells. Samples with TP53 mutations showed a consistently increased growth under anaerobic hypoxic conditions. Culture at 5% oxygen did not generally reveal more karyotypic abnormalities than found at 20%. In the samples cultured at 0 and 20%, karyotypic abnormalities were detected only in anaerobic hypoxic culture in two cases. Of the only four samples where more complex karyotypes were detected in the low-oxygen culture, two were TP53 mutated. Hypoxic treatment followed by recovery at 20% oxygen may thus increase the yield of complex karyotypes from a subset of breast carcinomas, particularly those with mutated TP53.

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

    PubMed Central

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

    2016-01-01

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

  16. Esophageal carcinoid tumor treated by endoscopic resection.

    PubMed

    Yagi, Makoto; Abe, Yasuhiko; Sasaki, Yu; Nomura, Eiki; Sato, Takeshi; Iwano, Daisuke; Yoshizawa, Kazuya; Sakuta, Kazuhiro; Kanno, Nana; Nishise, Syouichi; Ueno, Yoshiyuki

    2015-05-01

    The present report describes a rare case of esophageal carcinoid tumor that was treated by endoscopic resection. A 43-year-old woman underwent esophagogastroduodenoscopy at her family clinic for screening of the upper digestive tract and a small lesion resembling a submucosal tumor was detected in the lower esophagus. A biopsy sample from the lesion was diagnosed as esophageal carcinoid tumor and the patient visited our hospital for detailed examination. The tumor was approximately 3 mm in diameter and its surface appeared to be covered with normal squamous epithelium. The tumor had a shiny reddish surface without ulceration or erosion. Magnifying endoscopy with narrow-band imaging showed structures resembling reticular vessels under the epithelium. Endoscopic ultrasonography depicted the tumor as a low-echoic mass within the lamina propria. Computed tomography did not detect the tumor and no metastatic lesions were evident in other organs. With the patient's informed consent, the tumor was resected using endoscopic submucosal dissection, with a sufficient free margin in both the vertical and horizontal directions. Magnifying endoscopic examination showed the resected tumor to have abundant reticular vessels. Finally, the tumor was diagnosed immunopathologically as an esophageal carcinoid tumor (neuroendocrine cell tumor, grade 1), without lymphatic or vascular invasion.

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

    PubMed Central

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

    2015-01-01

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

  18. Gene expression profiles of estrogen receptor positive and estrogen receptor negative breast cancers are detectable in histologically normal breast epithelium

    PubMed Central

    Graham, Kelly; Ge, Xijin; de las Morenas, Antonio; Tripathi, Anusri; Rosenberg, Carol L.

    2010-01-01

    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. PMID:21059815

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Overholt, Bergein F.; Panjehpour, Masoud

    1995-03-01

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

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

    PubMed

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

    2016-05-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. From reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma

    PubMed Central

    Wang, Rui-Hua

    2015-01-01

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

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

    PubMed

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

    2012-06-01

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

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

    PubMed

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

    2015-07-01

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

  6. Esophageal scintigraphy: applications and limitations in the study of esophageal disorders.

    PubMed

    O'Connor, M K; Byrne, P J; Keeling, P; Hennessy, T P

    1988-01-01

    This study examines the scintigraphic transit pattern in a variety of esophageal disorders. Scintigraphy was performed with a semi solid bolus and the patient in an upright position. Condensed esophageal images were obtained from which we derived the esophageal transit time. The pattern of bolus transit was graded by the duration of transit and by the presence of hold up or retrograde motion. Scintigrams were performed in 11 volunteers and 88 patients whose esophageal function had been confirmed by conventional gastroesophageal techniques. Esophageal disorders examined included achalasia (20), scleroderma (9), esophageal carcinoma (8), Barrett esophagus (5), and reflux esophagitis (27). We also examined the effects of gastroesophageal surgery on esophageal function. Transit times distinguished grossly abnormal esophageal function from normal but did not distinguish between different esophageal disorders. Graded transit patterns were a more sensitive indicator of esophageal function and permitted some differentiation between esophageal disorders and allowed evaluation of the effects of gastroesophageal surgery.

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

    NASA Astrophysics Data System (ADS)

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

    2011-02-01

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

  8. Eosinophilic esophagitis: Update in diagnosis and management. Position paper by the Italian Society of Gastroenterology and Gastrointestinal Endoscopy (SIGE).

    PubMed

    de Bortoli, Nicola; Penagini, Roberto; Savarino, Edoardo; Marchi, Santino

    2017-03-01

    Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease of the esophagus characterized by symptoms related to esophageal dysfunction, as well as significant esophageal eosinophilia. The entity exists worldwide but has been most extensively studied in Western countries. However, a wide range of symptoms has been noticed such as chest pain or gastro-esophageal reflux disease-like symptoms. Upper gastro-intestinal endoscopy and esophageal biopsies are crucial for the diagnosis. Endoscopy might be normal or reveal typical patterns such as rings, furrows, exudates, edema, and stricture. Two to four biopsies should be performed both in the distal and in the proximal esophagus, and 15 eosinophils per high power field within the esophageal epithelium are the minimal threshold to diagnose eosinophilic esophagitis. Allergy testing is recommended, although its impact to orient treatment remains to be demonstrated. Eosinophilic esophagitis treatment includes medical treatment, diet and endoscopic dilation. Proton pump inhibitors are the first-line therapy as up to 50% of patients respond well to proton pump inhibitors irrespective of objective evidence of GERD. Topical viscous corticosteroids or elimination diet are the treatment of choice in case of unresponsiveness to proton pump inhibitors.

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

    PubMed Central

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

    2016-01-01

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

  10. Variations of mitotic index in normal and dysplastic squamous epithelium of the uterine cervix as a function of endometrial maturation.

    PubMed

    Fadare, Oluwole; Yi, Xiaofang; Liang, Sharon X; Ma, Yanling; Zheng, Wenxin

    2007-09-01

    that hormonal status, as reflected in endometrial maturation, can significantly affect the mitotic index of dysplastic squamous epithelium of the uterine cervix. Our findings confirm that the pathologic grading of dysplasia, especially in equivocal cases such as in metaplastic squamous epithelium, should not be solely dependent on the finding mitoses in the cervical squamous epithelium. The full composite of histopathologic features should form the basis for this determination.

  11. A case of exfoliative esophagitis with pemphigus vulgaris.

    PubMed

    Fukuchi, M; Otake, S; Naitoh, H; Shoji, H; Yamagishi, J; Suzuki, M; Yanoma, T; Kuwano, H

    2011-04-01

    Autoimmune blistering skin diseases, including pemphigus vulgaris, rarely involve the esophagus. We report a case of exfoliative esophagitis with pemphigus vulgaris. A sloughing esophageal cast observed by endoscopy was dissected esophageal squamous epithelium in all layers. Our case is the fifth case of pemphigus vulgaris associated with esophageal cast formation recorded in the medical literature. Prednisolone was administered, and both the pemphigus vulgaris and exfoliative esophagitis improved. Upon findings of exfoliative esophagitis by endoscopic examination, we should consider the coexistence of blistering skin diseases, including pemphigus vulgaris.

  12. Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

    PubMed

    Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

    2017-03-16

    We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

  13. Functional Esophageal Disorders.

    PubMed

    Aziz, Qasim; Fass, Ronnie; Gyawali, C Prakash; Miwa, Hiroto; Pandolfino, John E; Zerbib, Frank

    2016-02-15

    Functional esophageal disorders consist of a disease category that present with esophageal symptoms (heartburn, chest pain, dysphagia, globus) not explained by mechanical obstruction (stricture, tumor, eosinophilic esophagitis), major motor disorders (achalasia, EGJ outflow obstruction, absent contractility, distal esophageal spasm, jackhammer esophagus), or gastroesophageal reflux disease (GERD). While mechanisms responsible are unclear, it is theorized that visceral hypersensitivity and hypervigilance play an important role in symptom generation, in the context of normal or borderline function. Treatments directed at improving borderline motor dysfunction or reducing reflux burden to sub-normal levels have limited success in symptom improvement. In contrast, strategies focused on modulating peripheral triggering and central perception are mechanistically viable and clinically meaningful. However, outcome data from these treatment options are limited. Future research needs to focus on understanding mechanisms underlying visceral hypersensitivity and hypervigilance so that appropriate targets and therapies can be developed.

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

    SciTech Connect

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

    2011-12-01

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

  15. Esophageal Cancer

    MedlinePlus

    ... from your throat to your stomach. Early esophageal cancer usually does not cause symptoms. Later, you may ... You're at greater risk for getting esophageal cancer if you smoke, drink heavily, or have acid ...

  16. Esophageal cancer

    MedlinePlus

    Cancer - esophagus ... Esophageal cancer is not common in the United States. It occurs most often in men over 50 years old. There are two main types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. These two types ...

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

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

    1994-11-28

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

  19. Quantitation of TGF-β proteins in mouse tissues shows reciprocal changes in TGF-β1 and TGF-β3 in normal vs neoplastic mammary epithelium.

    PubMed

    Flanders, Kathleen C; Yang, Yu-An; Herrmann, Michelle; Chen, JinQiu; Mendoza, Nerissa; Mirza, Amer M; Wakefield, Lalage M

    2016-06-21

    Transforming growth factor-βs (TGF-βs) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-β1, -β2, and -β3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-β isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex® xMAP®-based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF-β1 is the predominant isoform with TGF-β2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-β2. The only adult tissue expressing appreciable TGF-β3 was the mammary gland, where its levels were comparable to TGF-β1. In situ hybridization showed the luminal epithelium as the major source of all TGF-β isoforms in the normal mammary gland. TGF-β1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-β3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis.

  20. Quantitation of TGF-β proteins in mouse tissues shows reciprocal changes in TGF-β1 and TGF-β3 in normal vs neoplastic mammary epithelium

    PubMed Central

    Herrmann, Michelle; Chen, JinQiu; Mendoza, Nerissa; Mirza, Amer M.; Wakefield, Lalage M.

    2016-01-01

    Transforming growth factor-βs (TGF-βs) regulate tissue homeostasis, and their expression is perturbed in many diseases. The three isoforms (TGF-β1, -β2, and -β3) have similar bioactivities in vitro but show distinct activities in vivo. Little quantitative information exists for expression of TGF-β isoform proteins in physiology or disease. We developed an optimized method to quantitate protein levels of the three isoforms, using a Luminex® xMAP®-based multianalyte assay following acid-ethanol extraction of tissues. Analysis of multiple tissues and plasma from four strains of adult mice showed that TGF-β1 is the predominant isoform with TGF-β2 being ~10-fold lower. There were no sex-specific differences in isoform expression, but some tissues showed inter-strain variation, particularly for TGF-β2. The only adult tissue expressing appreciable TGF-β3 was the mammary gland, where its levels were comparable to TGF-β1. In situ hybridization showed the luminal epithelium as the major source of all TGF-β isoforms in the normal mammary gland. TGF-β1 protein was 3-8-fold higher in three murine mammary tumor models than in normal mammary gland, while TGF-β3 protein was 2-3-fold lower in tumors than normal tissue, suggesting reciprocal regulation of these isoforms in mammary tumorigenesis. PMID:27203217

  1. Deoxycholic acid impairs glycosylation and fucosylation processes in esophageal epithelial cells.

    PubMed

    Byrne, Anne-Marie; Sharma, Ruchika; Duggan, Gina; Kelleher, Dermot; Long, Aideen

    2012-05-01

    It is generally accepted that esophageal adenocarcinoma arises from a Barrett's metaplastic lesion. Altered glycoprotein expression has been demonstrated in tissue from patients with Barrett's esophagus and esophageal cancer but the mechanisms regarding such changes are unknown. The bile acid deoxycholic acid (DCA) alters many cell signaling pathways and is implicated in esophageal cancer progression. We have demonstrated that DCA disrupts Golgi structure and affects protein secretion and glycosylation processes in cell lines derived from normal squamous epithelium (HET-1A) and Barrett's metaplastic epithelium (QH). Cell surface expression of glycans was identified using carbohydrate-specific probes (wheat germ agglutinate, conconavalin A, peanut agglutinin, lithocholic acid and Ulex europaeus agglutinin) that monitored N-glycosylation, O-glycosylation and core fucosylation in resting and DCA-treated cells. DCA altered intracellular localization and reduced cell surface expression of N-acetyl-D-glucosamine, α-methyl-mannopyranoside (Man/Glc) and fucose in both cell lines. Furthermore, DCA reduced the expression of epithelial growth factor receptor and E-cadherin in a manner analogous to treatment of cells with the N-glycan biosynthesis inhibitor tunicamycin. This is the first study to identify an altered Golgi structure and glycomic profile in response to DCA in esophageal epithelial cells, a process which could potentially contribute to metaplasia, dysplasia and cancer of the esophagus.

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

    PubMed

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

    2016-01-01

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

  3. Esophageal motility disorders in HIV patients.

    PubMed

    Zalar, Alberto E; Olmos, Martín A; Piskorz, Eduardo L; Magnanini, Fernando L

    2003-05-01

    Opportunistic esophageal infections (Candida, cytomegalovirus, herpes simplex virus) and idiophatic esophageal ulcerations are commonly found in HIV patients. However, motility disorders of the esophagus have seldom been investigated in this population. The aim of this prospective study was to determine the presence of motility disorders in HIV patients with esophageal symptoms (with or without associated lesions detected by endoscopy) and in HIV patients without esophageal symptoms and normal esophagoscopy. Eigthteen consecutive HIV patients (10 male, 8 female, ages 20-44 years, mean age 33.5; 8 HIV positive and 10 AIDS) were studied prospectively. Nine patients complained of esophageal symptoms, e.g, dysphagia/odynophagia (group 1) and 9 had symptoms not related to esophageal disease, such as diarrhea, abdominal pain, or gastrointestinal bleeding (group 2). All patients underwent upper endoscopy; mucosal biopsies were taken when macroscopic esophageal lesions were identified or when the patients were symptomatic even if the esophageal mucosa was normal. Esophageal manometry was performed in the 18 patients, using a 4-channel water-perfused system according to a standardized technique. Sixteen of the 18 patients (88.8%) had baseline manometric abnormalities. In group 1, 8/9 patients had esophageal motility disorders: nutcrackeresophagus in 1, hypertensive lower esophageal sphincter (LES) with incomplete relaxation in 2, nonspecific esophageal motility disorders (NEMD) in 3, diffuse esophageal spasm in 1, esophageal hypocontraction with low LES pressure in 1. Six of these 9 patients had lesions detected by endoscopy: CMV ulcers in 2, idiopathic ulcers in 1, candidiasis in 1, idiopathic ulcer + candidiasis in 1, nonspecific esophagitis in 1; and 3/9 had normal endoscopy and normal esophageal biopsies. In group 2, 8/9 patients had abnormal motility: hypertensive LES with incomplete relaxation in 1, nutcracker esophagus in 2, esophageal hypocontraction in 3, and NEMD

  4. Esophageal epiphrenic diverticulum associated with diffuse esophageal spasm

    PubMed Central

    Matsumoto, Hideo; Kubota, Hisako; Higashida, Masaharu; Manabe, Noriaki; Haruma, Ken; Hirai, Toshihiro

    2015-01-01

    Introduction Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. Presentation of case We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right-sided esophageal diverticulum located about 10 cm above the esophagogastric junction. High-resolution manometry revealed normal esophageal motility. However, 24-h pH monitoring revealed continuous acidity due to pooling of residue in the diverticulum. An esophageal epiphrenic diverticulum was diagnosed and resected thoracoscopically. Her dysphagia recurred 2 years later. High-resolution manometry revealed diffuse esophageal spasm. Discussion The diverticulum in the present case was considered to have been associated with diffuse esophageal spasm. The motility disorder was likely not identified at the first evaluation. Conclusion In this case, the patient’s symptoms spontaneously resolved without any treatment; however, longer-term follow-up is needed. PMID:26143577

  5. Spatial differentiation of the intestinal epithelium: analysis of enteroendocrine cells containing immunoreactive serotonin, secretin, and substance P in normal and transgenic mice.

    PubMed Central

    Roth, K A; Gordon, J I

    1990-01-01

    The mammalian intestinal epithelium undergoes continuous and rapid renewal of its four principal terminally differentiated cell types. These cells arise from multipotent stem cells located at or near the base of the crypts of Lieberkühn. The differentiation process is precisely organized along two spatial dimensions (axes)--from the crypt to the villus tip and from the duodenum to the colon. The enteroendocrine cell population provides a sensitive marker of the intestine's topologic differentiation. At least 15 different regionally distributed subsets have been described based on their principal neuroendocrine products. We have used immunocytochemical methods to characterize the spatial relationships of the serotonin-, secretin-, and substance P-containing enteroendocrine cell subsets in normal adult C57BL/6J x LT/Sv mice as well as in transgenic littermates that contain rat liver fatty acid-binding protein-human growth hormone fusion genes. Our results reveal precise spatial interrelationships between these populations and suggest a differentiation pathway that may involve the sequential expression of substance P, serotonin, and secretin. Images PMID:1696730

  6. Selection of internal reference genes for normalization of reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis in the rumen epithelium

    PubMed Central

    Die, Jose V.; Rowland, Lisa J.; Li, Robert; Oh, Sunghee; Li, Congjun; Connor, Erin E.; Ranilla, Maria-Jose

    2017-01-01

    The rumen is lined on the luminal side by a stratified squamous epithelium that is responsible for not only absorption, but also transport, extensive short-chain fatty acid (SCFA) metabolism and protection. Butyrate has been demonstrated to initiate the differentiation of the tissue following introduction of solid feed to the weaning neonate as well as affecting the metabolism of other nutrients and absorption of nutrients in in vitro experiments. The objective of the present study was to validate expression stability of eight putative reference genes bovine rumen, considering the intrinsic heterogeneity of bovine rumen with regard to different luminal characteristics due to direct infusion of butyrate to double the intra-ruminal content of the rumen liquor. Our focus was on identifying stable reference genes which are suitable to normalize real-time RT-qPCR experiments from rumen samples collected from clinical assays, irrespective of localization within the organ and the across physiological state. The most stably expressed genes included: ACTB, UXT, DBNDD2, RPS9, DDX54 and HMBS. Their high stability values suggest these reference genes will facilitate better evaluation of variation of across an array of conditions including: localization within the rumen, differences among cattle fed an array of rations, as well as response to development in the weaning animal. Moreover, we anticipate these reference genes may be useful for expression studies in other ruminants. PMID:28234977

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

    PubMed

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

    2015-12-01

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

  8. Esophagitis - infectious

    MedlinePlus

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

  9. The morphology and kinetics of spermatogonial degeneration in normal adult rats: an analysis using a simplified classification of the germinal epithelium.

    PubMed

    Huckins, C

    1978-04-01

    normal generminal epithelium remain obscure, it is proposed that the numerical ratio of A spermatogonia to Sertoli cells may be a significant limiting factor.

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

    PubMed

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

    2008-01-01

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

  11. Esophageal cancer.

    PubMed

    Vakil, Nimish; Affi, Aboud

    2002-07-01

    Despite advances in our knowledge of esophageal cancer, 50% of patients present with incurable disease, and the overall survival after diagnosis is poor. The incidence of esophageal adenocarcinoma of the distal esophagus is rising at a rapid rate in developed countries. Recent advances in the epidemiology of esophageal cancer offer insights into preventive strategies in patients who are at risk. New developments in diagnosis may help detect the disease at an early stage. New diagnostic modalities permit more accurate staging procedures and allow appropriate selection of therapy. New studies provide more information on multimodality therapy for esophageal cancer, and new endoscopic techniques allow resection of small lesions without surgery. New stent designs provide better palliation by providing tumor ingrowth. These developments in the treatment of esophageal cancer are the focus of this review.

  12. Characterization of Barrett esophagus and esophageal adenocarcinoma by Fourier-transform infrared microscopy.

    PubMed

    Quaroni, Luca; Casson, Alan G

    2009-06-01

    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.

  13. The pathophysiology of eosinophilic esophagitis.

    PubMed

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

    2014-01-01

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

  14. Morphofunctional analysis of experimental model of esophageal achalasia in rats.

    PubMed

    Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

    2010-10-01

    We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

  15. Esophageal Cancer

    MedlinePlus

    ... cancer is found, the better the chance of recovery; however, esophageal cancer is often found at an ... has decreased, the tubes will be removed. Recovery Recovery As with any surgery or operation, there are ...

  16. Esophageal atresia

    MedlinePlus

    Esophageal atresia (EA) is a congenital defect. This means it occurs before birth. There are several types. In most cases, the ... the lower esophagus and stomach. Most infants with EA have another defect called tracheoesophageal fistula (TEF). This ...

  17. Eosinophilic esophagitis

    PubMed Central

    Dellon, Evan S.

    2012-01-01

    Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition where infiltration of eosinophils into the esophageal mucosa leads to symptoms of esophageal dysfunction. It has rapidly emerged as an important cause of upper GI morbidity in patients of all ages and is encountered in a substantial proportion of patients undergoing diagnostic upper endoscopy. This review discusses the clinical, endoscopic, and histologic features of EoE and presents the most recent guidelines for diagnosis of EoE. It describes selected diagnostic dilemmas including distinguishing EoE from gastroesophageal reflux disease and addressing the newly recognized clinical entity of proton pump inhibitor responsive esophageal eosinophilia. It also highlights evidence to support both pharmacologic and non-pharmacologic treatments, including topical corticosteroids, dietary elimination therapy, and endoscopic dilation. PMID:23452635

  18. Esophageal Cancer

    MedlinePlus

    ... is the sixth most common cause of cancer deaths worldwide. Incidence rates vary within different geographic locations. In some regions, higher rates of esophageal cancer cases may be attributed to tobacco and alcohol use or particular nutritional habits and ...

  19. Esophageal culture

    MedlinePlus

    Culture - esophageal ... There, it is placed in a special dish (culture) and watched for the growth of bacteria, fungi, ... and Fordtran's Gastrointestinal and Liver Disease Pathophysiology/Diagnosis/Management . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  20. Esophageal spasm

    MedlinePlus

    Kahrilas PJ, Pandolfino JE. Esophageal neuromuscular function and motility disorders. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease . 9th ed. Philadelphia, PA: ...

  1. Esophageal manometry

    MedlinePlus

    ... its ability to move food toward the stomach ( achalasia ) A weak LES, which causes heartburn (GERD) Abnormal ... PA: Elsevier Saunders; 2010:chap 43. Read More Achalasia Esophageal spasm Gastroesophageal reflux disease Review Date 8/ ...

  2. The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid.

    PubMed

    Roesly, Heather B; Khan, Mohammad R; Chen, Hwu Dau Rw; Hill, Kimberly A; Narendran, Nirushan; Watts, George S; Chen, Xiaoxin; Dvorak, Katerina

    2012-04-15

    Beclin-1 has a central role in the regulation of autophagy. Barrett's esophagus (BE) is associated with a significantly increased risk for the development of esophageal adenocarcinoma (EAC). In the current study, we evaluated the role of Beclin-1 and autophagy in the EAC. Biopsies obtained from patients with BE and EAC, tissues from a rat model of BE and EAC, and esophageal cell lines were evaluated for the expression of Beclin-1 by immunohistochemistry, immunoblotting, or RT-PCR. Since reflux of bile acids is important in EAC, we also evaluated the effect of exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression. Beclin-1 expression was high in squamous epithelium and nondysplastic BE, whereas its expression was low in dysplastic BE and EAC. The same pattern of expression was observed in rat tissues and in esophageal cell lines. Normal esophageal epithelium and HET-1A cells (derived from normal squamous epithelium) show high levels of Beclin-1, but lower levels of Beclin-1 were found in BE and EAC cell lines (CP-A, CP-C, and OE33). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy as evaluated by electron microscopy and counting percentage of GFP-LC3-positive BE cells with punctate pattern. In contrast, chronic exposure to DCA did not result in the alteration of Beclin-1 levels or autophagy. In summary, these data suggest that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance.

  3. Esophageal hypermotility: cause or effect?

    PubMed

    Crespin, O M; Tatum, R P; Yates, R B; Sahin, M; Coskun, K; Martin, A V; Wright, A; Oelschlager, B K; Pellegrini, C A

    2016-07-01

    . Postoperatively, all 38 patients had normal distal esophageal acid exposure. Of these 38 patients, symptoms resolved in 28 and improved in 10. Of six patients (one with NE, two JHE, and three with HTLES) that underwent postoperative esophageal manometry, five exhibited normal motility. Typical reflux symptoms are common among patients with esophageal hypermotility disorders. Abnormal 24-hour pH monitoring is present in the majority of patients with who report typical reflux symptoms and almost half of patients who report respiratory symptoms. Conversely, the majority of patients who report dysphagia or chest pain have normal distal esophageal acid exposure. Based on a small number of patients in this study, it also appears that motility disorders often improve after LNF. LNF is associated with resolution or improvement in reflux related symptoms and esophageal motility parameters in patients exhibiting abnormal esophageal acid exposure. This suggests that patient symptoms are due to abnormal acid exposure and not the motility disorder.

  4. Esophageal carcinogenesis in the rat: zinc deficiency, DNA methylation and alkyltransferase activity.

    PubMed

    Newberne, P M; Broitman, S; Schrager, T F

    1997-01-01

    Rats fed zinc-deficient diets and given an esophageal carcinogen, methylbenzylnitrosamine, develop tumors in greater incidence and with increased frequency compared to zinc-supplemented rats. This greater susceptibility is associated with a unique esophageal lesion, parakeratosis, with markedly increased epithelial necrosis and cell proliferation. Recent studies have shown that the increased susceptibility to tumorigenesis was further associated with a number of metabolic and biochemical alterations including increased binding of the carcinogen to DNA, shifts in O6-methylguanine (O6MeG)/7-methylguanine ratios and suggestions that the promutagen O6MeG lesion is not repaired effectively in the zinc-deficient esophagus; the latter was not reflected in the amount of O6-methyltransferase activity, however. The weight of evidence supports a presumption that zinc deficiency interferes with normal DNA repair mechanisms, the nature of which is not clear. An interesting additional finding was that zinc deficiency alone was associated with esophageal tumor induction, without carcinogen, which indicates that genetic material in the zinc-deficient esophageal epithelium is damaged sufficiently, without further chemical injury, to result in loss of control of cell proliferation. Manipulation of the time of exposure to zinc deficiency and carcinogen exposure defined the initiation period as most affected by the deficiency. Furthermore, reduced carcinogen exposure (and less toxicity), along with zinc deficiency, permits development of more tumors of the endophytic type, the form more relevant to human esophageal tumors. The groundwork, as described in this paper, has now been prepared to directly address the latter issue, endophytic tumors, and the putative relation of zinc deficiency to esophageal cancer in human populations.

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

    PubMed

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

    2016-12-01

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

  6. Role of Stroma-Derived Extracellular Matrix in Regulation of Growth and Hormonal Responsiveness of Normal and Cancerous Human Breast Epithelium.

    DTIC Science & Technology

    1998-09-01

    by residual estrogen or more likely by growth factor pathways ( Ignar -Trowbridge et al., 1996), have masked estrogen-induced proliferation in serum...an ERE- CAT construct independent of estrogen, but this was blocked by the anti-estrogen ICI 164,384 ( Ignar -Trowbridge et al., 1996). Again, these...modulates hormonal responsiveness of mammary epithelium in vivo in the mouse. Endocrinology, 129:2017-2023. Ignar -Trowbridge, D.M., M. Pimentel, M.G

  7. Esophageal transection

    PubMed Central

    Özçınar, Beyza; Peker, Kıvanç Derya; Demirel, Sertaç; Yanar, Fatih; Tuncer, Koray; İğci, Abdullah

    2016-01-01

    Herein, a case of intramural esophageal dissection is reported and the literature is reviewed. Intramural esophageal dissection is a rare but well described condition that is characterized by a laceration between the esophageal mucosa and submucosa but without perforation. A female patient aged 86 years was hospitalized with a diagnosis of abdominal aortic aneurysm. After placement of an aortic stent, she was started on intravenous heparin. After the procedure, the patient had retching and vomiting due to sedative drugs. On the first day after the procedure, the patient experienced sudden-onset chest pain, hematemesis, back pain and odynophagia. A hematoma was detected in the thoracic esophagus, which was opened during endoscopy and began to bleed suddenly owing to air insufflation. A false lumen was visualized within the esophagus. There was no perforation. The patient was followed up conservatively and discharged from the hospital uneventfully. In conclusion, we propose that esophageal transection, a condition that is widely regarded as relatively benign in the literature, has the potential to lead to perforation. It would be expected that most cases of esophageal transection would be managed conservatively. PMID:28149126

  8. Esophageal anastomosis.

    PubMed

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

    2015-01-01

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

  9. [Are loss of glistening of normal colour and increased friability normal aspects of the oesophagus in old age? (author's transl)].

    PubMed

    Leu, H; Schüle, A; Brändli, H; Pelloni, S; Blum, L

    1978-07-01

    Friability of the esophageal mucosq increases with old age. Old patients without esophageal disease also show loss of glistening and of the normal pink color of the mucosa. These findings on their own are therefore no signs of esophagitis,

  10. Immunohistochemical characterization of FHIT expression in normal human tissues

    PubMed Central

    Kujan, Omar; Abuderman, Abdulwahab; Al-Shawaf, Ahmad Zahi

    2016-01-01

    Background Fragile histidine triad (FHIT) is a tumor suppressor gene that is commonly inactivated in human tumors. Interestingly, the normal pattern of FHIT expression is largely unknown. Aim This study is aimed to characterize the expression of FHIT protein in normal human tissues. Materials and methods A total of 119 normal human tissue specimens were analyzed for the FHIT expression using immunohistochemistry technique. The inclusion criteria included: normal/inflammatory tissue with no evidence of cellular atypia. Results All studied specimens were stained positively with FHIT and showed either nuclear or cytoplasmic expression. Interestingly, the pattern of FHIT staining was similar among different specimens from each organ. FHIT is located predominantly in the nucleus, although cytoplasmic staining is also present in some cell types. Oral squamous epithelium, breast ductal epithelium, squamous and tubal metaplastic epithelium of the uterine cervix, esophageal squamous epithelium, salivary glands, and bronchial epithelia all strongly expressed the nuclear protein. In connective tissue, FHIT has shown strong cytoplasmic expression in histocytes including macrophages and dendritic cells, fibroblasts, and myofibroblasts. Conclusion Documentation of the pattern of FHIT expression in normal tissues will contribute to our understanding of the normal function of this protein and to interpretation of potentially altered FHIT expression in human tumors. PMID:28250975

  11. Pediatric esophageal scintigraphy. Results of 200 studies

    SciTech Connect

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

    1983-09-01

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

  12. Eosinophilic esophagitis

    PubMed Central

    Gupte, Anand R; Draganov, Peter V

    2009-01-01

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

  13. Radionuclide Esophageal Transit Scintigraphy in Primary Hypothyroidism

    PubMed Central

    Khan, Shoukat H; Madhu, Vijay P; Rather, Tanveer A; Laway, Bashir A

    2017-01-01

    Background/Aims Esophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in patients of primary hypothyroidism using the technique of radionuclide esophageal transit scintigraphy. Methods Thirty-one patients of primary hypothyroidism and 15 euthyroid healthy controls were evaluated for esophageal transit time using 15–20 MBq of Technetium-99m sulfur colloid diluted in 10–15 mL of drinking water. Time activity curve was generated for each study and esophageal transit time was calculated as time taken for clearance of 90% radioactive bolus from the region of interest encompassing the esophagus. Esophageal transit time of more than 10 seconds was considered as prolonged. Results Patients of primary hypothyroidism had a significantly increased mean esophageal transit time of 19.35 ± 20.02 seconds in comparison to the mean time of 8.25 ± 1.71 seconds in healthy controls (P < 0.05). Esophageal transit time improved and in some patients even normalized after treatment with thyroxine. A positive correlation (r = 0.39, P < 0.05) albeit weak existed between the serum thyroid stimulating hormone and the observed esophageal transit time. Conclusions A significant number of patients with primary hypothyroidism may have subclinical esophageal dysmotility with prolonged esophageal transit time which can be reversible by thyroxine treatment. Prolonged esophageal transit time in primary hypothyroidism may correlate with serum thyroid stimulating hormone levels. PMID:27444283

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

    PubMed

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

    2006-11-01

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

  15. Candida Esophagitis Incidentally Detected by 18F-FDG PET/CT in Metastatic Lung Adenocarcinoma

    PubMed Central

    Martínez-Amador, N; Martínez-Rodríguez, I; Quirce, R; Jiménez-Bonilla, J; Banzo, I

    2017-01-01

    The diagnostic significance of esophageal 18F-FDG uptake in oncologic patient is challenging. It may represent normal physiological uptake, inflammation, infection, or neoplasia. We present a patient with a recent diagnosis of non-small cell lung cancer stage IV and esophageal mild uptake on 18F-FDG PET/CT scan. Biopsy of esophageal mucosa demonstrated Candida esophagitis.

  16. Fundoplication improves disordered esophageal motility.

    PubMed

    Heider, T Ryan; Behrns, Kevin E; Koruda, Mark J; Shaheen, Nicholas J; Lucktong, Tananchai A; Bradshaw, Barbara; Farrell, Timothy M

    2003-02-01

    Patients with gastroesophageal reflux disease (GERD) and disordered esophageal motility are at risk for postoperative dysphagia, and are often treated with partial (270-degree) fundoplication as a strategy to minimize postoperative swallowing difficulties. Complete (360-degree) fundoplication, however, may provide more effective and durable reflux protection over time. Recently we reported that postfundoplication dysphagia is uncommon, regardless of preoperative manometric status and type of fundoplication. To determine whether esophageal function improves after fundoplication, we measured postoperative motility in patients in whom disordered esophageal motility had been documented before fundoplication. Forty-eight of 262 patients who underwent laparoscopic fundoplication between 1995 and 2000 satisfied preoperative manometric criteria for disordered esophageal motility (distal esophageal peristaltic amplitude < or =30 mm Hg and/or peristaltic frequency < or =80%). Of these, 19 had preoperative manometric assessment at our facility and consented to repeat study. Fifteen (79%) of these patients had a complete fundoplication and four (21%) had a partial fundoplication. Each patient underwent repeat four-channel esophageal manometry 29.5 +/- 18.4 months (mean +/- SD) after fundoplication. Distal esophageal peristaltic amplitude and peristaltic frequency were compared to preoperative data by paired t test. After fundoplication, mean peristaltic amplitude in the distal esophagus increased by 47% (56.8 +/- 30.9 mm Hg to 83.5 +/- 36.5 mm Hg; P < 0.001) and peristaltic frequency improved by 33% (66.4 +/- 28.7% to 87.6 +/- 16.3%; P < 0.01). Normal esophageal motor function was present in 14 patients (74%) after fundoplication, whereas in five patients the esophageal motor function remained abnormal (2 improved, 1 worsened, and 2 remained unchanged). Three patients with preoperative peristaltic frequencies of 0%, 10%, and 20% improved to 84%, 88%, and 50%, respectively

  17. Cytochrome P450 1B1 expression in rat esophageal tumorigenesis promoted by gastric and duodenal reflux.

    PubMed

    Devlin, Andrea H; McIlroy, Marie; McKeen, Hayley D; Bonde, Pramode; Menezes, A A Carlos; Swarbrick, Christine J; Robson, Tracy; Hirst, David G; Campbell, F Charles; McGuigan, James A; McKeown, Stephanie R

    2009-02-01

    Cytochrome P450 1B1 (CYP1B1) mRNA is constitutively expressed in most normal extra-hepatic tissues; however the protein is not detectable in these tissues but is expressed in a wide variety of tumors. CYP1B1 is responsible for the activation of a number of carcinogens present in tobacco smoke and food. A surgical model of rat esophageal tumorigenesis, promoted by gastric or duodenal reflux was used to determine CYP1B1 expression in premalignant esophageal tissue. Immunohistochemistry was performed using a modified amplified fluorescein tyramide protocol. CYP1B1 was not observed in normal esophageal mucosa, submucosa, or muscularis mucosa. Animals exposed to gastric reflux developed mild hyperplasia. Varying degrees of hyperplasia were observed in the duodenal reflux group. All regions of hyperplasia showed moderate or strong CYP1B1 immunoreactivity. Duodenal reflux induced a small number of premalignant changes: immunoreactivity was absent from the epithelium of squamous dysplasia (0/10), Barrett's esophagus (0/7), and majority of dysplastic Barrett's esophagus (1/4). Moderate or strong immunoreactivity was observed in the majority (7/8) of squamous cell carcinomas (SCCs) in situ. Immunoreactivity was also observed in the lamina propria and submucosa in association with inflammation, regardless of the severity of inflammation. The expression of CYP1B1 in hyperplasia, SCCs in situ, or in association with inflammation may increase the production of carcinogenic metabolites, which may promote esophageal tumorigenesis.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

  20. Cytoplasmic beta-catenin in esophageal cancers.

    PubMed

    Kimura, Y; Shiozaki, H; Doki, Y; Yamamoto, M; Utsunomiya, T; Kawanishi, K; Fukuchi, N; Inoue, M; Tsujinaka, T; Monden, M

    1999-04-20

    beta-Catenin has 2 distinct roles in E-cadherin-mediated cell adhesion and carcinogenesis through APC gene mutation. One occurs at cell-adhesion sites, where cadherins become linked to the actin-based cytoskeleton. The others occur in the cytoplasm and nuclei and are thought to regulate cell transformation. We studied these different beta-catenins and evaluated their significance in carcinogenesis. Fresh surgical specimens were obtained from 22 patients with squamous-cell carcinoma of the esophagus. beta-Catenin in the free soluble fraction and the insoluble fraction was immunoblotted separately. At the same time, its localization was observed by immuno-histochemical techniques. In the normal esophageal epithelium, 91% of beta-catenin was detected in the insoluble fraction and beta-catenin staining occurred at the cell membrane, in co-existence with E-cadherin. In cancerous tissues, the amount of soluble beta-catenin was significantly (about 4-fold) higher than in normal tissues. Also, in cancerous tissues with higher amounts of soluble beta-catenin, immuno-histochemical techniques revealed the presence of beta-catenin in the cytoplasm and nuclei, as well as in the cell membrane. However, in samples with lower amounts of beta-catenin, expression was found only at the cell boundaries. The amount of soluble beta-catenin was not associated with the clinico-pathological grading of the tumors. Our results show that the accumulation of free soluble beta-catenin in the cytoplasm and nuclei frequently occurs during carcinogenesis of the squamous epithelium of the esophagus.

  1. 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.

    PubMed

    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

    2007-11-01

    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

  2. Herpetic esophagitis (image)

    MedlinePlus

    Herpetic esophagitis is a herpes simplex infection causing inflammation and ulcers of the esophagus. Symptoms include difficulty swallowing and pain (dysphagia). Herpetic esophagitis can be effectively ...

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  5. Apoptosis and the Airway Epithelium

    PubMed Central

    White, Steven R.

    2011-01-01

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

  6. Management of esophageal disorders

    SciTech Connect

    Hill, L.D.; Mercer, C.D.; McCallum, R.W.; Kozarek, R.

    1987-01-01

    This book integrates gastroenterology and thoracic surgery to detail the comprehensive management of esophageal disease. It describes radiologic and functional evaluation of the esophagus, endoscopy, medical and surgical treatments, and results and also covers gastroesophageal reflux disease, tumors motility, esophageal replacement, intubation, esophageal diverticula, caustic esophageal injury. It presents Dr. Hill's surgical procedures in detail.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

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

  10. Esophageal dilation in eosinophilic esophagitis.

    PubMed

    Richter, Joel E

    2015-10-01

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

  11. USP9X expression correlates with tumor progression and poor prognosis in esophageal squamous cell carcinoma

    PubMed Central

    2013-01-01

    Background Ubiquitination is a reversible process of posttranslational protein modification through the action of the family of deubiquitylating enzymes which contain ubiquitin-specific protease 9x (USP9X). Recent evidence indicates that USP9X is involved in the progression of various human cancers. The aim was to detect the expression of USP9X in the progression from normal epithelium to invasive esophageal squamous cell cancer (ESCC) and evaluate the relevance of USP9X expression to the tumor progression and prognosis. Methods In this study, USP9X immunohistochemical analysis was performed on tissues constructed from ESCC combined with either normal epithelium or adjacent precursor tissues of 102 patients. All analyses were performed by SPSS 13.0 software. Results We observed that the level of high USP9X expression increased gradually in the transformation from normal epithelium (4.0%), to low grade intraepithelial neoplasia (10.5%), then to high grade intraepithelial neoplasia (28.6%), and finally to invasive ESCC (40.2%). The expression of USP9X was found to be significantly different between the normal mucosa and ESCC (P < 0.001), and between low grade intraepithelial neoplasia and high grade intraepithelial neoplasia (p = 0.012). However, no difference was observed between the high expression of USP9X in normal mucosa and low grade intraepithelial neoplasia (P = 0.369), nor between high grade intraepithelial neoplasia and ESCC (p = 0.115). Interestingly, the most intensive staining for USP9X was usually observed in the basal and lower spinous layers of the esophageal epithelium with precursor lesions which often resulted in the earliest malignant lesion. USP9X expression status was positively associated with both depth of invasion (p = 0.046) and lymph node metastasis (p = 0.032). Increased USP9X expression was significantly correlated to poorer survival rate in ESCC patients (p = 0.001). When adjusted by multivariate analysis, USP

  12. [Esophageal moniliasis].

    PubMed

    Ramírez Degollado, J; Martínez Aguilar, A; Peniche Bojórquez, J

    1978-01-01

    Esophageal moniliasis is found rarely. It has been described mainly in chronically ill patients, who receive antibiotics and corticoesteroids. Early diagnosis and treatment betters their prognosis. Nine patients, 5 males and 4 females were studies in Hospital General del Centro Medico Nacional in Mexico City. Their agesranged from 26 to 77 years, with a mean of 49 years. All patients were chronically ill and 7 of them were treated in the intensive care unit. Three had disphagia, 3 retrosternal pain, and 2 gastrointestinal hemorrhage. Eight patients had high W.B.C., 3 irregular filling defects on X ray studies, and on endoscopy, all showed a pseudomembranous white yellowish exudate, underneath it the mucosa was inflamed, irregular and bled scantily. In 5 out of 9 patients biopsy and a smear confirmed the diagnosis. Eight patients treated with nystatin were cured. This disorder must be suspected in patients with disphagia and retrosternal pain; esophagoscopy is the prefered procedure to establish this diagnosis.

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1988-07-01

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

  15. Esophageal dilation: simple and effective treatment for adults with eosinophilic esophagitis and esophageal rings and narrowing.

    PubMed

    Bohm, M; Richter, J E; Kelsen, S; Thomas, R

    2010-07-01

    The goal of this article is to present the results of the long-term treatment with esophageal dilation of a consecutive series of adults with eosinophilic esophagitis (EoE). EoE in adults is a disease of middle aged white males, with recurrent food impactions and dysphagia. The exact treatment of EoE is unknown due to the uncertainty of the pathogenesis. Currently, the long-term follow-up of adult EoE patients is limited. Sixteen consecutive adult patients (12 males/4 females between ages 27 and 58 years) with EoE underwent a detailed history and baseline upper gastrointestinal endoscopy (EGD) with multiple esophageal biopsies. Thirteen had esophageal dilation. Fifteen were on proton pump inhibitor (PPI) therapy. After dilation, one patient was treated with a restrictive diet. One patient took prn fluticasone. Most of the patients had allergy testing for food and aeroallergens. Follow-up evaluation with similar testing was on average 22 months (range: 12-40 months). Six patients were not available for follow-up. None of the remaining 10 patients had a food impaction; one required further esophageal dilation. Only two patients had intermittent dysphagia. The average dysphagia score decreased from 2.1 to 0.3 (P < 0.002). The average number of eosinophils at follow-up was not significantly different from baseline (120 eosinophils/HPF proximally and 165 eosinophils/HPF distally (P= 0.75). The gross endoscopy findings were unchanged in all patients except one who normalized. A total of 62% and 75% of patients had positive tests for aeroallergens and food allergens, respectively. Over an average of two years, esophageal dilation provided excellent symptomatic relief among 10 adult EoE patients despite no improvement in the mucosal eosinophilia or gross endoscopic appearance.

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

    PubMed

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

    2011-03-01

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

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

    PubMed

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

    2015-12-14

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

  18. Diagnostic Value of Autoantibodies against Ezrin in Esophageal Squamous Cell Carcinoma

    PubMed Central

    Li, Lan; Liu, Ming; Lin, Jian-Bang; Hong, Xin-Bin; Chen, Wen-Xia; Guo, Hong; Xu, Li-Yan

    2017-01-01

    Esophageal squamous cell carcinoma (ESCC), one of the most common malignancies worldwide, is a highly aggressive and homogeneous entity occurring in esophageal squamous epithelium, and a reliable noninvasive test for early detection is needed. A recent study showed that serum autoantibodies against Ezrin could be detected in patients with pancreatic cancer. Here, we assessed whether autoantibodies against Ezrin could have diagnostic relevance for early ESCC. We analyzed autoantibodies against Ezrin in sera of 98 normal controls and 149 patients with ESCC. Ezrin autoantibodies levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Results showed that higher levels of autoantibodies against Ezrin were observed in serum samples from patients with ESCC than in serum from normal controls (P < 0.0001). Based on a cutoff value of 0.319, the sensitivity and specificity of autoantibodies against Ezrin for diagnosis of ESCC were 27.5% and 95.9%, respectively. Compared with normal controls, the positive rate of autoantibodies against Ezrin was significantly elevated in patients with early-stage ESCC (P < 0.0001). Moreover, there was no significant difference of positivity of autoantibodies against Ezrin in ESCC patients categorized according to age, gender, tumor size, tumor invasion depth, tumor site, histological grade, lymph node status, or tumor stage. Our study indicates that the presence of autoantibodies against Ezrin is significantly associated with ESCC. PMID:28298808

  19. Biomechanics of Esophageal Function in Eosinophilic Esophagitis

    PubMed Central

    Pandolfino, John E

    2012-01-01

    Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by an immune response that leads to symptoms of dysphagia, chest pain, and food impaction. EoE is a clinicopathologic syndrome that requires clinical symptoms and pathologic findings for a diagnosis. The inflammatory process and eosinophilic infiltration of the esophagus in EoE lead to fibrosis and structural changes within the esophagus that cause esophageal dysfunction. The biomechanics of the esophageal function in EoE have been explored using manometry, impedance planimetry, barium esophagograms, and endoscopic ultrasound. These studies have identified several biomechanical changes to the esophagus in EoE including pan-esophageal pressurization on manometry, changes in esophageal compliance with decreased distentisbility by impedance planimetry, decreased esophageal luminal diameter by esophagograms, and dysfunction in the esophageal longitudinal muscles by endoscopic ultrasound. Treatments for the disease involve dietary changes, immunosuppressive drugs, and dilation techniques. However, the data regarding the effect of these therapies on altering mechanical properties of the esophagus is limited. As the pathogenesis of esophageal dysfunction in EoE appears multifactorial, further study of the biomechanics of EoE is critical to better diagnose, monitor and treat the disease. PMID:23105995

  20. Biomechanics of esophageal function in eosinophilic esophagitis.

    PubMed

    Read, Andrew J; Pandolfino, John E

    2012-10-01

    Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease of the esophagus triggered by an immune response that leads to symptoms of dysphagia, chest pain, and food impaction. EoE is a clinicopathologic syndrome that requires clinical symptoms and pathologic findings for a diagnosis. The inflammatory process and eosinophilic infiltration of the esophagus in EoE lead to fibrosis and structural changes within the esophagus that cause esophageal dysfunction. The biomechanics of the esophageal function in EoE have been explored using manometry, impedance planimetry, barium esophagograms, and endoscopic ultrasound. These studies have identified several biomechanical changes to the esophagus in EoE including pan-esophageal pressurization on manometry, changes in esophageal compliance with decreased distentisbility by impedance planimetry, decreased esophageal luminal diameter by esophagograms, and dysfunction in the esophageal longitudinal muscles by endoscopic ultrasound. Treatments for the disease involve dietary changes, immunosuppressive drugs, and dilation techniques. However, the data regarding the effect of these therapies on altering mechanical properties of the esophagus is limited. As the pathogenesis of esophageal dysfunction in EoE appears multifactorial, further study of the biomechanics of EoE is critical to better diagnose, monitor and treat the disease.

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

    PubMed

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

    2014-01-01

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

  2. [Treatment of benign esophageal stenosis: re-evaluation after 20 years].

    PubMed

    Chiocca, J C; Salis; Graciela, B; Stupnik, S; Mazure, P A

    1990-01-01

    In 1972 we described a method for dilatation of esophageal stenosis. The purpose of this paper is to report the results obtained between 1970 and 1989, the patients were studied by X-Rays, "calibration" of the stenosis, endoscopy, biopsy, cytology, gastric analysis and esophageal motility. One hundred and seven patients were treated (mean 60.5 years, M/F 3.9/1). The most frequent etiology was reflux esophagitis (80.3%). Hiatus hernia was present in 84.9%. The stenosis was in the lower third of the esophagus in 92.5%. The BAO was mean: 3.6 mEq/h, and the MAO mean 16.4 mEq/h with a hypersecretion pattern in 33.1% of the cases. Cytology was negative for malignancy in 100%. Biopsy showed esophagitis in 86.9%, Barrett's epithelium in 12.1%, normal tissue in 6.5% and insufficient material in 1.8%. Endoscopy showed 98.1% of grade IV esophagitis. Esophageal motility showed a HPZ of mean 6.5 mmHg. and varying degrees of aperistalsis in 24.3% of the patients. The total number of dilatations was 555 (mean 5.1/pt). The "calibration" of the stenosis previous to the dilatation was mean 8.6 mm, and post dilatation mean 15.6 mm. The result of the procedure was good in 92.5%, regular in 2.8% and bad in 4.6%. The morbidity was 0.9% and the mortality 0.1%. There was relapse of the stenosis in 42% of the cases, the follow-up was mean 3.2 years. Twenty nine patients were submitted to surgery due to failure of the procedure with 68.1% of good results, morbidity of 9% and mortality of 9%. We conclude that this dilatation procedure offers excellent results with a very low morbi-mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  5. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

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

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

    SciTech Connect

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

    1981-05-01

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

  7. RANK overexpression as a novel esophageal cancer marker: validated immunohistochemical analysis of two different ethnicities

    PubMed Central

    Cui, Xiaobin; Peng, Hao; Jin, Jing; Li, Tingting; Zhang, Shumao; Jin, Tingting; Li, Su; Liu, Chunxia; Liang, Weihua; Li, Feng; Chen, Yunzhao

    2015-01-01

    This study aimed to evaluate the receptor activator of nuclear factor-κB (RANK) expression statuses of esophageal squamous cell carcinoma (ESCC) patients, high-grade intraepithelial neoplasia (HGIN), low-grade intraepithelial neoplasia (LGIN), and normal esophageal tissues (NETs) in Chinese Han and Kazakh ethnic, as well as the correlation of RANK expression with clinicopathological characteristics. RANK immunohistochemical analysis was conducted to investigate the expression of RANK in 113 ESCC, 36 HGIN, 63 LGIN, and 98 NETs from Han ethnic patients and in 196 ESCC and 76 NETs from Kazakh ethnic patients. The associations of RANK expression with ethnic and clinicopathological characteristics were examined using χ2-test. Upregulated RANK expression was detected in both Han and Kazakh ethnic ESCC tissues, compared with NETs (P = 1.11×10-5, 0.001, respectively). RANK expression was significantly increased during malignant transformation from normal epithelium into LGIN (P = 2.84×10-7) and HGIN (P = 7.83×10-6) tissues in Han ethnic patients. The increased expression of RANK also correlated with lymph node metastasis in Kazakh ethnic ESCC patients (P = 0.019). By contrast, no significant correlation existed between RANK expression and clinicopathological characteristics of Han ethnic ESCC patients. Furthermore, Kaplan-Meier survival analysis showed that ESCC patients with higher expression of RANK protein had significantly worse prognosis than ESCC patients with low or no expression (P = 0.001). In conclusion, this study is the first to identify RANK overexpression as a novel esophageal cancer marker in both Kazakh and Han ethnic ESCC patients. The results support the association of RANK with ESCC across ethnicities. In summary, RANK could be a therapeutic target in ESCC patients. PMID:25973136

  8. Distal esophageal spasm: an update.

    PubMed

    Achem, Sami R; Gerson, Lauren B

    2013-09-01

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

  9. Genetics of Eosinophilic Esophagitis

    DTIC Science & Technology

    2012-03-01

    in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR (C) for esophageal...microscopy and morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants...most highly associated variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor

  10. Diet and esophageal disease

    PubMed Central

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

    2014-01-01

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

  11. Effect of physical exercise on esophageal motility in patients with esophageal disease.

    PubMed

    Ravi, N; Stuart, R C; Byrne, P J; Reynolds, J V

    2005-01-01

    The most common type of esophageal dysfunction associated with chest pain is gastroesophageal reflux, which may be induced by exercise. The effect of exercise on esophageal function has mainly been investigated in normal subjects or trained athletes. Few studies have investigated exercise and esophageal motility disorders. One hundred and thirty-five patients underwent ambulatory esophageal manometry and pH monitoring, before, during and immediately after moderate exercise. Patients were divided into four groups: Normal, nutcracker, diffuse spasm and gastroesophageal reflux disease (GERD). Ambulatory manometry and pH were monitored while exercising on a treadmill during which standardized boluses of water were administered. Nutcracker and diffuse spasm patients demonstrated a significant fall in esophageal wave amplitude during exercise compared to controls, which returned rapidly to pre exercise values after resting. There was no evidence of acid reflux in the non-reflux groups during exercise. Reflux was noted in 13 patients with GERD during exercise, none of whom had evidence of reflux at the onset of exercise. When these patients were classified by reflux type, the majority, 11 patients, were found to come from the combined or supine reflux group. Esophageal amplitude in nutcracker esophagus does not increase during moderate exercise. Moderate exercise provokes reflux in GERD patients with combined or supine reflux.

  12. The integrity of the esophageal mucosa. Balance between offensive and defensive mechanisms.

    PubMed

    Orlando, Roy C

    2010-12-01

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

  13. Radionuclide transit in esophageal varices

    SciTech Connect

    Yeh, S.H.; Wang, S.J.; Wu, L.C.; Liu, R.S.; Tsai, Y.T.; Chiang, T.T.

    1985-05-01

    This study assessed esophageal motility in patients with esophageal varices by radionuclide transit studies. Data were acquired in list mode after an oral dose of 0.5 mCi Tc-99m sulfur colloid in 10 ml of water in the supine position above a low-energy all-purpose collimator of a gamma camera. The condensed image (CI) superimposed with a centroid curve was also produced in each case. Twenty-five normal subjects (N) and 32 patients (pts) with esophageal varices by endoscopy (large varices in Grades IV and V in 8 and small varices in Grade III or less in 24) were studied. TMTT, RTT, RF, and RI were all significantly increased in pts as compared to N. Especially, the transit time for the middle third (6.7 +- 2.6 sec vs 3.5 +- 0.9 sec in N, rho < 0.005) had the optimal sensitivy and specificity of 88% each at the cutoff value of 4.2 sec as determined by ROC analysis. In summary, radionuclide transit disorders occur in the majority of pts with esopageal varices. The middle RTT and CI are both optimal in sensitivity and specificity for detecting the abnormalities.

  14. Eosinophilic Esophagitis: an Emerging Clinicopathologic Disease of Children and Adults

    PubMed Central

    Straumann, Alex

    2006-01-01

    Eosinophililc esophagitis is a clinicopathologic disease characterized clinically by dysphagia and food impaction in adults and nonspecific symptoms of gastroesophageal reflux disease in children, and histologically by large numbers of eosinophils in the proximal and distal esophageal epithelium. Importantly, these symptoms and histologic abnormalities appear to be unresponsive to proton pump inhibition. Recent clinical and basic studies suggest an allergic etiology but the precise allergen remains unknown and is likely unique for each patient. Endoscopic features suggest ongoing inflammation and range from linear furrowing with whitish exudation to long-segment stricture formation, to a fragile, crepe paper–like mucosa that is easily split open. Treatments include nutritional restrictions, medical management with topical steroids, and, in stenotic circumstances, esophageal dilation. The long-term outcome is still not certain.

  15. Ductal barriers in mammary epithelium

    PubMed Central

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

    2013-01-01

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

  16. 5-ALA/PpIX fluorescence detection of esophageal and stomach neoplasia: effects of autofluorescence background from normal and inflammatory areas

    NASA Astrophysics Data System (ADS)

    Borisova, Ekaterina; Vladimirov, Borislav; Avramov, Lachezar

    2008-12-01

    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.

  17. Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma.

    PubMed

    Kumagai, Youichi; Sobajima, Jun; Higashi, Morihiro; Ishiguro, Toru; Fukuchi, Minoru; Ishibashi, Keiichiro; Mochiki, Erito; Yakabi, Koji; Kawano, Tatsuyuki; Tamaru, Jun-ichi; Ishida, Hideyuki

    2015-04-01

    Using immunohistochemical staining, the present study was conducted to examine whether cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) affect angiogenesis in early-stage esophageal squamous cell carcinoma (ESCC). We also analyzed the correlation between these two factors. Cyclooxygenase 2, iNOS, and angiogenesis in early-stage ESCC are unclear. Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia (LGIN), and 45 samples of superficial esophageal cancer, we observed the expression of COX-2 and iNOS. We then investigated the COX-2 and iNOS immunoreactivity scores and the correlation between COX-2 or iNOS scores and microvessel density (MVD) using CD34 or CD105. The intensity of COX-2 or iNOS expression differed significantly according to histological type (P < 0.001). The scores of COX-2 and iNOS were lowest for normal squamous epithelium, followed in ascending order by LGIN, carcinoma in situ and tumor invading the lamina propria mucosae (M1-M2 cancer); and tumor invading the muscularis mucosa (M3) or deeper cancer. The differences were significant (P < 0.001). Cancers classified M1-M2 (P < 0.01 and P < 0.05, respectively); M3; or deeper cancer (P < 0.01) had significantly higher COX-2 and iNOS scores than normal squamous epithelium. There was a significant correlation between COX-2 and iNOS scores (P < 0.001, rs = 0.51). Correlations between COX-2 score and CD34-positive MVD or CD105-positive MVD were significant (rs = 0.53, P < 0.001; rs = 0.62, P < 0.001, respectively). Inducible nitric oxide synthase score was also significantly correlated with CD34 MVD and CD105 MVD (rs = 0.45, P < 0.001; rs = 0.60, P < 0.001, respectively). Chemoprevention of COX-2 or iNOS activity may blunt the development of ESCC from precancerous lesions.

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

    PubMed Central

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

    2013-01-01

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

  19. Lymphocytic esophagitis: Still an enigma a decade later

    PubMed Central

    Rouphael, Carol; Gordon, Ilyssa O; Thota, Prashanthi N

    2017-01-01

    Lymphocytic esophagitis (LE) is a clinicopathologic entity first described by Rubio et al in 2006. It is defined as peripapillary intraepithelial lymphocytosis with spongiosis and few or no granulocytes on esophageal biopsy. This definition is not widely accepted and the number of lymphocytes needed to make the diagnosis varied in different studies. Multiple studies have described potential clinical associations and risk factors for LE, such as old age, female gender and smoking history. This entity was reported in inflammatory bowel disease in the pediatric population but not in adults. Other associations include gastroesophageal reflux disease and primary esophageal motility disorders. The most common symptom is dysphagia, with a normal appearing esophagus on endoscopy, though esophageal rings, webs, nodularities, furrows and strictures have been described. Multiple treatment modalities have been used such as proton pump inhibitors and topical steroids. Esophageal dilation seems to be therapeutic when dysphagia is present along with esophageal narrowing secondary to webs, rings or strictures. The natural history of the disease remains unclear and needs to be better delineated. Overall, lymphocytic esophagitis seems to have a chronic and benign course, except for two cases of esophageal perforation in the literature, thought to be secondary to this entity. PMID:28246468

  20. Lymphocytic esophagitis: Still an enigma a decade later.

    PubMed

    Rouphael, Carol; Gordon, Ilyssa O; Thota, Prashanthi N

    2017-02-14

    Lymphocytic esophagitis (LE) is a clinicopathologic entity first described by Rubio et al in 2006. It is defined as peripapillary intraepithelial lymphocytosis with spongiosis and few or no granulocytes on esophageal biopsy. This definition is not widely accepted and the number of lymphocytes needed to make the diagnosis varied in different studies. Multiple studies have described potential clinical associations and risk factors for LE, such as old age, female gender and smoking history. This entity was reported in inflammatory bowel disease in the pediatric population but not in adults. Other associations include gastroesophageal reflux disease and primary esophageal motility disorders. The most common symptom is dysphagia, with a normal appearing esophagus on endoscopy, though esophageal rings, webs, nodularities, furrows and strictures have been described. Multiple treatment modalities have been used such as proton pump inhibitors and topical steroids. Esophageal dilation seems to be therapeutic when dysphagia is present along with esophageal narrowing secondary to webs, rings or strictures. The natural history of the disease remains unclear and needs to be better delineated. Overall, lymphocytic esophagitis seems to have a chronic and benign course, except for two cases of esophageal perforation in the literature, thought to be secondary to this entity.

  1. Frequency of eosinophilic esophagitis in patients with esophageal symptoms: a single-center Turkish experience.

    PubMed

    Altun, R; Akbas, E; Yıldırım, A E; Öcal, S; Korkmaz, M; Selcuk, H

    2013-01-01

    Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease characterized with symptoms related to esophageal dysfunction and eosinophil-predominant inflammation. There has been a dramatic increase in the diagnosis of this disease in recent years. The primary objective of this study was to determine the frequency of EoE in adult patients who were evaluated by gastroenterologists in our clinic with esophageal symptoms. Between November 2010 and May 2011, 311 adult patients who were evaluated in our clinic with esophageal symptoms were enrolled prospectively. All patients underwent endoscopy and had biopsies taken. Gastroesophageal reflux disease was excluded by either proton pump inhibitory treatment or 24-hour ambulatory pH monitorization. The diagnosis was confirmed by one independent pathologist. Frequency of EoE in patients with esophageal symptoms was 2.6% (n = 8; four men and four women). Mean age at diagnosis was 40.2 ± 8 years. Heartburn was the predominant symptom in patients (75% of the patients), and 87.5% (n = 7) of patients had more than one symptom at diagnosis. Nearly 38% of the patients (n = 3) had a history of allergic disease. Endoscopic findings were as follows: transient/fixed esophageal rings (25%), white exudates (25%), and normal appearance (50%). Median number of circulating eosinophils was 208 (93-659)/mm(3) . Median number of intraepithelial eosinophils in proximal-middle 1/3 part and distal 1/3 part of esophagus were 0 (0-50)/hpf and 37 (16-50)/hpf, respectively. In conclusion, EoE is not rare in Turkey, and it should be considered in the differential diagnosis of patients with esophageal symptoms.

  2. Axial force measurement for esophageal function testing

    PubMed Central

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

    2009-01-01

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

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

    ClinicalTrials.gov

    2017-04-13

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

    Objective The aim of the present study was to clarify differences between micro-vascular and iodine-staining patterns in the vicinity of the tumor fronts of superficial esophageal squamous cell carcinomas (ESCCs). Methods Ten consecutive patients with ESCCs who were treated by endoscopic submucosal dissection (ESD) were enrolled. At the edge of the iodine-unstained area, we observed 183 sites in total using image-enhanced magnifying endoscopy. We classified the micro-vascular and iodine-staining patterns into three types: Type A, in which the line of vascular change matched the border of the iodine-unstained area; Type B, in which the border of the iodine-unstained area extended beyond the line of vascular change; Type C, in which the line of vascular change extended beyond the border of the iodine-unstained area. Then, by examining histopathological sections, we compared the diameter of intra-papillary capillary loops (IPCLs) in cancerous areas and normal squamous epithelium. Results We investigated 160 sites that the adequate quality of pictures were obtained. There was no case in which the line of vascular change completely matched the whole circumference of the border of an iodine-unstained area. Among the 160 sites, type A was recognized at 76 sites (47.5%), type B at 79 sites (49.4%), and type C at 5 sites (3.1%). Histological examination showed that the mean diameter of the IPCLs in normal squamous epithelium was 16.2±3.7μm, whereas that of IPCLs in cancerous lesions was 21.0±4.4μm. Conclusions The development of iodine-unstained areas tends to precede any changes in the vascularity of the esophageal surface epithelium. PMID:26301414

  6. [Primary esophageal lymphoma].

    PubMed

    Ximenes, Manoel; Piauilino, Marcos Amorim; Oliveira, Humberto Alves; Vaz Neto, Jorge Pinto

    2012-01-01

    We describe the case of a 54 year old woman seen with an esophageal mass diagnosed as a primary esophageal lymphoma. The main symptom was dysphagia of seven months duration. The treatment consisted in resection of the tumor, and reconstruction of the defect with a reversed pleural flap, followed by a chemotherapy regimen that consisted of five drugs, cyclophosphamid, prednisone, doxorubicin, rituximab and vincristine (R-CHOP). The patient developed an esophageal pleural fistula treated with pleural drainage and irrigation that closed in 45 days. Two and one half years later she is doing well and disease free.

  7. Diffuse esophageal spasm in children referred for manometry.

    PubMed

    Rosen, John M; Lavenbarg, Teri; Cocjin, Jose; Hyman, Paul E

    2013-04-01

    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.

  8. High Mobility Group A proteins in esophageal carcinomas.

    PubMed

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

    2016-09-16

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

  9. Radionuclide esophageal transit: an evaluation of therapy in achalasia

    SciTech Connect

    McKinney, M.K.; Brady, C.E.; Weiland, F.L.

    1983-09-01

    We measured quantitative esophageal transit, expressed as percentage of esophageal retention, before and after pneumatic dilatation in two patients with achalasia. In the sitting position they ingested a 500 ml liquid meal containing 500 muCi technetium Tc 99m sulfur colloid. Radioactivity counts of the entire esophagus were plotted at five-minute intervals for 30 minutes. In five normal control subjects the esophagus essentially cleared in less than one minute. Both patients with achalasia had definite retention 30 minutes before dilatation and had quantitative improvement after dilatation. Radionuclide scintigraphic esophageal transit probably correlates better than other parameters with the physiologic degree of obstruction in achalasia.

  10. Lymphocytic esophagitis: Report of three cases and review of the literature

    PubMed Central

    Jideh, Bilel; Keegan, Andrew; Weltman, Martin

    2016-01-01

    Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema (“spongiosis”). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn’s disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. LyE has been reported to run a benign course; however there has been a case of esophageal perforation associated with LyE. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature. PMID:28035315

  11. Esophageal stricture - benign

    MedlinePlus

    ... esophagus. These may include household cleaners, lye, disc batteries, or battery acid. Treatment of esophageal varices Symptoms Symptoms may ... Prognosis) The stricture may come back in the future. This would require a repeat dilation. Possible Complications ...

  12. Stages of Esophageal Cancer

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  13. Snapshot of Esophageal Cancer

    MedlinePlus

    ... consortium of three translational research centers studying the origins and pathogenesis of esophageal cancer, with the ultimate goal of improving patient outcomes and decreasing the burden of the disease. One center is studying the genetic basis of ...

  14. Esophageal motility in nonacid reflux compared with acid reflux.

    PubMed

    Wang, Victor S; Feldman, Natan; Maurer, Rie; Burakoff, Robert

    2009-09-01

    Esophageal motility has been well studied in gastroesophageal reflux disease (GERD) and acid reflux, but not in nonacid reflux. Consecutive patients who had both 24-h multichannel intraluminal impedance-pH (MII-pH) and esophageal motility tests for suspected GERD were studied. Patients were grouped into nonacid refluxers, acid refluxers, and nonrefluxers based on positive symptom correlation and objective findings of acid reflux. Of 96 patients enrolled, 21 patients (22%) were nonacid refluxers, 44 patients (46%) were acid refluxers, and 31 patients (32%) had no objective evidence of reflux. Normal motility was recorded in 86% of nonacid refluxers, 71% of acid refluxers, and 60% of nonrefluxers. Ineffective esophageal motility was seen in 24% of acid refluxers, and 5% of nonacid refluxers (P = 0.11). Symptomatic nonacid reflux events comprised 22% of patients studied for GERD symptoms by MII-pH. Esophageal motility in nonacid reflux is normal 86% of the time.

  15. Genetics of Eosinophilic Esophagitis

    DTIC Science & Technology

    2011-03-01

    staining for major basic protein in esophageal tissue (arrowheads) in WT than IL21R-/- mice (A) is quantified morphometrically in (B). Quantitative PCR... morphometric analysis was used to measure IL21 receptor expression in patient esophageal biopsies. RESULTS: A number of genetic variants on chromosome 4q26-27...variants in the locus. Immunofluorescent microscopy and morphometric analysis demonstrate a marked increase in IL21 receptor- expressing cells within

  16. Oral and esophageal disorders.

    PubMed

    Noyer, C M; Simon, D

    1997-06-01

    This article focused on the approach to oral and esophageal disorders in patients with AIDS. Most of these disorders respond to various therapeutic regimens. Some of the oral complications can be prevented with dental prophylaxis, whereas recurrent esophageal disease in some patients may require long-term suppressive therapy. As patients with AIDS live longer with lower CD4 counts, gastroenterologists need to become familiar with the approach to and management of the more common lesions of the mouth and esophagus.

  17. COX2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

    PubMed Central

    Dawsey, Sonja P.; Roth, Mark J.; Adams, Lisa; Hu, Nan; Wang, Quan-Hong; Taylor, Philip R.; Woodson, Karen

    2008-01-01

    Background Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor-stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma. Methods Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing. Results Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher’s Exact p=0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples. Conclusions In these esopohageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations. Condensed abstract COX2 (PTGS2) gene

  18. [Congenital Esophageal Atresia].

    PubMed

    Suzuki, Makoto; Kuwano, Hiroyuki

    2015-07-01

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

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

    PubMed

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

    2015-01-01

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

  20. Ineffective esophageal motility (IEM): the primary finding in patients with nonspecific esophageal motility disorder.

    PubMed

    Leite, L P; Johnston, B T; Barrett, J; Castell, J A; Castell, D O

    1997-09-01

    Nonspecific esophageal motility disorder (NEMD) is a vague category used to include patients with poorly defined esophageal contraction abnormalities. The criteria include "ineffective" contraction waves, ie, peristaltic waves that are either of low amplitude or are not transmitted. The aim of this study was to identify the prevalence of ineffective esophageal motility (IEM) found during manometry testing and to evaluate esophageal acid exposure and esophageal acid clearance (EAC) in patients with IEM compared to those with other motility findings. We analyzed esophageal manometric tracings from 600 consecutive patients undergoing manometry in our laboratory following a specific protocol from April 1992 through October 1994 to identify the frequency of ineffective contractions and the percentages of other motility abnormalities present in patients meeting criteria for NEMD. Comparison of acid exposure and EAC was made with 150 patients who also had both esophageal manometry and pH-metry over the same time period. Sixty-one of 600 patients (10%) met the diagnostic criteria for NEMD. Sixty of 61 (98%) of these patients had IEM, defined by at least 30% ineffective contractions out of 10 wet swallows. Thirty-five of these patients also underwent ambulatory esophageal pH monitoring. Patients with IEM demonstrated significant increases in both recumbent median percentage of time of pH <4 (4.5%) and median distal EAC (4.2 min/episode) compared to those with normal motility (0.2%, 1 min/episode), diffuse esophageal spasm (0%, 0.6 min/episode), hypertensive LES (0%, 1.8 min/episode), and nutcracker esophagus (0.4% 1.6 min/episode). Recumbent acid exposure in IEM did not differ significantly from that in patients with systemic scleroderma (SSc) for either variable (5.4%, 4.2 min/episode). We propose that IEM is a more appropriate term and should replace NEMD, giving it a more specific manometric identity. IEM patients demonstrate a distinctive recumbent reflux pattern

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

    SciTech Connect

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

    1984-10-01

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

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

    PubMed

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

    2012-11-01

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

  3. New Variant of Esophageal Atresia

    PubMed Central

    Harne, Swapnil; Pathak, Manish; Rattan, Kamal Nayan

    2017-01-01

    Esophageal atresia with tracheoesophageal fistula (EA/TEF) associated with distal congenital esophageal stenosis (CES) is a well-known entity. We encountered three patients of EA/TEF associated with long and unusual CES. PMID:28083495

  4. A submucosal tumor-like recurrence of early esophageal cancer after endoscopic submucosal dissection.

    PubMed

    Choi, Jeong Cheon; Kim, Gwang Ha; Park, Do Youn; Seoung, Hyeog Gyu; Lee, Yong Jae; Kim, Ji Hye; Kim, Tae Kyun; I, Hoseok

    2013-03-01

    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.

  5. The Esophageal Propulsive Force: Esophageal Response to Acute Obstruction*

    PubMed Central

    Winship, Daniel H.; Zboralske, F. Frank

    1967-01-01

    The response of the normal human esophagus to an obstructing intraluminal bolus was investigated and compared to the response evoked by transient intraluminal distention. A balloon, immobilized within the esophagus by external attachment to a force transducer, was inflated with from 3 to 25 ml of air for from 3 to 210 sec. Pressure phenomena occurring in the esophagus were simultaneously recorded from the body of the esophagus above and below the balloon. Transient distention (5 sec or less) with small volumes (5 ml or less) often evoked a secondary peristaltic wave in the esophagus distal to the balloon, but infrequently resulted in the registration of any force exerted upon the balloon to drive it downward. Conversely, distentions of longer duration and with greater volume elicited an esophageal propulsive force exerted upon the balloon oriented to propel it aborally, and much less often evoked a propagated wave of secondary peristalsis. The propulsive force, obviously resulting from esophageal muscular contraction, occurred promptly, and once initiated, was sustained until deflation of the balloon. It varied widely in magnitude, from 4 to 200 g, and was associated with no motor phenomena recorded from the body of the esophagus proximal or distal to the balloon which could account for its presence, onset, magnitude, or duration. The force was inhibited by deglutition, but arrival of the primary peristaltic wave at the bolus resulted in augmentation of the force. When the obstructing balloon was freed from its attachment, the persistent, stationary force was converted to a propagated one that propelled the balloon before it. It the balloon was arrested before entering the stomach, the moving contraction was also arrested and the persistent propulsive force acting upon the balloon was maintained. The velocity of the moving contraction wave was determined in great part by the resistance offered by the bolus. Unrestrained, the balloon was propelled aborally at 4-8 cm

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

    SciTech Connect

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

    1985-04-01

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

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

    PubMed Central

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

    2016-01-01

    Background Tenascin-C, an adhesion modulatory extracellular matrix molecule, is highly expressed in numerous human malignancies; thus, it may contribute to carcinogenesis and tumor progression. We explored the clinicopathological significance of Tenascin-C as a prognostic determinant of esophageal squamous cell carcinoma (ESCC). Methods In ESCC patient tissues and cell lines, the presence of isoforms were examined using western blotting. We then investigated Tenascin-C immunohistochemical expression in 136 ESCC tissue samples. The clinical relevance of Tenascin-C expression and the correlation between Tenascin-C expression and expression of other factors related to cancer-associated fibroblasts (CAFs) were also determined. Results Both 250 and 350 kDa sized isoforms of Tenascin-C were expressed only in esophageal cancer tissue not in normal tissue. Furthermore, both isoforms were also identified in all of four CAFs derived from esophageal cancer tissues. Tenascin-C expression was remarkably higher in ESCC than in adjacent non-tumor esophageal epithelium (p < 0.001). Tenascin-C expression in ESCC stromal fibroblasts was associated with patient’s age, tumor (pT) stage, lymph node metastasis, clinical stage, and cancer recurrence. Tenascin-C expression in cancer cells was correlated with an increase in tumor-associated macrophage (TAM) population, cancer recurrence, and hypoxia inducible factor1α (HIF1α) expression. Moreover, Tenascin-C overexpression in cancer cells and stromal fibroblasts was an independent poor prognostic factor for overall survival (OS) and disease-free survival (DFS). In the Cox proportional hazard regression model, Tenascin-C overexpression in cancer cells and stromal fibroblasts was a significant independent hazard factor for OS and DFS in ESCC patients in both univariate and multivariate analyses. Furthermore, Tenascin-C expression in stromal fibroblasts of the ESCC patients was positively correlated with platelet-derived growth factor

  8. Reduced expression of cytokeratin 4 and 13 is a valuable marker for histologic grading of esophageal squamous intraepithelial neoplasia.

    PubMed

    Takashima, Masaki; Kawachi, Hiroshi; Yamaguchi, Tsukasa; Nakajima, Yutaka; Kitagaki, Keisuke; Sekine, Masaki; Iida, Tadatsune; Takemura, Kosuke; Kawano, Tatsuyuki; Eishi, Yoshinobu

    2012-03-13

    Histologic evaluation of low-grade or high-grade intraepithelial neoplasia (LG-IN or HG-IN) of the esophagus is important for estimating the risk of progression to invasive carcinoma. Discrimination between LG-IN and HG-IN, or neoplasia and non-neoplastic lesion (NNL), however, is occasionally difficult. This study was designed to evaluate whether cytokeratin expression can be used for discrimination of these lesions. Esophageal Iodine-unstained lesions (n=154), less than 10 mm, were classified into HG-IN, LG-IN, and NNL. These lesions together with 154 foci of normal esophageal epithelium (NEE) were examined by immunohistochemistry for cytokeratins (CK4 and CK13), p53 overexpression, and the MIB-1 labeling index. The ratios of CK4- and CK13-positive staining were scored from 1 to 3. The CK4- and CK13-positive staining ratios were decreased in NNL (73% and 78%), LG-IN (55% and 69%), and HG-IN (33% and 48%), compared to NEE (91% and 95%). The differences between LG-IN and HG-IN, neoplasia and NNL, and among these three lesions and NEE were statistically significant (p < 0.005). The cytokeratin scores correlated with the MIB-1 labeling index (both: p < 0.0001), but not with p53 overexpression. CK4 and CK13 immunohistochemistry could be an objective method for evaluating the risk for progression to invasive carcinoma.

  9. Multilayered epithelium at the gastroesophageal junction is a marker of gastroesophageal reflux disease: data from a prospective Central European multicenter study (histoGERD trial).

    PubMed

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

    2014-04-01

    Multilayered epithelium is defined as hybrid epithelium with characteristics of both squamous and columnar epithelia. Our aim was to evaluate the clinicopathological significance of the lesion by relating its presence to various histological and clinical and/or endoscopic features indicating gastroesophageal reflux disease (GERD). A total of 1,071 individuals participated in a prospective cross-sectional study (576 females and 495 males; median age 53 years). Biopsy material was systematically sampled from the gastroesophageal junction. The histological diagnosis of esophagitis was made according to the Esohisto consensus guidelines. The endoscopic diagnosis of esophagitis was made according to the modified Los Angeles classification and the diagnosis of Barrett's esophagus according to Prague's C & M criteria, respectively. Multilayered epithelium was identified in 103 (9.6 %) individuals, frequently within or adjacent to the ducts of esophageal glands. Its presence was associated with increasing age (p < 0.001), high BMI (p = 0.026), hiatal hernia (p < 0.001), and the endoscopic diagnoses of esophagitis (p = 0.002) and Barrett's esophagus (p < 0.001). Upon histology, multilayered epithelium was associated with features of the squamous epithelium indicating GERD, particularly intercellular space dilation (p = 0.005), and presence of cardiac mucosa (<0.001). For intestinal metaplasia, a trend was noted (p = 0.094). In conclusion, multilayered epithelium was observed in about every tenth individual undergoing upper gastrointestinal endoscopy. The association with histological and clinical features indicating GERD advocates the lesion as a promising new marker for reflux esophagitis. The association with cardiac mucosa and Barrett's esophagus suggests multilayered epithelium to be an intermediate step in the development of columnar metaplasia and, ultimately, Barrett's esophagus.

  10. Chemoradiotherapy for Esophageal Cancer

    PubMed Central

    Patel, Ashish; Suntharalingam, Mohan

    2009-01-01

    Radiotherapy and surgery have both played prominent roles in the treatment of esophageal cancer since the beginning of the 20th century. Although the use of radiotherapy alone to treat esophageal cancer has a long history, it has not demonstrated improved outcomes compared with surgery alone. The disappointing rates of survival and local control associated with single-modality therapy and the need for effective nonsurgical management led to the development of definitive chemoradiotherapy paradigms for esophageal cancer. Adding cytotoxic chemotherapy to radiotherapy for additive or synergistic effect was described as early as 1968, and over time, treatment has shifted from single-modality therapy toward combined-modality therapy using chemotherapy and radiotherapy. This approach eventually demonstrated superior outcomes in patients with esophageal cancer when compared to radiotherapy alone. Maximum benefit of this therapy depends on the appropriate addition of surgery and the optimization of radiosensitizing chemotherapy. A burgeoning area of research has focused on improving definitive chemoradiotherapy strategies through the incorporation of newer chemotherapeutic agents and targeted biologic agents. An overview of the history of chemoradiotherapy in the treatment of esophageal cancer is presented, as well as a discussion of ongoing studies and future areas of promising research. PMID:19461907

  11. Intramural esophageal tumors

    PubMed Central

    Kozak, Katarzyna; Rębowski, Marek; Kozak, Józef

    2016-01-01

    Introduction Intramural esophageal tumors (IET) are located between unchanged mucous membrane and muscularis mucosae. They can be both benign and malignant. Aim To evaluate diagnostic and therapeutic difficulties of IET. Material and methods During the years 2010–2015, 11 patients with IET were treated in our clinic. Diagnostics included gastroscopy, computed tomography of the chest, endoscopic ultrasound (EUS) guided fine needle biopsy, and positron emission tomography (PET) of the esophagus in cases with no histopathological confirmation. Results Based on the conducted analysis we diagnosed 1 case of gastrointestinal stromal tumor (GIST), 1 case of adenocarcinoma, and 2 cases of esophageal cysts. In another 7 cases radiological images resembled leiomyoma but with no histopathological confirmation. Esophagectomy was performed in 2 cases of malignant tumors and 1 case of a large benign tumor. In other cases surgical enucleation of tumors was performed. Postoperatively we diagnosed 6 cases of leiomyoma, 1 case of schwannoma, 2 esophageal cysts, 1 case of GIST and 1 of esophageal cancer. Conclusions Intramural esophageal tumors is a very diverse group of tumors, both malignant and benign. In every case of IET we should seek histopathological conformation. Treatment of IET depends on localization, size and histopathological type of lesion. PMID:28096828

  12. Esophageal tissue engineering.

    PubMed

    Luc, Guillaume; Durand, Marlène; Collet, Denis; Guillemot, Fabien; Bordenave, Laurence

    2014-03-01

    Esophageal tissue engineering is still in an early state, and ideal methods have not been developed. Since the beginning of the 20th century, advances have been made in the materials that can be used to produce an esophageal substitute. Three approaches to scaffold-based tissue engineering have yielded good results. The first development concerned non-absorbable constructs based on silicone and collagen. The need to remove the silicone tube is the main disadvantage of this material. Polymeric absorbable scaffolds have been used since the 1990s. The main polymeric material used is poly (glycolic) acid combined with collagen. The problem of stenosis remains prevalent in most studies using an absorbable construct. Finally, decellularized scaffolds have been used since 2000. The promises of this new approach are unfulfilled. Indeed, stenosis occurs when the esophageal defect is circumferential regardless of the scaffold materials. Cell supplementation can decrease the rate of stenosis, but the type(s) of cells and their roles have not been defined. Finally, esophageal tissue engineering cannot provide a functional esophageal substitute, and further development is necessary prior to conducting human clinical studies.

  13. Low mean impedance in 24-hour tracings and esophagitis in children: a strong connection.

    PubMed

    Salvatore, S; Salvatoni, A; Ummarino, D; Ghanma, A; Van der Pol, R; Rongen, A; Fuoti, M; Meneghin, F; Benninga, M Alexander; Vandenplas, Y

    2016-01-01

    Esophageal multiple intraluminal impedance baseline is an additional impedance parameter that was recently related to esophageal integrity. The aim of this study was to assess the relationship between mean esophageal impedance value and endoscopic findings in a large group of children. Children with symptoms of gastroesophageal reflux submitted to both endoscopy and impedance were included. Esophagitis was graded according to the Los Angeles classification. Mean impedance value was automatically calculated over 24-hour tracings. Data were adjusted for age through z-score transformation using percentiles normalized by the LMS (Lambda for the skew, Mu for the median, and Sigma for the generalized coefficient of variation) method. Nonparametric Mann-Whitney and Kruskal-Wallis tests, multiple, and stepwise regression were used. P-value <0.05 was considered as statistically significant. A total of 298 impedance tracings were analyzed. Endoscopic and histological esophagitis were detected in 30 and 29% patients, respectively. Median baseline z-score was significantly decreased both in proximal (P = 0.02) and distal (P = 0.01) esophagus in patients with endoscopic (but not histological) esophagitis. Patients with more severe esophagitis showed the lowest z-score. Bolus exposure index and the number of reflux episodes were the variables that were significantly associated with the baseline z-score. Impedance z-score is significantly decreased in infants and children with endoscopic esophagitis. Severity of esophagitis, bolus exposure index, and number of reflux episodes are factors influencing mean esophageal impedance.

  14. Changes in esophageal motility after porfimer sodium photodynamic therapy for Barrett's dysplasia and mucosal carcinoma.

    PubMed

    Shah, A K; Wolfsen, H C; Hemminger, L L; Shah, A A; DeVault, K R

    2006-01-01

    Esophageal dysmotility is common in patients with Barrett's esophagus. Previously we have reported deterioration of esophageal motility after photodynamic therapy (PDT) in a heterogeneous group of patients with esophageal carcinoma. This prospective study in consecutive patients describes changes in motility noted after endoscopic ablation. Forty-seven patients referred to our institution for endoscopic ablation for Barrett's high grade dysplasia or mucosal carcinoma between August 2001 and May 2003 were prospectively evaluated with esophageal manometry before and after porfimer sodium PDT. Six patients did not complete the study. Manometry results were classified as normal, diffuse esophageal spasm, ineffective esophageal motility, or aperistalsis. Abnormal esophageal motility was found in 14 of 47 (30%) patients at study entry ([diffuse esophageal spasm] DES-3, [ineffective esophageal motility] IEM-7, Aperistalsis-4). After PDT, 11 of 41 patients with paired studies experienced a change in manometric diagnosis. Three patients had an improvement in motility, seven a worsening and one changed diagnosis, but did not particularly worsen or improve. No patient developed new aperistalsis. Therefore, abnormal motility was present in 19 of 41 (46%) patients after PDT (DES-2, IEM-14, Aperistalsis-3). There was a statistically significant (P = 0.016) relationship with longer segment Barrett's esophagus and deterioration of function. Baseline abnormalities in motility can occur in patients with Barrett's high-grade dysplasia or mucosal carcinoma. Changes in esophageal function also may occur following photodynamic therapy, but usually are not clinically significant. Worsening in function was more likely to occur in patients with longer segment Barrett's esophagus.

  15. Minimally invasive surgery for esophageal achalasia.

    PubMed

    Chen, Huan-Wen; Du, Ming

    2016-07-01

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

  16. Assessing esophageal dysphagia.

    PubMed

    Kruger, Danielle

    2014-05-01

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

  17. Simulation studies of the role of esophageal mucosa in bolus transport.

    PubMed

    Kou, Wenjun; Pandolfino, John E; Kahrilas, Peter J; Patankar, Neelesh A

    2017-01-03

    Based on a fully coupled computational model for esophageal transport, we analyzed the role of the mucosa (including the submucosa) in esophageal bolus transport and how bolus transport is affected by mucosal stiffness. Two groups of studies were conducted using a computational model. In the first group, a base case that represents normal esophageal transport and two hypothetical cases were simulated: (1) esophageal mucosa replaced by muscle and (2) esophagus without mucosa. For the base case, the geometric configuration of the esophageal wall was examined and the mechanical role of mucosa was analyzed. For the hypothetical cases, the pressure field and transport features were examined. In the second group of studies, cases with mucosa of varying stiffness were simulated. Overall transport characteristics were examined, and both pressure and geometry were analyzed. Results show that a compliant mucosa helped accommodate the incoming bolus and lubricate the moving bolus. Bolus transport was marginally achieved without mucosa or with mucosa replaced by muscle. A stiff mucosa greatly impaired bolus transport due to the lowered esophageal distensibility and increased luminal pressure. We conclude that mucosa is essential for normal esophageal transport function. Mechanically stiffened mucosa reduces the distensibility of the esophagus by obstructing luminal opening and bolus transport. Mucosal stiffening may be relevant in diseases characterized by reduced esophageal distensibility, elevated intrabolus pressure, and/or hypertensive muscle contraction such as eosinophilic esophagitis and jackhammer esophagus.

  18. Complete fundoplication is not associated with increased dysphagia in patients with abnormal esophageal motility.

    PubMed

    Heider, T R; Farrell, T M; Kircher, A P; Colliver, C C; Koruda, M J; Behrns, K E

    2001-01-01

    Abnormal esophageal motility is a relative contraindication to complete (360-degree) fundoplication because of a purported risk of postoperative dysphagia. Partial fundoplication, however, may be associated with increased postoperative esophageal acid exposure. Our aim was to determine if complete fundoplication is associated with increased postoperative dysphagia in patients with abnormal esophageal motor function. Medical records of 140 patients (79 females; mean age 48 +/- 1.1 years) who underwent fundoplication for gastroesophageal reflux disease (GERD) were reviewed retrospectively to document demographic data, symptoms, and diagnostic test results. Of the 126 patients who underwent complete fundoplication, 25 met manometric criteria for abnormal esophageal motility (#30 mm Hg mean distal esophageal body pressure or #80% peristalsis), 68 had normal esophageal function, and 33 had incomplete manometric data and were therefore excluded from analysis. Of the 11 patients who underwent partial fundoplication, eight met criteria for abnormal esophageal motility, two had normal esophageal function, and one had incomplete data and was therefore excluded. After a median follow-up of 2 years (range 0.5 to 5 years), patients were asked to report heartburn, difficulty swallowing, and overall satisfaction using a standardized scoring scale. Complete responses were obtained in 72%. Sixty-five patients who underwent complete fundoplication and had manometric data available responded (46 normal manometry; 19 abnormal manometry). Outcomes were compared using the Mann-Whitney U test. After complete fundoplication, similar postoperative heartburn, swallowing, and overall satisfaction were reported by patients with normal and abnormal esophageal motility. Likewise, similar outcomes were reported after partial fundoplication. This retrospective study found equally low dysphagia rates regardless of baseline esophageal motility; therefore a randomized trial comparing complete versus

  19. Lung alveolar epithelium and interstitial lung disease.

    PubMed

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic

    2009-01-01

    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  20. Viruses, Other Pathogenic Microorganisms and Esophageal Cancer

    PubMed Central

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

    2015-01-01

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

  1. Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

    ClinicalTrials.gov

    2015-12-18

    Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

  2. Airway epithelium stimulates smooth muscle proliferation.

    PubMed

    Malavia, Nikita K; Raub, Christopher B; Mahon, Sari B; Brenner, Matthew; Panettieri, Reynold A; George, Steven C

    2009-09-01

    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.

  3. Can esophageal dilation be avoided in the treatment of severe esophageal stricture caused by eosinophilic esophagitis?

    PubMed

    Silva, D; Santos, F; Piedade, S; Morais-Almeida, M

    2015-07-01

    Eosinophilic esophagitis (EoE) is an inflammatory immune-mediated disease with predominant eosinophilic inflammation characterized by the presence of esophageal dysfunction symptoms. Treatment delay can be associated with disease complications, like esophageal strictures, that can justify the use of invasive procedures which are not deprived of side effects. We present a case report of a 14 year old child with severe esophageal stricture secondary to EoE, that was treated with topical and systemic corticosteroid before any invasive procedure was considered. After 26 weeks of medical treatment, significant improvement of esophageal dysfunction occurred with histological remission and stricture resolution. In patients with severe esophageal strictures secondary to EoE, the need for esophageal dilation procedures should be considered only after anti-inflammatory treatment.

  4. Epidermization in the esophageal mucosa: unusual epithelial changes clearly detected by Lugol's staining.

    PubMed

    Nakanishi, Y; Ochiai, A; Shimoda, T; Yamaguchi, H; Tachimori, Y; Kato, H; Watanabe, H; Hirohashi, S

    1997-05-01

    A 58-year-old Japanese man with superficial esophageal cancer accompanied by unusual epithelial changes, including esophageal mucosal epidermization, is reported. Staining with Lugol's iodine clearly showed irregular unstained lesions, which could not be seen clearly macroscopically, in the resected specimen. Histologic examination of the irregular unstained areas showed definite granular and horny layers regarded as epidermization, acanthosis with slight nuclear enlargement, and epithelial atrophy. The immunohistochemical staining patterns of keratins in the epidermized and atrophic lesions were similar to those in the epidermis, and the keratin staining patterns of the acanthotic lesion were similar to those of the oral epithelium.

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

    PubMed Central

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

    2015-01-01

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

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

    SciTech Connect

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

    1982-10-01

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

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

    SciTech Connect

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

    1982-10-01

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

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

    PubMed Central

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

    2015-01-01

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

  9. Eosinophilic Esophagitis in Brazilian Pediatric Patients

    PubMed Central

    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

    2013-01-01

    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

  10. Esophageal Rupture as a Primary Manifestation in Eosinophilic Esophagitis

    PubMed Central

    Vernon, Natalia; Mohananey, Divyanshu; Ghetmiri, Ehsan; Ghaffari, Gisoo

    2014-01-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory process characterized by symptoms of esophageal dysfunction and, histologically, by eosinophilic infiltration of the esophagus. In adults, it commonly presents with dysphagia, food impaction, and chest or abdominal pain. Chronic inflammation can lead to diffuse narrowing of the esophageal lumen which may cause food impaction. Endoscopic procedures to relieve food impaction may lead to complications such as esophageal perforation due to the friability of the esophageal mucosa. Spontaneous transmural esophageal rupture, also known as Boerhaave's syndrome, as a primary manifestation of EoE is rare. In this paper, we present two adult patients who presented with esophageal perforation as the initial manifestation of EoE. This rare complication of EoE has been documented in 13 other reports (11 adults, 2 children) and only 1 of the patients had been previously diagnosed with EoE. A history of dysphagia was present in 1 of our patients and in the majority of previously documented patients. Esophageal perforation is a potentially severe complication of EoE. Patients with a history of dysphagia and patients with spontaneous esophageal perforation should warrant an evaluation for EoE. PMID:24899902

  11. Effect of gastroesophageal reflux on esophageal speech.

    PubMed

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

    1983-12-01

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

  12. Esophageal motility disorders: medical therapy.

    PubMed

    Lacy, Brian E; Weiser, Kirsten

    2008-01-01

    Symptoms of chest pain and dysphagia are common in the adult population. Most patients initially undergo an evaluation to exclude anatomic causes (ie, esophagitis, stricture) and cardiovascular disease as the etiology of these symptoms. Patients with persistent symptoms may then be referred for specialized testing of the esophagus, including esophageal manometry. Disorders of esophageal motility, which include achalasia, diffuse esophageal spasm, nutcracker esophagus, hypertensive lower esophageal sphincter, and ineffective motility are often identified in these patients. Unfortunately, the etiology of these disorders has not been well characterized and the treatment has not been standardized. This review will briefly discuss the impact, etiology, and diagnosis of esophageal motility disorders, and then focus on the medical management of these disorders using evidence from well-designed, prospective studies, where available.

  13. Ineffective esophageal motility is a primary motility disorder in gastroesophageal reflux disease.

    PubMed

    Ho, Shih-Chi; Chang, Chi-Sen; Wu, Chun-Ying; Chen, Gran-Hum

    2002-03-01

    The relationship between esophageal motor abnormalities and GERD has been widely studied. The purpose of this study was to identify the prevalence of ineffective esophageal motility (IEM) in patients with GERD. In addition, we also evaluated esophageal acid exposure, acid clearance, and endoscopic esophagitis in GERD patients with IEM. Of 89 patients enrolled in this study, 47 (52.8%) were found to have nonspecific esophageal motility disorder (NEMD). Forty-four of the 47 (93.6%) patients with NEMD met the diagnostic criteria for IEM. The overall incidence of IEM in GERD patients was 49.4%. Patients with IEM had significant increases in upright and recumbent mean fraction of time pH < 4 (6.70% and 4.38%) and mean recumbent esophageal acid clearance (12.45 min/reflux) when compared to those with other motility findings. Seventeen of the 44 (39%) IEM patients did not have endoscopic esophagitis. On the other hand, 26 of the 39 (67%) patients with normal manometry had endoscopic esophagitis. We concluded that not only is the prevalence of IEM high in GERD, but also that IEM patients have more recumbent gastroesophageal reflux and delayed acid clearance. Combined with endoscopic findings, we propose that IEM can be viewed as a specific entity of primary esophageal motility disorder in patients with GERD.

  14. Eosinophilic esophagitis in children with esophageal atresia.

    PubMed

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

    2014-01-01

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

  15. Abnormal Ion Permeation through Cystic Fibrosis Respiratory Epithelium

    NASA Astrophysics Data System (ADS)

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

    1983-09-01

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

  16. Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease.

    PubMed

    Cicala, Michele; Emerenziani, Sara; Guarino, Michele Pier Luca; Ribolsi, Mentore

    2013-10-21

    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.

  17. Esophageal Atresia and Tracheoesophageal Fistula

    MedlinePlus

    ... congenital abnormalities, cyanosis, esophageal atresia, fistula, gastroesophageal reflux disease, gastrointestinal defects, GERD, high alimentary tract obstruction, patent ductus arteriosus, pneumonia, polyhydramnios, tetralogy ...

  18. Eosinophilic esophagitis: current treatment.

    PubMed

    Redd, Matthew; Schey, Ron

    2013-03-01

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

  19. Mechanism of eosinophilic esophagitis.

    PubMed

    Mishra, Anil

    2009-02-01

    Eosinophilic esophagitis (EoE) is a newly recognized disease and is an emerging entity throughout developing and developed countries, including the United States. Therefore, understanding the causes, natural history, diagnosis, and management is important for future therapeutic interventions. The pathogenesis of EoE is still not clear, but a growing body of evidence has established that this condition represents a T-cell-mediated immune response involving several proinflammatory mediators and chemoattractants known to regulate eosinophilic accumulation in the esophagus, such as IL-4, IL-5, IL-3 and eotaxin-1, -2, and -3. Determining the mechanism or mechanisms through which human esophageal-derived factors ultimately induce the functional abnormalities observed, and to which antigens patients who have EoE are sensitized that lead to the manifestation of symptoms, is of significant interest.

  20. [Achalasia and esophageal cancer].

    PubMed

    Corti, R E; Monastra, L; Fernández Marty, P; Barco, J C; Ferro, F E; Galindo, F; Musi, A O; Kogan, Z

    1992-01-01

    During the period included between January 1970 and December 1990, we studied 242 patients with manometric and radiological diagnosis of esophageal achalasia. Eight of these patients (3.3%) developed during the evolution of their disease an esophageal carcinoma. Eight cases showed histologic type of epidermoid carcinoma: 3 differentiated, 3 semi-differentiated and 2 anaplastic. Therapy for achalasia was: one patient, Heller myotomy, 4 patients, dilatations with bougies in numerous opportunities, and the other two patients receive no treatment for achalasia. Two patients reported tracheobronchial fistulas as complication of carcinoma. Treatment received for carcinoma included: three patients, radiotherapy (4000 rads); one patient, chemotherapy; one patient, chemotherapy and radiotherapy, one resection surgery and two patients feeding gastrostomy. All of the eight patients died within the year of diagnosis of epidermoid carcinoma.

  1. [Giant esophageal fibrovascular polyp].

    PubMed

    Palacios, Fernando; Contardo, Carlos; Guevara, Jorge; Vera, Augusto; Aguilar, Luis; Huamán, Manuel; Palomino, Américo; Yabar, Alejandro

    2003-01-01

    Fibrovascular polyps are extremely rare benign neoplasias of the esophagus, which usually originate in the lower cricoid area. They do not produce any discomfort in the patient for a long time, however it may make itself evident by the patient's regurgitation of the polyp, producing asphyxia or, more frequently, dysphagia. The case of a 58 year old male patient is presented herein, with a 9 month record of dysphagia, weight loss and intermittent melena. The barium x-ray showed a distended esophagus, with a tumor running from the upper esophageal sphincter to the cardia. The endoscopy confirmed the presence of a pediculated tumor, implanted in the cervical esophagus. Surgeons suspected the potential malignancy of the tumor and performed a transhiatal esophagectomy. The final pathologic diagnosis was giant fibrovascular esophageal polyp.

  2. Fluorescence spectroscopy for diagnosis of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Panjehpour, Masoud; Overholt, Bergein F.; Vo-Dinh, Tuan; Farris, Christie; Schmidhammer, James L.; Sneed, Rick E.; Buckley, Paul F., III

    1994-07-01

    Laser-induced fluorescence spectroscopy was employed to measure fluorescence emission of normal and malignant tissue during endoscopy in patients with esophageal adenocarcinoma. A nitrogen/dye laser tuned at 410 nm was used for excitation source. The fluorescence lineshape of each spectrum was determined and sampled at 15 nm intervals from 430 nm to 716 nm. A calibration set from normal and malignant spectra were selected. Using stepwise discriminate analysis, significant wavelengths that separated normal and malignant spectra were selected. The intensities at these wavelengths were used to formulate a classification model using linear discriminate analysis. The model was used to classify additional tissue spectra from 26 malignant and 108 normal sites into either normal or malignant spectra with a sensitivity of 100 percent and specificity of 98 percent.

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

    PubMed

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

    2013-01-01

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

  4. Hypnotherapy for Esophageal Disorders.

    PubMed

    Riehl, Megan E; Keefer, Laurie

    2015-07-01

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

  5. The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

    PubMed

    Farmer, Adam D; Ruffle, James K; Aziz, Qasim

    2017-02-01

    The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

  6. Herpes simplex ulcerative esophagitis in healthy children.

    PubMed

    Al-Hussaini, Abdulrahman A; Fagih, Mosa A

    2011-01-01

    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.

  7. Prediction of esophageal and gastric histology by macroscopic diagnosis during upper endoscopy in pediatric celiac disease

    PubMed Central

    Boschee, Erin D; Yap, Jason Y K; Turner, Justine M

    2017-01-01

    AIM To determine the sensitivity of macroscopic appearance for predicting histological diagnosis at sites other than duodenum in pediatric celiac disease (CD). METHODS Endoscopic and histologic findings in pediatric patients undergoing upper endoscopy for first-time diagnosis of CD at Stollery Children’s Hospital from 2010-2012 were retrospectively reviewed. RESULTS Clinical charts from 140 patients were reviewed. Esophageal and gastric biopsies were taken in 54.3% and 77.9% of patients, respectively. Endoscopic appearance was normal in the esophagus and stomach in 75% and 86.2%. Endoscopic esophageal diagnoses were eosinophilic esophagitis (EE) (11.8%), esophagitis (7.9%), glycogenic acanthosis (1.3%) and non-specific abnormalities (3.9%). Endoscopic gastric diagnoses were gastritis (8.3%), pancreatic rest (0.9%), and non-specific abnormalities (4.6%). Histology was normal in 76.3% of esophageal and 87.2% of gastric specimens. Abnormal esophageal histology was EE (10.5%), esophagitis (10.5%), glycogenic acanthosis (1.3%) and non-specific (1.3%). Gastritis was reported in 12.8% of specimens. Sensitivity and specificity of normal endoscopy for predicting normal esophageal histology was 86.2% and 61.1%, and for normal gastric histology was 87.4% and 21.4%. CONCLUSION In the absence of macroscopic abnormalities, routine esophageal and gastric biopsy during endoscopy for pediatric CD does not identify major pathologies. These findings have cost and time saving implications for clinical practice. PMID:28216971

  8. [Epidermolysis bullosa acquisita complicated by esophageal stenosis. Endoscopic treatment with thermoplastic dilators and intralesional steroid injection].

    PubMed

    Moura, E G; Couto-Júnior, D S; Alvarado-Escobar, H; da Costa-Martins, B; Sallum, R A; Artifon, E L; Sakai, P

    2011-01-01

    Epidermolysis bullosa acquisita (EBA) is a rare auto-immune dermatologic disease, produced by auto-antibodies against colagen VII. We report a 44 years old male patient with EBA diagnosed 15 years before, who presented with progressive disphagia, being diagnosed an esophageal involvement of EBA. The patient was submitted to endoscopic treatment with thermoplastic bougie dilation and intralesional corticosteroid injection. The patient improved clinically with recovery of nutritional status. Esophageal involvement in EBA is very rare and its reason is still unknown. Endoscopic approach must be cautiously performed with the use of small diameter endoscopes, small caliber dilators, intralesional injection of corticosteroid and enteral tube in order to minimize the risks of complications, as well as esophageal rest from food trauma and better reparatory molding of the epithelium.

  9. Scanning electron microscopic studies of the surface morphology of the vomeronasal epithelium and olfactory epithelium of garter snakes.

    PubMed

    Wang, R T; Halpern, M

    1980-04-01

    Fixed vomeronasal and olfactory epithelia from normal adult garter snakes were microdissected, fractured, and examined with a scanning electron microscope. The method permits a detailed comparative study of the structural organization and morphological characteristics of the constituent cells of the vomeronasal and olfactory epithelia. Despite similarities in the nomenclature of the constituent cells in both epithelia, significant differences exist in their surface morphology. A unique columnar structure composed of non-neuronal elements is present in the vomeronasal epithelium. These columns house the bioplar neurons and undifferentiated cells. Such a columnar organization is absent in the olfactory epithelium. In vomeronasal epithelium the bipolar neurons possess microvillous terminals at their dendritic tips, while the dendritic tips of the bipolar neurons of the olfactory epithelium possess cilia. Vomeronasal supporting cells are covered with microvilli, while olfactory supporting cells are covered with cytoplasmic protuberances in addition to the microvilli. In the vomeronasal epithelium the pear-shaped neurons have a grossly smooth surface and are organized into clusters, while in the olfactory epithelium the elliptical bipolar neurons are spinous, aligned side-by-side and interdigitate. The basal (undifferentiated) cell layer in the vomeronasal epithelium has a high packing density and is composed of several layers of irregularly shaped cells. In the olfactory epithelium the basal cell layer is loosely organized and composed of a single layer of oval cells. This information on the three-dimensional cell structure of both epithelia provides a basis for experimental observations on changes in morphology of the bipolar neurons during genesis, development, maturation, degeneration, and regeneration in postnatal, adult animals.

  10. Esophageal motility disorders after gastric banding.

    PubMed

    O'Rourke, R W; Deveney, C W; McConnell, D B; Wolfe, B M; Jobe, B A

    2007-01-01

    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.

  11. Effluxing ABC Transporters in Human Corneal Epithelium

    PubMed Central

    Vellonen, Kati-Sisko; Mannermaa, Eliisa; Turner, Helen; Häkli, Marika; Wolosin, J. Mario; Tervo, Timo; Honkakoski, Paavo; Urtti, Arto

    2010-01-01

    ATP-binding cassette (ABC) transporters are able to efflux their substrate drugs from the cells. We compared expression of efflux proteins in normal human corneal epithelial tissue, primary human corneal epithelial cells (HCEpiC), and corneal epithelial cell culture model (HCE model) based on human immortal cell line. Expression of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1–6 (MRP1–6) and breast cancer resistance protein (BCRP) was studied using quantitative RT-PCR, Western blot, and immunohistochemistry. Only MRP1, MRP5, and BCRP were expressed in the freshly excised human corneal epithelial tissue. Expression of MRP1 and MRP5 was localized predominantly in the basal cells of the central cornea and limbus. Functional efflux activity was shown in the cell models, but they showed over-expression of most efflux transporters compared to that of normal corneal epithelium. In conclusion, MRP1, MRP5, and BCRP are expressed in the corneal epithelium, but MDR1, MRP2, MRP3, MRP4, and MRP6 are not significantly expressed. HCE cell model and commercially available primary cells deviate from this expression profile. PMID:19623615

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

    PubMed

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

    2007-12-01

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

  13. [Primary esophageal motility disorders; especially about esophageal achalasia].

    PubMed

    Miyazaki, Tatsuya; Sohda, Makoto; Sakai, Makoto; Tanaka, Naritaka; Suzuki, Shigemasa; Yokobori, Takehiko; Inose, Takanori; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kusano, Motoyasu; Kuwano, Hiroyuki

    2011-07-01

    Esophageal motility disorders are classified primary and secondary, and primary esophageal motility disorders are classified esophageal achalasia and other diseases by manometry. An esophageal emptying disorder associated with insufficient relaxation of the lower esophageal sphincter (LES) and elimination of peristaltic waves on the esophageal body is the major abnormality of achalasia. Esophagogram, endoscopy, and manometry are used for diagnosis. As pharmacological therapy, administration of a calcium channel blocker or nitrate is useful. The pharmacological therapy is not recommended as long-term basic therapy but as a temporary treatment. At 1st, the balloon dilation method is chosen in treatment of achalasia Surgical treatment is indicated in the following cases: (1) Patients uneffected by balloon dilation, (2) Flask type with grade II to III dilation, and sigmoid type, (3) the gradual progression to the pathophysiological stage, (4) young patients, (5) complicated with esophageal cancer. Laparoscopic Heller-Dor procedure is the most popular surgical procedure, recently. It is somewhat difficult to perform surgical treatment for this functional disease. We should select the most suitable individualized treatment with efficient comprehension of the pathophysiological situation.

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

    SciTech Connect

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

    1981-05-01

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

  15. Radiation Therapy for Locally Advanced Esophageal Cancer.

    PubMed

    Chun, Stephen G; Skinner, Heath D; Minsky, Bruce D

    2017-04-01

    The treatment of locally advanced esophageal cancer is controversial. For patients who are candidates for surgical resection, multiple prospective clinical trials have demonstrated the advantages of neoadjuvant chemoradiation. For patients who are medically inoperable, definitive chemoradiation is an alternative approach with survival rates comparable to trimodality therapy. Although trials of dose escalation are ongoing, the standard radiation dose remains 50.4 Gy. Modern radiotherapy techniques such as image-guided radiation therapy with motion management and intensity-modulated radiation therapy are strongly encouraged with a planning objective to maximize conformity to the intended target volume while reducing dose delivered to uninvolved normal tissues.

  16. Fungal Esophagitis Presenting With Esophagitis Dissecans Superficialis: Cause or Concurrence? A Diagnostic Conundrum

    PubMed Central

    Patil, Rashmee; Sunkara, Tagore; Ona, Mel A.; Gaduputi, Vinaya; Reddy, Madhavi

    2016-01-01

    Esophagitis dissecans superficialis (EDS) is a rare desquamative disorder of the esophagus. It is characterized by sheets of sloughed squamous tissue with normal underlying mucosa. We present a case of a 68-year-old man with severe anemia and a positive fecal occult blood test who was found to have features suggestive of EDS during endoscopy. However, histological features were suggestive of both EDS and fungal esophagitis. To our knowledge, this is the first reported case in literature which discusses the clinical scenario of fungal infection being a possible etiology rather than a commonly accepted differential diagnosis of EDS. We also review the clinical features, diagnostic criteria and treatment of EDS. PMID:28058081

  17. Structural changes in rabbit oral epithelium caused by zinc deficiency.

    PubMed

    Joseph, C E; Ashrafi, S H; Waterhouse, J P

    1981-01-01

    We report the successful establishment of zinc deficiency in rabbits by dietary means. The soybean protein of a standard rabbit diet was replaced by egg albumin. Weanling, New Zealand white rabbits, were fed a low zinc diet containing 1.5 microgram Zn/g of diet. Zinc-deficient rabbits showed stunted growth, weight loss, altered posture, partial alopecia and crusting of skin. Structural alterations in oral epithelium of the zinc-deficient rabbits included in the tongue flattened filiform papillae showing parakeratosis, in the cheek parakeratosis of the normally nonkeratinized epithelium and hyperplasia of the lip epidermis.

  18. Metabolic competence and susceptibility of intestinal epithelium to genotoxic injury during regeneration.

    PubMed

    Patel, H R; Hewer, A; Phillips, D H; Hayes, J D; Wolf, C R; Campbell, F C

    1997-11-01

    The carcinogenic potency of many mutagens is increased in conditions of tissue regeneration. This involves fundamental changes of cellular division and differentiation, in intestinal epithelium. However, effects on epithelial capacity for carcinogen metabolism and susceptibility to genotoxic injury are unknown. Using a novel rat model, this study assessed expression of cytochrome P450 mono-oxygenases (Cyps), glutathione S-transferases (GSTs) and uridine diphosphoglucuronosyl transferase (UGT) in intestinal epithelium during sequential stages of regeneration. Enzyme induction and DNA adduct formation were also assessed after benzo[a]pyrene (BaP) exposure. Control assays were carried out in normal intestinal epithelium. Fewer phase I and II xenobiotic metabolizing enzymes were expressed in regenerating intestinal epithelium than in normal control intestinal epithelium (GSTA3, UGT in regeneration vs Cyp2B, GSTA1/2, GSTA4, GSTP1, UGT in control). Benzo[a]pyrene induced GSTA3 and UGT in regeneration vs Cyp1A, Cyp2B, GSTA1/2, GSTA3, GSTA4, GSTP1 and UGT in control normal intestinal epithelium. Benzo[a]pyrene induced low levels of GSTA3 in early regenerating intestinal epithelium but induction increased by >2-fold at late stage regeneration. Higher levels of benzo[a]pyrene 7,8-diol-9,10-epoxide (BPDE) DNA adducts were formed at early stages of regeneration, than at later stages. Intestinal epithelium displayed reduced metabolic competence and differential susceptibility to genotoxic injury from BaP, during regeneration.

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

    PubMed

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

    2016-01-01

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

  20. Treatment of advanced esophageal cancer

    SciTech Connect

    Kelsen, D.

    1982-12-01

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

  1. Acid corrosive esophagitis: radiographic findings.

    PubMed

    Muhletaler, C A; Gerlock, A J; de Soto, L; Halter, S A

    1980-06-01

    Thirty-nine esophagograms of 24 patients after ingestion of muriatic acid (27% HCI) in suicide attempts were reviewed. All esophagograms were obtained in the acute, subacute, and chronic phases. In the acute and subacute phases, the radiographic findings consisted of mucosal edema, submucosal edema or hemorrhage, ulcerations, sloughing of the mucosa, atony, and dilatation. Strictures of the esophagus were present in the chronic phase. These radiographic findings were not different from those found in alkaline corrosive esophagitis. The severity of the corrosive esophagitis is considered related to the concentration, amount, viscosity, and duration of contact between the caustic agent and the esophageal mucosa.

  2. Nuclear medicine and esophageal surgery

    SciTech Connect

    Taillefer, R.; Beauchamp, G.; Duranceau, A.C.; Lafontaine, E.

    1986-06-01

    The principal radionuclide procedures involved in the evaluation of esophageal disorders that are amenable to surgery are illustrated and briefly described. The role of the radionuclide esophagogram (RE) in the diagnosis and management of achalasia, oculopharyngeal muscular dystrophy and its complications, tracheoesophageal fistulae, pharyngeal and esophageal diverticulae, gastric transposition, and fundoplication is discussed. Detection of columnar-lined esophagus by Tc-99m pertechnetate imaging and of esophageal carcinoma by Ga-67 citrate and Tc-99m glucoheptonate studies also is presented. 37 references.

  3. Esophageal Lipoma: A Rare Tumor

    PubMed Central

    Feldman, Jeremy; Tejerina, Manfred; Hallowell, Michael

    2012-01-01

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

  4. Primary esophageal mucosa-associated lymphoid tissue lymphoma

    PubMed Central

    Ma, Qiang; Zhang, Chun; Fang, San’gao; Zhong, Peng; Zhu, Xiangfeng; Lin, Li; Xiao, Hualiang

    2017-01-01

    Abstract Rationale: Mucosa-associated lymphoid tissue (MALT) lymphoma is a low grade malignant B cell lymphoma which occurs mainly in the organs having mucosal layer. Though gastrointestinal tract is the most commonly involved extranodal site, primary esophageal MALT lymphoma is very rare with less than 20 cases reported in literature. Patient concerns: A 75-year-old man was referred to our hospital for evaluation of dysphagia. Endoscopy revealed a submucosal tumor located in the middle and lower third of esophagus. CT chest and endoscopic ultrasound revealed a 15.5 × 5.9 × 4.0 cm well circumscribed submucosa esophageal tumor. Test for serum antibody against H. pylori was negative. Due to the large tumor size, patient underwent surgical resection. Histological examination showed a submucosal tumor consisting of multiple nodules of varying sizes with intact covering squamous epithelium. The nodules were mainly composed of diffusely and monoclonal proliferating centrocyte-like or monocyte-like cells. Follicular colonizations were observed without lymphoepithelial lesions. The tumor cells were diffusely positive for CD20, PAX-5, Bcl-2 and follicular dendritic cells were positive for CD21, CD23. Monoclonal gene rearrangement was positive for immunoglobulin heavy chain gene, Kappa light chain gene and Lambda light chain gene. Diagnoses: Based on these findings, final diagnosis of esophageal MALT lymphoma was made. Outcomes: At 8 month follow up, no recurrence or metastases was detected. Lessons: Esophageal MALT lymphoma is a rare disease with definitive diagnosis possible only after histopathological examination. It carries good prognosis due to low malignant potential. PMID:28353588

  5. Esophageal squamous papillomas with focal dermal hypoplasia and eosinophilic esophagitis

    PubMed Central

    Pasman, Eric A; Heifert, Theresa A; Nylund, Cade M

    2017-01-01

    Focal dermal hypoplasia (FDH) is a rare disorder of the mesodermal and ectodermal tissues. Here we present an eight-year-old female known to have FDH who presents with poor weight gain and dysphagia. She was diagnosed with multiple esophageal papillomas and eosinophilic esophagitis. She was successfully treated with argon plasma coagulation and ingested fluticasone propionate, which has not been described previously in a child.

  6. Epigenetic Regulation of the Intestinal Epithelium

    PubMed Central

    Elliott, Ellen N.; Kaestner, Klaus H.

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-03-01

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

  9. Environmental Causes of Esophageal Cancer

    PubMed Central

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

    2009-01-01

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

  10. Drugs Approved for Esophageal Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for esophageal cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  11. Caustic ingestion and esophageal function

    SciTech Connect

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

    1990-02-01

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

  12. Treatment Option Overview (Esophageal Cancer)

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  13. General Information about Esophageal Cancer

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  14. Esophageal pH monitoring

    MedlinePlus

    ... test can also be done during upper GI endoscopy by clipping a pH monitor to the lining of the esophagus. ... esophagitis : Barium swallow Esophagogastroduodenoscopy (also called upper GI endoscopy)

  15. Radiation-induced esophagitis in lung cancer

    PubMed Central

    Baker, Sarah; Fairchild, Alysa

    2016-01-01

    Radiation-induced esophagitis is the most common local acute toxicity of radiotherapy (RT) delivered for the curative or palliative intent treatment of lung cancer. Although concurrent chemotherapy and higher RT dose are associated with increased esophagitis risk, advancements in RT techniques as well as adherence to esophageal dosimetric constraints may reduce the incidence and severity. Mild acute esophagitis symptoms are generally self-limited, and supportive management options include analgesics, acid suppression, diet modification, treatment for candidiasis, and maintenance of adequate nutrition. Esophageal stricture is the most common late sequela from esophageal irradiation and can be addressed with endoscopic dilatation. Approaches to prevent or mitigate these toxicities are also discussed. PMID:28210168

  16. Uses of esophageal function testing: dysphagia.

    PubMed

    Yazaki, Etsuro; Woodland, Philip; Sifrim, Daniel

    2014-10-01

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

  17. Eosinophilic esophagitis: strictures, impactions, dysphagia.

    PubMed

    Khan, Seema; Orenstein, Susan R; Di Lorenzo, Carlo; Kocoshis, Samuel A; Putnam, Philip E; Sigurdsson, Luther; Shalaby, Theresa M

    2003-01-01

    Eosinophilic esophagitis, long known to be a feature of acid reflux, has recently been described in patients with food allergies and macroscopically furrowed esophagus. The pathophysiology and optimal management of patients with eosinophilic esophagitis is unclear. We describe our clinical experience related to eosinophilic esophagitis and obstructive symptoms in children and propose etiopathogenesis and management guidelines. Twelve children with obstructive esophageal symptoms (11 male), median age 5 years, and identified to have eosinophilic esophagitis with > 5 eosinophils per high-power field (eos/hpf) are reported. Of these, four had strictures, six had impactions, and two had only dysphagia. A diagnostic evaluation included esophagogastroduodenoscopy with biopsies in all and upper gastrointestinal series, IgE, radioallergosorbent tests, and skin tests for food allergies in some cases. Esophageal histology specimens were independently analyzed for eosinophil density by two authors. Four of five children with > 20 eos/hpf responded to elimination diets/steroids. The fifth child responded to a fundoplication. Seven children had 5-20 eos/hpf and three of them with no known food allergies responded to antireflux therapy alone. Three others in this group with positive food allergies responded to treatment with elimination diets and/or steroids. The seventh patient in this group was lost to follow-up. In conclusion, on the basis of response to therapy, eosinophilic esophagitis can be subdivided into two groups: those with likely gastroesophageal reflux disease if < 20 eos/hpf and no food allergies, and others with allergic eosinophilic esophagitis associated with food allergies and often with > 20 eos/hpf.

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

    PubMed

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

    2012-04-07

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

  19. Esophageal space-occupying lesion caused by Ascaris lumbricoides

    PubMed Central

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

    2012-01-01

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

  20. Relationship between COX-2 and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma

    PubMed Central

    Huang, Jun-Xing; Xiao, Wei; Chen, Wei-Chang; Lin, Mao-Song; Song, Zheng-Xiang; Chen, Ping; Zhang, Yun-Lei; Li, Feng-Yue; Qian, Rong-Yu; Salminen, Eeva

    2010-01-01

    AIM: To investigate the correlation between cyclooxygenase-2 (COX-2) and cell cycle-regulatory proteins in patients with esophageal squamous cell carcinoma (ESCC). METHODS: One hundred and two surgically obtained specimens of ESCC were randomly collected. All specimens were obtained from patients who had not received chemo- or radiotherapy prior to surgical resection. Twenty-eight specimens of normal squamous epithelium served as controls. The expression of COX-2, Ki-67, cyclin A and p27 was examined by immunohistochemistry. The Pearson test was used to analyze the relationship between groups. RESULTS: The protein level of COX-2, Ki-67 and cyclin A was significantly higher in ESCC than in normal squamous epithelium (74.7 ± 61.2 vs 30.2 ± 43.4, 64.0 ± 51.6 vs 11.6 ± 2.3, 44.2 ± 32.2 vs 11.7 ± 5.0, respectively, all P < 0.01). In contrast, the protein level of p27 was significantly lower in ESCC than in normal squamous epithelium (182.0 ± 69.0 vs 266.4 ± 28.0, P < 0.01). In ESCC, COX-2 expression was correlated with T stage, the score of T1-T2 stage was lower than that of T3-T4 stage (55.0 ± 42.3 vs 83.0 ± 66.5, P < 0.05), and Ki-67, cyclin A and p27 expressions were correlated with the tumor differentiation (43.8 ± 31.7 vs 98.4 ± 84.8, 32.0 ± 19.0 vs 54.1 ± 53.7, 206.2 ± 61.5 vs 123.5 ± 68.3, respectively, all P < 0.01). COX-2 expression was positively correlated to Ki-67, cyclin A and negatively correlated to p27 expression in ESCC (r = 0.270, 0.233 and -0.311, respectively, all P < 0.05). CONCLUSION: The expression of COX-2 is correlated with tumor cell invasion and is closely related to the cell proliferation in patients with ESCC. PMID:21157974

  1. Esophageal malignancy: A growing concern

    PubMed Central

    Chai, Jianyuan; Jamal, M Mazen

    2012-01-01

    Esophageal cancer is mainly found in Asia and east Africa and is one of the deadliest cancers in the world. However, it has not garnered much attention in the Western world due to its low incidence rate. An increasing amount of data indicate that esophageal cancer, particularly esophageal adenocarcinoma, has been rising by 6-fold annually and is now becoming the fastest growing cancer in the United States. This rise has been associated with the increase of the obese population, as abdominal fat puts extra pressure on the stomach and causes gastroesophageal reflux disease (GERD). Long standing GERD can induce esophagitis and metaplasia and, ultimately, leads to adenocarcinoma. Acid suppression has been the main strategy to treat GERD; however, it has not been proven to control esophageal malignancy effectively. In fact, its side effects have triggered multiple warnings from regulatory agencies. The high mortality and fast growth of esophageal cancer demand more vigorous efforts to look into its deeper mechanisms and come up with better therapeutic options. PMID:23236223

  2. Increased expression of nestin in human pterygial epithelium

    PubMed Central

    Wen, Dan; Wang, Hua; Heng, Boon Chin; Liu, Hua

    2013-01-01

    AIM To investigate the distribution of nestin-positive cells in pterygium, as well as the relationship between nestin-positive cells and proliferative cells in the pathogenesis of pterygium. METHODS Nine pterygium specimens and 5 normal conjunctiva specimens were investigated. All explanted specimens were immediately immersed in 5-Ethynyl-2′-deoxyuridine, and were subjected to hematoxylin and eosin staining, as well as immunostaining to detect nestin. RESULTS Small sub-populations of nestin-expressing cells in both normal and pterygial conjunctiva epithelium were found. These were located at the superficial layer of the epithelium, and were significantly increased (P=0.007) and spread out in the pterygial conjunctiva epithelium, even though these cells were mitotically quiescent. CONCLUSION In pterygium, more nestin-positive cells were present at the superficial layer of the epithelium. With growing scientific evidence that nestin plays an important role in defining various specialized cell types, such as stem cells, cancer cells and angiogenic cells, further investigations on the roles of nestin-expressing cells in pterygium may help to uncover the mechanisms of initiation, development and the prognosis of this disease. PMID:23826515

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

    PubMed

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

    2016-01-01

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

  4. Chicago Classification Criteria of Esophageal Motility Disorders Defined in High Resolution Esophageal Pressure Topography (EPT)†

    PubMed Central

    Bredenoord, Albert J; Fox, Mark; Kahrilas, Peter J; Pandolfino, John E; Schwizer, Werner; Smout, AJPM; Conklin, Jeffrey L; Cook, Ian J; Gyawali, Prakash; Hebbard, Geoffrey; Holloway, Richard H; Ke, Meiyun; Keller, Jutta; Mittal, Ravinder K; Peters, Jeff; Richter, Joel; Roman, Sabine; Rommel, Nathalie; Sifrim, Daniel; Tutuian, Radu; Valdovinos, Miguel; Vela, Marcelo F; Zerbib, Frank

    2011-01-01

    Background The Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high resolution esophageal pressure topography (EPT) studies, concurrent with the widespread adoption of this technology into clinical practice. The Chicago Classification has been, and will continue to be, an evolutionary process, molded first by published evidence pertinent to the clinical interpretation of high resolution manometry (HRM) studies and secondarily by group experience when suitable evidence is lacking. Methods This publication summarizes the state of our knowledge as of the most recent meeting of the International High Resolution Manometry Working Group in Ascona, Switzerland in April 2011. The prior iteration of the Chicago Classification was updated through a process of literature analysis and discussion. Key Results The major changes in this document from the prior iteration are largely attributable to research studies published since the prior iteration, in many cases research conducted in response to prior deliberations of the International High Resolution Manometry Working Group. The classification now includes criteria for subtyping achalasia, EGJ outflow obstruction, motility disorders not observed in normal subjects (Distal esophageal spasm, Hypercontractile esophagus, and Absent peristalsis), and statistically defined peristaltic abnormalities (Weak peristalsis, Frequent failed peristalsis, Rapid contractions with normal latency, and Hypertensive peristalsis). Conclusions & Inferences The Chicago Classification is an algorithmic scheme for diagnosis of esophageal motility disorders from clinical EPT studies. Moving forward, we anticipate continuing this process with increased emphasis placed on natural history studies and outcome data based on the classification. PMID:22248109

  5. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  6. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  7. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  8. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  9. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  10. Computer analysis of radionuclide esophageal transit studies

    SciTech Connect

    Klein, H.A.; Wald, A.

    1984-09-01

    For detailed examination of the esophageal transit of a swallowed radioactive liquid bolus, three computer-based techniques have been developed: analysis of time-activity curves with decomposition into rapid and residual components, yielding the mean transit time for the former and the residual fraction for the latter; reduction of dynamic image sequences to single condensed images, facilitating subjective assessment; and tracking of the centroid of radioactivity, permitting quantification of retrograde motion. Studies were performed on 12 normal subjects and on six patients with motility disorders. Elevated residual fractions were observed in all the patients, and an abnormal degree of retrograde motion in two. Two normal and two abnormal studies exemplify the variety of patterns observed in condensed images.

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

    PubMed Central

    Wen, Jing; Lu, Zhongsheng; Liu, Qingsen

    2014-01-01

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

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

    PubMed

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

    2004-01-01

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

  13. Rare tumors of esophageal squamous mucosa.

    PubMed

    Tripathi, Monika; Swanson, Paul E

    2016-10-01

    In spite of increasing incidence of esophageal adenocarcinoma in the last few decades, esophageal squamous cell carcinoma (SCC) still remains the dominant subtype of esophageal cancer worldwide. Apart from conventional SCC, some rare unconventional tumors of esophageal squamous mucosa are also well known. This study provides an introduction to these and presents a brief review of the literature, including the diagnostic and prognostic importance of each variant.

  14. Gallium-67 imaging in candidal esophagitis

    SciTech Connect

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

    1990-01-01

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

  15. [Diagnosis and management of esophageal chest pain].

    PubMed

    Hong, Su Jin

    2010-04-01

    Esophageal pain that manifests as heartburn or chest pain, is a prevalent problem. Esophageal chest pain is most often caused by gastroesophageal reflux disease (GERD), but can also result from inflammatory processes, infections involving the esophagus, and contractions of the esophageal muscle. The mechanisms and pathways of esophageal chest pain are poorly understood. Vagal and spinal afferent pathways carry sensory information from the esophagus. Recently, esophageal hypersensitivity is identified as an important factor in the development of esophageal pain. A number of techniques are available to evaluate esophageal chest pain such as endoscopy and/or proton-pump inhibitor trial, esophageal manometry, a combined impedance-pH study, and esophageal ultrasound imaging. Proton pump inhibitors (PPIs) have the huge success in the treatment of GERD. Other drugs such as imipramine, trazadone, sertraline, tricyclics, and theophylline have been introduced for the control of esophageal chest pain in partial responders to PPI and the patients with esophageal hypersensitivity. Novel drugs which act on different targets are anticipated to treat esophageal pain in the future.

  16. Glucose metabolism in rat retinal pigment epithelium.

    PubMed

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

    2006-01-01

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

  17. Human esophageal response during chest pain induced by swallowing cold liquids.

    PubMed

    Meyer, G W; Castell, D O

    1981-11-06

    Normal persons often note chest or back pain during rapid ingestion of cold liquids, commonly believed to result from cold-induced "spasm" of esophageal muscle. We studied the effects of swallowing cold liquids on esophageal function in five normal subjects, aged 20 to 44 years, by comparing their response to cold ice cream (-5 degrees C) and room temperature ice cream mix (20 degrees C). Decreased peristaltic amplitude was seen during cold ice cream ingestion, primarily in the midesophagus. When seven subjects rapidly ingested ice cream until chest pain was produced and maintained for at least 60 s, complete absence of motor activity in the distal esophagus occurred, with slow return to normal during the ensuing five minutes. Our studies indicate that ingestion of cold liquids significantly depresses peristaltic amplitudes and frequency of peristalsis in normal persons, and pain is associated with complete absence of motor activity in the body of the esophagus, rather than esophageal "spasm" as commonly believed.

  18. [Esophageal diseases: GERD, Barrett, achalasia and eosinophilic esophagitis].

    PubMed

    Calvet, Xavier; Villoria, Albert

    2014-09-01

    At Digestive Disease Week (DDW) 2014, developments in esophageal disease were presented. Highlights include: the usefulness of impedancemetry to diagnose reflux disease, or the effectiveness of PPIs for treating non-cardiac chest pain. Concerning Barrett's esophagus, its prevalence is identical in patients with and without reflux symptoms, Barrett segments less than 1cm probably do not require follow-up, and in older patients with long-segment Barrett, initial endoscopies overlooked up to 2% of significant lesions. Regarding achalasia, surgical myotomy is no more effective than endoscopic dilation and may even be less effective than peroral endoscopic myotomy (POEM). In terms of eosinophilic esophagitis, it is important to systematically take biopsies in patients with dysphagia so that cases of eosinophilic esophagitis are not overlooked. In addition, for this condition, routine endoscopic dilations not only do not seem useful in improving the course of the disease, but could also worsen the response to medical treatment.

  19. Differential role of FGF9 on epithelium and mesenchyme in mouse embryonic lung.

    PubMed

    del Moral, Pierre-Marie; De Langhe, Stijn P; Sala, Frédéric G; Veltmaat, Jacqueline M; Tefft, Denise; Wang, Kasper; Warburton, David; Bellusci, Savério

    2006-05-01

    Mesothelial Fibroblast Growth Factor 9 (Fgf9) has been demonstrated by inactivation studies in mouse to be critical for the proliferation of the mesenchyme. We now show that Fgf9 is also expressed at significant levels in the distal epithelium from the mid-pseudoglandular stages. Using mesenchymal-free lung endoderm culture, we show that FGF9 triggers the proliferation of the distal epithelium leading to the formation of a cyst-like structure. On embryonic Fgfr2b-/- lungs, FGF9 induces proliferation of the mesenchyme but fails to trigger a similar effect on the epithelium, therefore involving the FGFR2b receptor in the proliferative response of the epithelium to FGF9. While FGF9 inhibits the differentiation of the mesenchyme, the epithelium appears to differentiate normally. At the molecular level, FGF9 up-regulates Fgf10 expression in the mesenchyme likely via increased expression of Tbx4 and 5 and controls the transcription of Hedgehog targets Ptc and Gli-1 in a Hedgehog-independent manner. We also show that FGF9 inhibits the activation of the canonical Wnt pathway in the epithelium by increasing Dkk1 expression, a canonical Wnt antagonist. Our work shows for the first time that FGF9 acts on the epithelium involving FGFR2b to control its proliferation but not its differentiation and contributes to the regulation of canonical Wnt signaling in the epithelium.

  20. Eosinophilic esophagitis in an octogenarian

    PubMed Central

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

    2016-01-01

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

  1. Esophageal thermal injury by hot adlay tea.

    PubMed

    Go, Hoon; Yang, Hyeon Woong; Jung, Sung Hee; Park, Young A; Lee, Jung Yun; Kim, Sae Hee; Lim, Sin Hyung

    2007-03-01

    Reversible thermal injury to the esophagus as the result of drinking hot liquids has been reported to generate alternating white and red linear mucosal bands, somewhat reminiscent of a candy cane. This phenomenon is associated with chest pain, dysphagia, odynophagia, and epigastric pain. Here, we report a case of thermal injury to the esophageal and oral cavity due to the drinking of hot tea, including odynophagia and dysphagia. A 69-year-old man was referred due to a difficulty in swallowing which had begun a week prior to referral. The patient, at the time of admission, was unable to swallow even liquids. He had recently suffered from hiccups, and had consumed five cups of hot adlay tea one week prior to admission, as a folk remedy for the hiccups. Upon physical examination, the patient's oral cavity evidenced mucosal erosion, hyperemia, and mucosa covered by a whitish pseudomembrane. Nonspecific findings were detected on the laboratory and radiological exams. Upper endoscopy revealed diffuse hyperemia, and erosions with thick and whitish pseudomembraneous mucosa on the entire esophagus. The stomach and duodenum appeared normal. We diagnosed the patient with thermal esophageal injury inflicted by the hot tea. He was treated with pantoprazole, 40 mg/day, for 14 days, and evidenced significant clinical and endoscopic improvement.

  2. The expression and clinical significance of metastasis suppressor gene and matrix metalloproteinase-2 in esophageal squamous cell of carcinoma.

    PubMed

    Guo, Xiao-Qi; Li, Xing-Ya

    2016-07-01

    To investigate the expression and clinical significance of metastasis suppressor gene and matrix metalloproteinase-2 in esophageal squamous cell of carcinoma. choose 30 cases of specimens of esophageal squamous cell carcinoma which are removed in surgery and confirmed by pathology and 30 cases of specimens of normal esophageal mucosa. Use immunohistochemistry SP method to detect the expression of nm23-H1, MMP-2 protein in esophageal squamous cell carcinoma and normal esophageal mucosal. The positive rate of nm23-H1 protein in esophageal squamous cell carcinoma was 43.3% (13/30), while that in normal esophageal mucosa was 100% (30/30), which has a significant difference between them (χ2=22. 083, P<0.05). The positive rate of MMP-2 protein in esophageal squamous cell carcinoma was 90.0% (27/30), while that in normal esophageal mucosa was 33.3% (10/30), and there is a significant difference between them (χ2=28. 370, P<0.05); For the expression of nm23-H1 and MMP-2 in esophageal squamous cell carcinoma, there was nothing to do with sex, age and tumor size (P>0.05), but it was related to the degree of tumor differentiation, depth of invasion and lymph node metastasis (P<0.05); The expression of nm23-H1 is related to the cut end of residual cancer (P<0.05), while the expression of MMP-2 has nothing to do with the cut end of residual cancer (P>0.05); The expression of nm23-H1 and MMP-2 in esophageal squamous cell carcinoma was negatively correlated. nm23-H1 and MMP-2 have played a role in the development of esophageal cancer, which can promote the occurence of distant metastasis; The loss of expression of nm23-H1 may be related to cut end residual cancer; nm23-H1 and MMP-2 may be as an indicator for esophageal cancer metastasis and prognosis.

  3. Surgical treatments for esophageal cancers

    PubMed Central

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

    2015-01-01

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

  4. Calpain-14 and its association with eosinophilic esophagitis.

    PubMed

    Litosh, Vladislav A; Rochman, Mark; Rymer, Jeffrey K; Porollo, Aleksey; Kottyan, Leah C; Rothenberg, Marc E

    2017-01-25

    Calpains are a family of intracellular, calcium-dependent cysteine proteases involved in a variety of regulatory processes, including cytoskeletal dynamics, cell-cycle progression, signal transduction, gene expression, and apoptosis. These enzymes have been implicated in a number of disease processes, notably for this review involving eosinophilic tissue inflammation, such as eosinophilic esophagitis (EoE), a chronic inflammatory disorder triggered by allergic hypersensitivity to food and associated with genetic variants in calpain 14 (CAPN14). Herein we review the genetic, structural, and biochemical properties of CAPN14 and its gene product CAPN14, and its emerging role in patients with EoE. The CAPN14 gene is localized at chromosome 2p23.1-p21 and is most homologous to CAPN13 (36% sequence identity), which is located 365 kb downstream of CAPN14. Structurally, CAPN14 has classical calpain motifs, including a cysteine protease core. In comparison with other human calpains, CAPN14 has a unique expression pattern, with the highest levels in the upper gastrointestinal tract, particularly in the squamous epithelium of the esophagus. The CAPN14 gene is positioned in an epigenetic hotspot regulated by IL-13, a TH2 cytokine with increased levels in patients with EoE that has been shown to be a mediator of the disease. CAPN14 induces disruptive effects on the esophageal epithelium by impairing epithelial barrier function in association with loss of desmoglein-1 expression and has a regulatory role in repairing epithelial changes induced by IL-13. Thus CAPN14 is a unique protease with distinct tissue-specific expression and function in patients with EoE and is a potential therapeutic target for EoE and related eosinophilic and allergic diseases.

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

    PubMed Central

    Truskaite, Kotryna

    2016-01-01

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

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

    PubMed

    Truskaite, Kotryna; Dlugosz, Aldona

    2016-01-01

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

  7. [Exfoliative esophagitis while taking dabigatran].

    PubMed

    Scheppach, Wolfgang; Meesmann, Malte

    2015-04-01

    History | A 77-year-old woman was admitted with severe chest pain, heartburn, dysphagia and odynophagia. She had been on dabigatran for 13 months due to atrial fibrillation and arterial hypertension. Investigations and findings | Endoscopy of the esophagus revealed sloughing of mucosal casts, predominantly in the upper half of the organ. Treatment and course | The patient was placed on pantoprazol, local anaesthetic antacid and i. v. fluids. Dabigatran was discontinued. The symptoms disappeared within 3 days. Control endoscopy after 12 days showed complete healing of the esophageal mucosa. Conclusion | The intake of dabigatran was associated with exfoliative esophagitis, possibly due to caustic tissue damage by prolonged drug contact.

  8. Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms

    PubMed Central

    Jiang, Liuqin; Ye, Bixing; Wang, Ying; Wang, Meifeng; Lin, Lin

    2017-01-01

    Background/Aims Little data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). Methods We retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. Results Forty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group (P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. Conclusions IEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients. PMID:27599539

  9. Utility of ambulatory 24-hour esophageal pH and motility monitoring in noncardiac chest pain: report of 90 patients and review of the literature.

    PubMed

    Lacima, Gloria; Grande, Luis; Pera, Manuel; Francino, Antonio; Ros, Emilio

    2003-05-01

    It is unclear whether prolonged motility monitoring improves the diagnostic yield of standard esophageal tests in patients with noncardiac chest pain. Our aim was to assess the diagnostic value of ambulatory 24-hr pH and pressure monitoring in patients with noncardiac chest pain. Stationary manometry, edrophonium testing, and ambulatory pH and motility studies were performed in 90 consecutive patients with recurrent chest pain and normal coronary angiograms. Normality limits of ambulatory 24-hr motility were established in 30 healthy controls. The diagnoses of specific esophageal motility disorders (nutcracker esophagus and diffuse esophageal spasm) by stationary and ambulatory manometry were discordant in 48% of the patients. Edrophonium testing was positive in 9 patients, but correlated poorly with esophageal diagnoses. During ambulatory studies, 144 chest pain events occurred in 42 patients, and 72 (50%) were related to esophageal dysfunction. Strict temporal associations of events with esophageal dysfunction in relation to ambulatory 24-hr pH/motility scores permitted four patient categorizations: true positives (event-related and abnormal tests), N = 15; true negatives (event-unrelated and abnormal tests), N = 10; reduced esophageal pain threshold (event-related and normal tests), N = 4; and indeterminate origin (event-unrelated and normal tests), N = 13. Overall, 19 patients (21%) had a probable esophageal cause for chest pain (14 esophageal motility disorder, 4 acid reflux, 1 both). In conclusion, ambulatory manometry increases the diagnostic yield of standard esophageal testing in noncardiac chest pain, but the gain is small. Causes of chest pain other than high esophageal pressures and acid reflux must still be sought in most patients with chest pain of unknown origin after a negative cardiac work-up.

  10. Esophageal Cancer in Golestan Province, Iran: A Review of Genetic Susceptibility and Environmental Risk Factors

    PubMed Central

    Gholipour, Mahin; Islami, Farhad; Roshandel, Gholamreza; Khoshnia, Masoud; Badakhshan, Abbas; Moradi, Abdolvahab; Malekzadeh, Reza

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor that is typically diagnosed only when the tumor has gained remarkable size, extended to peripheral tissues, and led to dysphagia. Five-year survival of advanced cancer is still very poor (19%), even with improved surgical techniques and adjuvant chemoradiation therapy. Therefore, early detection and prevention are the most important strategies to reduce the burden of ESCC. Our review will focus on the studies conducted in Golestan province, an area with a high prevalence of ESCC in northern Iran. We review three aspects of the research literature on ESCC: epidemiological features, environmental factors (including substance abuse, environmental contaminants, dietary factors, and human papillomavirus [HPV]), and molecular factors (including oncogenes, tumor suppressor genes, cell cycle regulatory proteins, and other relevant biomarkers). Epidemiological and experimental data suggest that some chemicals and lifestyle factors, including polycyclic aromatic hydrocarbons (PAHs), cigarette smoking, opium use, and hot tea drinking are associated with the development of ESCC in Golestan. HPV infects the esophageal epithelium, but so far, no firm evidence of its involvement in esophageal carcinogenesis has been provided. Some of these factors, notably hot tea drinking, may render the esophageal mucosa more susceptible to injury by other carcinogens. There are few studies at molecular level on ESCC in Golestan. Increasing awareness about the known risk factors of ESCC could potentially reduce the burden of ESCC in the region. Further studies on risk factors, identifying high risk populations, and early detection are needed. PMID:27957288

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

    PubMed Central

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

    2016-01-01

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

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

    ClinicalTrials.gov

    2016-07-30

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

  13. Cellular and molecular immunological mechanisms in eosinophilic esophagitis: an updated overview of their clinical implications.

    PubMed

    Lucendo, Alfredo J

    2014-08-01

    Eosinophilic esophagitis (EoE) is a pathophysiologically complex disorder driven by distinct, multiple mechanisms involving a large number of cells, molecules, and genes. Associated with food allergy from its initial descriptions, a key role for the Th2-type cytokines IL-5 and IL-13 in recruiting and activating eosinophils has been described. Epithelial cells have been recognized as major effectors in initiating EoE, both through their recruitment of iNKT cells towards the esophageal epithelium, which constitutes a major cytokine source, and through the release of eotaxin-3 and other chemoattractants. Epithelial and mesenchymal-released TSLP is a key regulator for which a connecting role between the adaptive and innate mucosal-associated immune response has been suggested. Finally, activated eosinophil- and mast cell-derived TGF β1 secretion is crucial in EoE-associated tissue remodeling.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-12-21

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

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

    ClinicalTrials.gov

    2015-12-10

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

  17. Esophageal Cancer Risk Prediction Models

    Cancer.gov

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

  18. [Esophageal histoplasmosis. A case report].

    PubMed

    Henry, M A; Mendes, E F; Saad, L H; Rodrigues, P A; Gonçalves, I

    1996-01-01

    The authors report a case of a patient with complaint of progressive disphagia. Stenoses of lower third of esophagus was revealed by radiological and endoscopic examinations. Fungi were showed in biopsy of lesion, with demonstration of Histoplasm capsulate by tissue culture. Endoscopic dilatation was performed because especific medical treatment failed but esophageal rupture was observed. Partial esophagectomy was performed with symptoms remission.

  19. Esophageal Carcinoma Following Bariatric Procedures

    PubMed Central

    Leeman, Matthew F.; Richardson, J. David

    2004-01-01

    Background: The long-term success of bariatric operations for weight reduction has been well documented, but their potential effects on the risk of esophageal cancer have not been evaluated. Methods: We performed operations on 3 patients for esophageal cancer following bariatric operations: 2 had Roux-en-Y gastric bypass, and 1 underwent vertical banded gastroplasty. All of these patients had adenocarcinoma at the gastroesophageal junction; 1 involved the entire intrathoracic esophagus. Results: The intervals between the weight-loss operations and cancer diagnoses were 21, 16, and 14 years. All 3 patients had symptoms of reflux for many years before dysphagia developed and cancer was diagnosed. We performed a limited esophagogastrectomy, a classic IvorLewis procedure, and a total esophagectomy with jejunal free-tissue transfer from stomach to cervical esophagus. Two patients had positive lymph nodes. One patient is alive at 6 years; 2 died at 13 and 15 months after undergoing operation for recurrent cancer. Conclusion: The effect of bariatric operations on gastroesophageal reflux is not known, although gastric bypass has been advocated as the “ultimate antireflux procedure.” The presence of esophageal cancer in these 3 patients years after the weight loss operation is worrisome. We believe that patients who develop new symptoms should have endoscopic evaluation and that epidemiologic studies on the incidence of esophageal cancer occurring years after bariatric operation should be performed. PMID:15554284

  20. Responses of the Rat Olfactory Epithelium to Retronasal Air Flow

    PubMed Central

    Scott, John W.; Acevedo, Humberto P.; Sherrill, Lisa; Phan, Maggie

    2008-01-01

    Responses of the rat olfactory epithelium were assessed with the electroolfactogram while odorants were presented to the external nares with an artificial sniff or to the internal nares by positive pressure. A series of seven odorants that varied from very polar, hydrophilic odorants to very non-polar, hydrophobic odorants were used. While the polar odorants activated the dorsal olfactory epithelium when presented by the external nares (orthonasal presentation), they were not effective when forced through the nasal cavity from the internal nares (retronasal presentation). However, the non-polar odorants were effective in both stimulus modes. These results were independent of stimulus concentration or of humidity of the carrier air. Similar results were obtained with multiunit recording from olfactory bulb. These results help to explain why human investigations often report differences in the sensation or ability to discriminate odorants presented orthonasally vs. retronasally. The results also strongly support the importance of odorant sorption in normal olfactory processes. PMID:17215498

  1. Esophageal cancer detection based on tissue surface-enhanced Raman spectroscopy and multivariate analysis

    NASA Astrophysics Data System (ADS)

    Feng, Shangyuan; Lin, Juqiang; Huang, Zufang; Chen, Guannan; Chen, Weisheng; Wang, Yue; Chen, Rong; Zeng, Haishan

    2013-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  3. [Morpho-functional characteristic of oral mucosal epithelium after treatment with a cytostatic drug].

    PubMed

    Leont'eva, I V; Bykov, V L

    2011-01-01

    The effect of cytostatic drug cyclophosphamide (CY) on lingual epithelium was studied in 90 female mice using histological, morphometric, quantitative histochemical and immunohistochemical methods. CY (400 mg/kg) was injected intraperitoneally three times with a 48 h interval. Material was obtained 2 days after injections and 10-20 days after their discontinuation. CY treatment was shown to result in the damage of both surface epithelium of the tongue and the epithelium of minor lingual salivary glands. Damage to the surface epithelium was more pronounced on the ventral surface of the tongue and was associated mainly with the disturbances of its proliferation. Changes were less severe on the dorsal surface and were seen as the disturbances of epithelial differentiation and desquamation. Glandular epithelium was damaged to a lesser extent than the surface one, with serocytes being more sensitive to the cytotoxic injury than mucocytes. After cytostatic drug discontinuation, the tendency for the normalization of the epithelial characteristics was noted. Most persistent changes in the surface epithelium were found on the dorsal surface of the tongue and in the glandular epithelium--in the serous secretory portions of the salivary glands.

  4. The significance of small intestinal epithelium in gastric antral biopsies in children.

    PubMed

    Weinberg, Arthur G

    2012-01-01

    Intestinal metaplasia of the gastric antrum is common in adults with chronic gastritis and occurs in Helicobacter -associated gastritis in children. This study examined the frequency and clinical correlates of intestinal epithelium in 1690 consecutive antral biopsies obtained from children over a 2-year period in a tertiary pediatric care facility. Intestinal epithelium in gastric glands not associated with overlying villi was present in 22 (1.3%) biopsies. These came from 20 patients, 2-17 years of age, none of whom had clinical or histologic evidence of Helicobacter infection or significant chronic gastritis. Eight (40%) had an antral pancreatic rest, 8 had some other localized antral abnormality, and 4 were endoscopically normal. Four additional patients with a pancreatic rest had no intestinal epithelium. Six surgically resected rests and 2 rests found at autopsy were also reviewed. Heterotopic intestinal epithelium was present in 1 of the 2 postmortem specimens but was absent from all 6 surgically resected lesions. No intestinal epithelium was present in 67 antral biopsies with Helicobacter gastritis observed during this same period. Although the intestinal epithelium in these patients could be metaplastic, it more likely represents inadvertent sampling of the gastroduodenal junction induced by a lesion in the distal antrum or a focus of heterotopic epithelium and might best be addressed in the surgical pathology report by a comment to this effect. The distinction from metaplasia is more than semantic, because a diagnosis of intestinal metaplasia can have adverse clinical implications and should be made with caution in a child.

  5. Ineffective Esophageal Motility Progressing into Distal Esophageal Spasm and Then Type III Achalasia

    PubMed Central

    Carlson, Dustin A.; Kahrilas, Peter J.; Pandolfino, John E.

    2016-01-01

    The clinical significance of minor esophageal motility disorders is unclear, though they typically carry a benign course. Distal esophageal spasm progressing to achalasia has been reported, although it appears to be rare. We report a case of a patient with dysphagia and chest pain who was found to have ineffective esophageal motility on high-resolution manometry, which developed into distal esophageal spasm and then progressed to type III achalasia. PMID:28119934

  6. Ineffective Esophageal Motility Progressing into Distal Esophageal Spasm and Then Type III Achalasia.

    PubMed

    Samo, Salih; Carlson, Dustin A; Kahrilas, Peter J; Pandolfino, John E

    2016-08-01

    The clinical significance of minor esophageal motility disorders is unclear, though they typically carry a benign course. Distal esophageal spasm progressing to achalasia has been reported, although it appears to be rare. We report a case of a patient with dysphagia and chest pain who was found to have ineffective esophageal motility on high-resolution manometry, which developed into distal esophageal spasm and then progressed to type III achalasia.

  7. Effect of Monotherapy and Combination Therapy of Pantoprazole and Aprepitant in Gastric Esophageal Reflux Disease in Albino Rats

    PubMed Central

    Shukla, Kamleshwar; Raj, Prince; Kumar, Arun; Kumar, Mukesh; Kaithwas, Gaurav

    2014-01-01

    The present study was undertaken to elucidate the effect of pantoprazole and aprepitant on experimental esophagitis in albino rats. Groups of rats, fasted overnight, received normal saline (3 mL/kg, sham control) or toxic control (3 mL/kg) or pantoprazole (30 mg/kg) or aprepitant (10 mg/kg), or their combinations and were subjected to pylorus and forestomach ligation. Animals were sacrificed after 8 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 pantoprazole and aprepitant significantly inhibited the gastric secretion, total acidity, and esophagitis index. The treatment also helped to restore the altered levels oxidative stress parameters to normal. PMID:24790551

  8. Effect of monotherapy and combination therapy of pantoprazole and aprepitant in gastric esophageal reflux disease in albino rats.

    PubMed

    Shukla, Kamleshwar; Raj, Prince; Kumar, Arun; Kumar, Mukesh; Kaithwas, Gaurav

    2014-01-01

    The present study was undertaken to elucidate the effect of pantoprazole and aprepitant on experimental esophagitis in albino rats. Groups of rats, fasted overnight, received normal saline (3 mL/kg, sham control) or toxic control (3 mL/kg) or pantoprazole (30 mg/kg) or aprepitant (10 mg/kg), or their combinations and were subjected to pylorus and forestomach ligation. Animals were sacrificed after 8 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 pantoprazole and aprepitant significantly inhibited the gastric secretion, total acidity, and esophagitis index. The treatment also helped to restore the altered levels oxidative stress parameters to normal.

  9. Thoracic osteophyte: rare cause of esophageal perforation.

    PubMed

    Rathinam, S; Makarawo, T; Norton, R; Collins, F J

    2010-01-01

    Esophageal perforation is a difficult problem in thoracic surgery. Esophageal perforations can be spontaneous, iatrogenic, or malignant. We report two cases of esophageal perforations caused by thoracic osteophytes and different management strategies leading to successful outcomes. An 80-year-old male presented with chest pain and dysphagia following a fall. On endoscopy, an esophageal perforation and foreign body was noted which was confirmed as a thoracic osteophyte on computed tomography scan. He was managed conservatively as he declined surgery. A 63-year-old male was admitted with dysphagia following a food bolus obstruction. Following esophagoscopy and dilatation, there was clinical and radiological evidence of perforation. During surgery, a thoracic osteophyte was identified as the cause of perforation. The perforation was closed in layers and the osteophyte was trimmed. Both patients recovered well. Thoracic osteophytes are a rare cause of esophageal perforations and a high index of suspicion is required in patients with osteoarthritis who present with esophageal perforations.

  10. Unusual Cause of Esophageal Obstruction in a Neonate Presenting as Esophageal Atresia

    PubMed Central

    Joshi, Shirin S; Dhaded, Sangappa M

    2013-01-01

    Esophageal atresia is the commonest cause of obstruction to esophageal lumen in neonates. Foreign bodies in newborns are extremely rare. We report a rare case of esophageal obstruction closely mimicking atresia due to foreign bodies inserted in a female neonate with homicidal intension. PMID:26023467

  11. Biochemical studies of the tracheobronchial epithelium

    SciTech Connect

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

    1984-06-01

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

  12. STUDIES ON SMALL INTESTINAL CRYPT EPITHELIUM

    PubMed Central

    Trier, Jerry S.

    1963-01-01

    Small intestinal crypt epithelium obtained from normal fasting humans by peroral biopsy of the mucosa was studied with the electron microscope. Paneth cells were identified at the base of the crypts by their elaborate highly organized endoplasmic reticulum, large secretory granules, and small lysosome-like dense bodies within the cytoplasm. Undifferentiated cells were characterized by smaller cytoplasmic membrane-bounded granules which were presumed to be secretory in nature, a less elaborate endoplasmic reticulum, many unattached ribosomes and, in some cells, the presence of glycogen. Some undifferentiated cells at the base of the crypts contained lobulated nuclei and striking paranuclear accumulations of mitochondria. Membrane-bounded cytoplasmic fragments, probably originating from undifferentiated and Paneth cells, were frequently apparent within crypt lumina. Of the goblet cells, some were seen actively secreting mucus. In these, apical mucus appeared to exude into the crypt lumen between gaps in the microvilli. The membrane formerly surrounding the apical mucus appeared to fuse with and become part of the plasma membrane of the cell, suggesting a merocrine secretory mechanism. Enterochromaffin cells were identified by their location between the basal regions of other crypt cells and by their unique intracytoplasmic granules. PMID:14064112

  13. The Kagoshima consensus on esophageal achalasia.

    PubMed

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

    2012-05-01

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

  14. Acute Necrotizing Esophagitis Followed by Duodenal Necrosis.

    PubMed

    Del Hierro, Piedad Magdalena

    2011-12-01

    Acute Necrotizing Esophagitis is an uncommon pathology, characterized by endoscopic finding of diffuse black coloration in esophageal mucosa and histological presence of necrosis in patients with upper gastrointestinal bleeding. The first case of acute necrotizing esophagitis followed by duodenal necrosis, in 81 years old woman with a positive history of Type 2 Diabetes Mellitus, Hypertension, and usual intake of Nonsteroidal Anti-inflammatory drugs, is reported. Although its etiology remains unknown, the duodenal necrosis suggests that ischemia could be the main cause given that the branches off the celiac axis provide common blood supply to the distal esophageal and duodenal tissue. The massive gastroesophagic reflux and NSAID intake could be involved.

  15. Esophageal motility abnormalities in gastroesophageal reflux disease.

    PubMed

    Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

    2014-05-06

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.

  16. Laboratory animal models for esophageal cancer

    PubMed Central

    Nair, Dhanya Venugopalan; Reddy, A. Gopala

    2016-01-01

    The incidence of esophageal cancer is rapidly increasing especially in developing countries. The major risk factors include unhealthy lifestyle practices such as alcohol consumption, smoking, and chewing tobacco to name a few. Diagnosis at an advanced stage and poor prognosis make esophageal cancer one of the most lethal diseases. These factors have urged further research in understanding the pathophysiology of the disease. Animal models not only aid in understanding the molecular pathogenesis of esophageal cancer but also help in developing therapeutic interventions for the disease. This review throws light on the various recent laboratory animal models for esophageal cancer. PMID:27956773

  17. Esophageal sensation and esophageal hypersensitivity - overview from bench to bedside.

    PubMed

    Miwa, Hiroto; Kondo, Takashi; Oshima, Tadayuki; Fukui, Hirokazu; Tomita, Toshihiko; Watari, Jiro

    2010-10-01

    Noxious stimuli in the esophagus activate nociceptive receptors on esophageal mucosa, such as transient receptor potential, acid-sensing ion channel and the P2X family, a family of ligand-gated ion channels responsive to ATP, and this generates signals that are transmitted to the central nervous system via either spinal nerves or vagal nerves, resulting in esophageal sensation. Among the noxious stimuli, gastric acid and other gastric contents are clinically most important, causing typical reflux symptoms such as heartburn and regurgitation. A conventional acid penetration theory has been used to explain the mechanism of heartburn, but much recent evidence does not support this theory. Therefore, it may be necessary to approach the causes of heartburn symptoms from a new conceptual framework. Hypersensitivity of the esophagus, like that of other visceral organs, includes peripheral, central and probably psychosocial factor-mediated hypersensitivity, and is known to play crucial roles in the pathoegenesis of nonerosive reflux disease, functional heartburn and non-cardiac chest pain. There also are esophagitis patients who do not perceive typical symptoms. This condition is known as silent gastroesophageal reflux disease. Although the pathogenesis of silent gastroesophageal reflux disease is still not known, hyposensitivity to reflux of acid may possibly explain the condition.

  18. Eosinophilic esophagitis: an immune-mediated esophageal disease.

    PubMed

    Weinbrand-Goichberg, Jenny; Segal, Idit; Ovadia, Adi; Levine, Arie; Dalal, Ilan

    2013-07-01

    Eosinophilic esophagitis (EoE) is an emerging disease defined by esophageal dysfunction, by typical endoscopic findings and by abnormal eosinophilic inflammation within the esophagus. Eosinophilic accumulation in the esophagus occurs as a result of esophageal overexpression of pro-inflammatory mediators, including T cells and mast cells, cytokines such as interleukin (IL)-13, IL-5 and IL-15, as well as chemoattractants (eotaxin and transforming growth factor-β1, fibroblast growth factor and the newly characterized gene--thymic stromal lymphopoietin, which is a key regulator of allergic sensitization initiation). The role of allergy, particularly food allergy in EoE is indisputable, as elimination diet is a proven commonly used treatment for the disease. However, unlike classical immediate IgE-mediated reaction to allergen, EoE is associated with an altered immune response, characterized by a combination of IgE-mediated and non-IgE-mediated mechanisms. In this review, we aim to discuss the many typical aspects of EoE as opposed to other entities involving the esophagus, with focusing on the aberrant immune-mediated key players contributing to the pathogenesis of this unique disease.

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

    SciTech Connect

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

    2012-04-01

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

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

    PubMed

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

    2007-05-01

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

  1. The pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease.

    PubMed

    Cohen, S; Fisher, R; Lipshutz, W; Turner, R; Myers, A; Schumacher, R

    1972-10-01

    To determine the pathogenesis of esophageal dysfunction in scleroderma and Raynaud's disease, the lower esophageal sphincter (LES) was tested with: (a) methacholine acting directly at the cholinergic receptor on the muscle; (b) edrophonium, a cholinesterase inhibitor, enhancing the effect of released acetylcholine; and (c) gastrin I, acting through the release of acetylcholine. 10 patients with Raynaud's disease and 22 patients with scleroderma were compared with 20 normals and 20 patients with isolated LES incompetence. The mean basal LES pressure in normals was significantly greater than that recorded in both patients with scleroderma and Raynaud's disease. Six patients having scleroderma with normal peristalsis had an LES pressure significantly greater than that noted in 16 patients having scleroderma with abnormal peristalsis. In all groups, the per cent increase in LES pressure was similar when tested by direct muscle stimulation by methacholine. The response to agents that acted indirectly through intact cholinergic nerves differed in these groups. The LES response to gastrin I distinguished patients with normal peristalsis from those with abnormal peristalsis. The patients with normal peristalsis, either with scleroderma or with Raynaud's disease showed only a partial reduction in their response to gastrin I. The response to gastrin I was markedly reduced only in patients with abnormal peristalsis. These data indicate that in patients with scleroderma and Raynaud's disease, the LES response to direct muscle stimulation by methacholine was intact while the response to gastrin I and edrophonium was diminished.

  2. Pradaxa-induced esophageal ulcer.

    PubMed

    Wood, Michele; Shaw, Paul

    2015-10-09

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

  3. Activin Potentiates Proliferation in Mature Avian Auditory Sensory Epithelium

    PubMed Central

    McCullar, Jennifer S.; Ty, Sidya; Campbell, Sean; Oesterle, Elizabeth C.

    2010-01-01

    Humans and other mammals are highly susceptible to permanent hearing and balance deficits due to an inability to regenerate sensory hair cells lost to inner ear trauma. In contrast, nonmammalian vertebrates, such as birds, robustly regenerate replacement hair cells and restore hearing and balance functions to near-normal levels. There is considerable interest in understanding the cellular mechanisms responsible for this difference in regenerative capacity. Here we report on involvement of the TGFβ superfamily type II activin receptors, Acvr2a and Acvr2b, in regulating proliferation in mature avian auditory sensory epithelium. Cultured, posthatch avian auditory sensory epithelium treated with Acvr2a and Acvr2b inhibitors shows decreased proliferation of support cells, the cell type that gives rise to new hair cells. Conversely, addition of activin A, an Acvr2a/b ligand, potentiates support cell proliferation. Neither treatment (inhibitor or ligand) affected hair cell survival, suggesting a specific effect of Acvr2a/b signaling on support cell mitogenicity. Using immunocytochemistry, Acvr2a, Acvr2b, and downstream Smad effector proteins were differentially localized in avian and mammalian auditory sensory epithelia. Collectively, these data suggest that signaling through Acvr2a/b promotes support cell proliferation in mature avian auditory sensory epithelium and that this signaling pathway may be incomplete, or actively blocked, in the adult mammalian ear. PMID:20071511

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

    PubMed Central

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

    2015-01-01

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

  5. Optimal lymphadenectomy for esophageal adenocarcinoma.

    PubMed

    Oezcelik, A

    2013-08-01

    Recently published data have shown that an extended lymphadenectomy during the en bloc esophagectomy leads to a significant increased long-term survival for esophageal adenocarcinoma. On the other hand some studies indicate that the increased survival is based on stage migration and that the surgical complication rate is increased after extended lymphadenectomy. The aim of this review was to give an overview about all aspects of an extended lymphadenectomy in patients with esophageal adenocarcinoma. The review of the literature shows clearly that the number of involved lymph nodes is an independent prognostic factor in patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy leads to an increased long-term survival. Some studies describe that 23 lymph nodes should be removed to predict survival; other studies 18 lymph nodes or 15 lymph nodes. Opponents indicate that the survival benefit is based on stage migration. The studies with a large study population have performed a Cox regression analyzes and identified the number of lymph nodes removed as an independent factor for improved survival, which means it is significant independently from other parameters. Under these circumstances is stage migration not an option to explain the survival benefit. An important difficulty is, that there is no standardized definition of an extended lymphadenectomy, which means the localization and number of removed lymph nodes differ depending from the performing centre. The controversies regarding the survival benefit of the lymphadenectomy is based on the lack of standardisation of the lymphadenectomy. The main goal of further studies should be to generate a clear definition of an extended lymphadenectomy in patients with esophageal adenocarcinoma.

  6. The management of eosinophilic esophagitis.

    PubMed

    Greenhawt, Matthew; Aceves, Seema S; Spergel, Jonathan M; Rothenberg, Marc E

    2013-01-01

    Eosinophilic esophagitis (EoE) is a clinicopathologic, chronic esophageal inflammatory disease resistant to acid suppressive therapy and is associated with variable symptoms indicative of upper gastrointestinal dysfunction. Per current guidelines established by The International Group of Eosinophil Researchers (TIGERS), the diagnosis is made in symptomatic patients after a biopsy that confirms a peak eosinophil level of ≥15 eosinophils/high-powered field (HPF). The esophagus is distinguished by pronounced tissue eosinophilia in which dietary antigens are key inciting factors for disease pathogenesis; EoE being reversed by elimination of triggering food allergens suggests that the disease is mediated in part by allergic sensitization to foods. Moreover, experimental EoE in mice can be induced not only via food exposure but also via aeroallergen exposure. Consistent with an allergic etiology rather than an acid-induced esophagitis, swallowed glucocorticoids are effective for the treatment of EoE. Evaluation by an allergist is a recommended part of the diagnostic workup, especially for management of allergic comorbidities. Clinical practice for the evaluation of patients with EoE mainly relies on prick skin tests due to the ease and validation of these tests in the context of immediate hypersensitivity. However, both atopy patch testing and serum IgE testing have been used in EoE. Herein, we reviewed the basic clinical features of EoE with a focus on the approach to diagnosing causative food allergens and to dietary therapy.

  7. Current knowledge on esophageal atresia

    PubMed Central

    Pinheiro, Paulo Fernando Martins; Simões e Silva, Ana Cristina; Pereira, Regina Maria

    2012-01-01

    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. PMID:22851858

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

    PubMed

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

    2014-05-02

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

  9. A Systematic Review of the Risk of Perforation During Esophageal Dilation for Patients with Eosinophilic Esophagitis

    PubMed Central

    Jacobs, John William

    2011-01-01

    Background Eosinophilic esophagitis (EoE) is associated with tissue remodeling that can result in esophageal mucosal fragility, and esophageal dilation for patients with EoE is known to cause painful mucosal lacerations. Clinicians have been admonished that patients with EoE may be exceptionally predisposed to perforation with esophageal dilation, a notion supported primarily by case reports. We have conducted a systematic review of literature on esophageal dilation in EoE in an attempt to better define the risk of perforation. Methods We searched PubMed and abstracts presented at the annual scientific meetings of the American Gastroenterological Association and the American College of Gastroenterology to identify reports on esophageal dilation in EoE. We analyzed reports meeting the following criteria: (1) the diagnosis was established from esophageal biopsy specimens revealing ≥15 eosinophils/hpf, (2) esophageal dilation was described, (3) esophageal perforations described were the result of esophageal dilation. Results We identified 18 reports for inclusion in our systematic review. The studies comprised 468 patients who underwent a total of 671 endoscopic dilations. Esophageal mucosal tears were described in most cases, but there was only one perforation among the 671 dilations (0.1%). Conclusions Our systematic review does not reveal an inordinate frequency of esophageal perforation from dilation in patients with EoE, and it is not clear that dilation is any more hazardous for patients with EoE than for patients with other causes of esophageal stricture. Although esophageal dilation must be performed with caution in all patients, the risk of perforation in EoE appears to have been exaggerated. PMID:20238250

  10. Clinical effects of eosinophilic esophagitis observed using endoscopic ultrasound.

    PubMed

    Yamabe, Akane; Irisawa, Atsushi; Shibukawa, Goro; Abe, Yoko; Saito, Akiko; Imbe, Koh; Hoshi, Koki; Igarashi, Ryo

    2014-08-01

    A 50-year-old woman was referred to our hospital for dysphagia and several episodes of esophageal food impaction during the prior three months. Complete blood count and basic biochemical tests were normal. No eosinophilia was found. Esophagogastroduodenoscopy (EGD) revealed the presence of concentric rings (esophageal "trachealization") and stenosis along the middle and distal esophagus. Endoscopic ultrasound (EUS) showed circumferential thickening of all layers in the same part. Cytopathologic evaluation of a specimen obtained by endoscopic biopsy of the thickened area in the distal esophagus showed eosinophilic infiltration (20 eosinophils per high-powered field). She was diagnosed as having eosinophilic esophagitis (EoE). Topical steroid therapy was started. A tendency of dysphagia for relief and improvement of characteristic EGD findings began early, but wall thickening in EUS remained. Past reports of the related literature have described that thickness of submucosa and muscularis propria remained after therapy, although significant reduction in the mucosal thickness was provided by short-term steroid therapy. One explanation for early relapse is insufficient reduction in the submucosa and muscularis propria. Consequently, our patient was given steroids until thickness on EUS improved. EUS is regarded as useful for evaluating the curative effect in patients with EoE.

  11. Comparative cytokeratin distribution patterns in cholesteatoma epithelium.

    PubMed

    Olszewska, E; Sudhoff, H

    2007-01-01

    Cytokeratins (CKs) are known as the intermediate filament proteins of epithelial origin. Their distribution in human epithelia is different according to the type of epithelium, state of growth and differentiation. We used monoclonal mouse antibodies against cytokeratins to study CK expression in the following human tissues: cholesteatoma, middle ear mucosa, glandular epithelium, and meatal ear canal epithelium. Immunohistochemical processing was performed using the labeled steptavidin peroxidase method to demonstrate the presence of CKs in cells of human epidermis. Positive reaction was obtained for CK4, CK34betaE12, CK10, CK14 in skin and cholesteatoma epithelium. However, a more extensive positive reaction with those CKs was observed in cholesteatoma epithelium. Positive immunoreactivity was seen with anti- CK19 in the glandular epithelium. Middle ear mucosa specimens revealed positive immunoreactivity with the antibodies against CK4. The expression of CK4 was definitely positive within the basal layers of the epidermis. The glandular epithelium showed no positive reaction with anti- CK4, anti- CK34betaE12, anti- CK14 and anti-CK10. Immunohistochemistry for CK18 showed no reaction in all examined tissues. Cholesteatoma is known as a proliferative disease in the middle ear which pathogenesis is not completely understood. Keratinocytes express hyperproliferation- associated CKs and after reaching the suprabasal layers they finally undergo apoptosis creating keratinous debris. Cytokeratin expression observed in the epithelium explains proliferative behavior of cholesteatoma which is associated with increased keratinocyte migration. Cytokeratins can be used as potential proliferative markers. It can also allow for searching the usefulness of inhibiting regulators in the treatment of hyperproliferative diseases.

  12. Erlotinib Hydrochloride in Treating Patients With Advanced Esophageal Cancer or Stomach Cancer

    ClinicalTrials.gov

    2013-06-03

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Recurrent Esophageal Cancer; Squamous Cell Carcinoma of the Esophagus; Stage III Esophageal Cancer; Stage IV Esophageal Cancer

  13. Eosinophilic esophageal myositis diagnosed by endoscopic ultrasound-guided fine-needle aspiration biopsy: a case report.

    PubMed

    Igarashi, Ryo; Irisawa, Atsushi; Shibukawa, Goro; Yamabe, Akane; Fujisawa, Mariko; Sato, Ai; Maki, Takumi; Arakawa, Noriyuki; Yoshida, Yoshitsugu; Yamamoto, Shogo; Ikeda, Tsunehiko

    2016-10-01

    Eosinophilic esophagitis (EoE) is diagnosed by microscopic findings of eosinophilic infiltration into the squamous epithelium. In contrast, another disease concept termed "eosinophilic esophageal myositis (EoEM)" has been proposed, whereby there is eosinophilic infiltration into the muscularis propria instead. A 60-year-old man was referred to our hospital for chest pain, dysphagia, and several episodes of esophageal food impaction. Although EoE was suspected based on clinical features, biopsy specimens showed no mucosal eosinophilic infiltration. Endoscopic ultrasound (EUS) showed thickening of the muscularis propria layer and subsequent EUS-guided fine-needle aspiration biopsy (EUS-FNA) revealed eosinophilic infiltration into the muscularis propria. Although the patient's symptoms gradually improved after steroid administration, complete remission was not achieved after 1 year of treatment. This case may reflect a disorder distinct from typical EoE based on eosinophilic infiltration of the muscularis propria but not the squamous epithelium, and we, therefore, diagnosed it as EoEM using the EUS-FNA findings as reference.

  14. Esophageal diverticula in Parma wallabies (Macropus parma).

    PubMed

    Okeson, Danelle M; Esterline, Meredith L; Coke, Rob L

    2009-03-01

    Four adult, wild caught Parma wallabies (Macropus parma) presented with intermittent, postprandial, midcervical swellings. Esophageal diverticula were discovered in the four animals. One of two wallabies was managed successfully with surgery. A third animal died of other causes. The fourth animal died with possible complications from the diverticulum. This is the first published report of esophageal diverticula in macropods.

  15. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  16. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  17. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  18. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  19. 21 CFR 878.3610 - Esophageal prosthesis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  20. Comparative genomic analysis of esophageal cancers.

    PubMed

    Caygill, Christine P J; Gatenby, Piers A C; Herceg, Zdenko; Lima, Sheila C S; Pinto, Luis F R; Watson, Anthony; Wu, Ming-Shiang

    2014-09-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on comparative genomic analysis of esophageal cancers: genomic polymorphisms, the genetic and epigenetic drivers in esophageal cancers, and the collection of data in the UK Barrett's Oesophagus Registry.

  1. Osmotic regulation of airway reactivity by epithelium.

    PubMed

    Fedan, J S; Yuan, L X; Chang, V C; Viola, J O; Cutler, D; Pettit, L L

    1999-05-01

    Inhalation of nonisotonic solutions can elicit pulmonary obstruction in asthmatic airways. We evaluated the hypothesis that the respiratory epithelium is involved in responses of the airways to nonisotonic solutions using the guinea pig isolated, perfused trachea preparation to restrict applied agents to the mucosal (intraluminal) or serosal (extraluminal) surface of the airway. In methacholine-contracted tracheae, intraluminally applied NaCl or KCl equipotently caused relaxation that was unaffected by the cyclo-oxygenase inhibitor, indomethacin, but was attenuated by removal of the epithelium and Na+ and Cl- channel blockers. Na+-K+-2Cl- cotransporter and nitric oxide synthase blockers caused a slight inhibition of relaxation, whereas Na+,K+-pump inhibition produced a small potentiation. Intraluminal hyperosmolar KCl and NaCl inhibited contractions in response to intra- or extraluminally applied methacholine, as well as neurogenic cholinergic contractions elicited with electric field stimulation (+/- indomethacin). Extraluminally applied NaCl and KCl elicited epithelium-dependent relaxation (which for KCl was followed by contraction). In contrast to the effects of hyperosmolarity, intraluminal hypo-osmolarity caused papaverine-inhibitable contractions (+/- epithelium). These findings suggest that the epithelium is an osmotic sensor which, through the release of epithelium-derived relaxing factor, can regulate airway diameter by modulating smooth muscle responsiveness and excitatory neurotransmission.

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

    SciTech Connect

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

    2015-09-11

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

  3. The hypertensive lower esophageal sphincter: a motility disorder with manometric features of outflow obstruction.

    PubMed

    Gockel, Ines; Lord, Reginald V N; Bremner, Cedric G; Crookes, Peter F; Hamrah, Pedram; DeMeester, Tom R

    2003-01-01

    The aim of this study was to define the clinical presentation, motility characteristics, and prevalence and patterns of gastroesophageal reflux in patients with hypertensive lower esophageal sphincter (HTLES). HTLES was defined by a resting pressure measured at the respiratory inversion point on stationary manometry of greater than 26 mm Hg (ninety-fifth percentile of normal). One hundred consecutive patients (80 women, 20 men; mean age 54.7 years, range 23 to 89 years), diagnosed with HTLES at our institution between September 1996 and October 1999, were studied. Patients with achalasia or other named esophageal motility disorders or history of foregut surgery were excluded, but patients with both HTLES and "nutcracker esophagus" were included. The most common symptoms in patients with HTLES were regurgitation (75%), heartburn (71%), dysphagia (71%), and chest pain (49%). The most common primary presenting symptoms were heartburn and dysphagia. The intrabolus pressure, which is a manometric measure of outflow obstruction, was significantly higher in patients with HTLES compared to normal volunteers. The residual pressure measured during LES relaxation induced by a water swallow was also significantly higher than in normal persons. There were no significant associations between any of the relaxation parameters studied (residual pressure, nadir pressure, duration of relaxation, time to residual pressure) and either the presence or severity of any symptoms or the presence of abnormal esophageal acid exposure. Seventy-three patients underwent 24-hour pH monitoring, and 26% had increased distal esophageal acid exposure. Compared to a cohort of patients with gastroesophageal reflux disease but no HTLES (n=300), the total and supine periods of distal esophageal acid exposure were significantly lower in the patients with HTLES and abnormal acid exposure. Patients with HTLES frequently present with moderately severe dysphagia and typical reflux symptoms. Approximately one

  4. Laser-induced fluorescence in the detection of esophageal carcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Kenneth K.; Gutta, Kumar; Laukka, Mark A.; Densmore, John

    1995-01-01

    Laser induced fluorescence (LIF) is a technique which can perform an 'optical biopsy' of gastrointestinal mucosa. LIF was performed in resected specimens using a pulsed N2-laser coupled fiberoptically to a probe. Fluorescence was measured using a 0.2 meter spectroscope with an intensified photodiode array. Measurements were made on fresh (<30 minutes after resection) esophageal specimens containing normal mucosa, Barrett's esophagus, and adenocarcinoma. Each tissue section was examined using an optical probe consisting of a central fiber for delivering the excitation energy and a 6 fiber bundle surrounding the central fiber for detection of the fluorescence. An excitation wavelength of 337 nm was used which generated 3-ns pulses while fluorescence intensities were acquired from 300-800 nm. Spectra were obtained from each section in a standardized fashion and background spectra subtracted. Fluorescence readings were taken from 54 normal esophageal sections and 32 sections of adenocarcinoma. A fluorescence index obtained from the tumor sections was 0.68+/- 0.01 compared with 0.51+/- 0.01 for the normal sections (p<0.001). Using a discriminant value of 0.65, this technique had a sensitivity of 81% and a specificity of 100% for detection of malignant tissue. The positive predictive value was 100% and the negative predictive value was 90% for an overall accuracy of 93%. LIF is a promising technique which has the capability of distinguishing normal versus malignant tissue in the esophagus with good accuracy.

  5. Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

    PubMed Central

    Kuick, Rork; Thomas, Dafydd G.; Nadal, Ernest; Lin, Jules; Chang, Andrew C.; Reddy, Rishindra M.; Orringer, Mark B.; Taylor, Jeremy M. G.; Wang, Thomas D.; Beer, David G.

    2016-01-01

    The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies. PMID:27363029

  6. Multimodal near infrared spectral imaging as an exploratory tool for dysplastic esophageal lesion identification

    NASA Astrophysics Data System (ADS)

    Lieber, Chad A.; Urayama, Shiro; Rahim, Nazir; Tu, Raymond; Saroufeem, Ramez; Reubner, Boris; Demos, Stavros G.

    2006-03-01

    We explore nine different combinations of fluorescence, light scattering, and polarization spectral imaging approaches in the near-infrare spectral region toward the diagnosis of pathologic and normal esophageal lesions. The combinations of all the imaging techniques were evaluated for maximal sensitivity and specificity. The results suggest that this multimodal approach is capable of highly accurate detection of the presence of pathologic tissue.

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

    PubMed Central

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

    2015-01-01

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

  8. Clinical Utility of Esophageal manometry in the patients with dysphagia – Experience from Sudan

    PubMed Central

    Abbas, Amin M; Medani, Sami; Abdallah, Tajeldin M; Gasim, Gasim I

    2016-01-01

    Objectives The aim of this study was to assess the clinical utility of esophageal manometry among Sudanese patients presenting to the National Centre for Gastrointestinal and Liver Diseases, Ibn Sina Hospital, Khartoum, Sudan. Methodology Consecutive patients referred for esophageal manometry at the aforementioned center from July 2008 through January 2011 were included in the study. Manometric studies were done after stopping medicines with a known effect on esophageal motility and an overnight fast. Immediately before the manometric study, the patients’ history and clinical examination were recorded using a structured questionnaire. Results The major referral reason was the investigation of dysphagia in 78 patients (60.5%), followed by the evaluation of Gastroesophageal reflux disease (GERD) in 39 patients (30%), while 11 patients (9%) were referred because of non-cardiac chest pain. The manometric diagnosis in the 78 patients with dysphagia, where 51(65.4%) had achalasia, 13(16.7%) had nonspecific motility disorder, the remaining percentage was formed by GERD diffuse esophageal spasm, connective tissue disease, Nutcracker esophagus, hypertensive lower esophageal sphincter, patient manometry suggestive of myasthenia gravis, and normal manometry. Conclusion GERD and Achalasia were the commonest conditions among the study group. Patients presenting with achalasia manifest the same clinical symptoms as published in the literature. The leading abnormality predisposing to GERD was hypotensive lower esophageal sphincter and weak esophageal clearance function. GERD was main cause of non-cardiac chest pain in the study population. However, it is difficult to generalize the findings of this study for the whole country since it was a single center study. PMID:27833517

  9. Nitrazepam-induced cricopharyngeal dysphagia, abnormal esophageal peristalsis and associated bronchospasm: probable cause of nitrazepam-related sudden death.

    PubMed

    Lim, H C; Nigro, M A; Beierwaltes, P; Tolia, V; Wishnow, R

    1992-09-01

    Nitrazepam was used in the treatment of resistant myoclonic epilepsy in 38 children. After the occurrence of nitrazepam-associated swallowing incoordination, high-peaked esophageal peristalsis and related bronchospasm in one patient, we initiated a prospective study of esophageal manometry using a station pull-through technique with a pediatric 4-channel continuous perfusing system. Three more patients were found to have delayed cricopharyngeal relaxation and high-peaked esophageal peristaltic waves. The initial patient developed severe respiratory distress and bronchospasm necessitating ventilatory support while on nitrazepam and improved dramatically with subsequent normal manometric study following nitrazepam discontinuation. Nitrazepam was reintroduced for its anticonvulsant and cognitive benefits and was tolerated at a reduced dosage. We postulate a central nervous system effect of nitrazepam promoting parasympathetic overactivity or vagotonia which can cause potentially fatal respiratory distress. Care must be exercised in nitrazepam use and esophageal manometry may be helpful in defining patients at greater risk for sudden death.

  10. Lymphocytic Esophagitis in Nonachalasia Primary Esophageal Motility Disorders: Improved Criteria, Prevalence, Strength of Association, and Natural History.

    PubMed

    Putra, Juan; Muller, Kristen E; Hussain, Zilla H; Parker, Siddhartha; Gabbard, Scott; Brickley, Elizabeth B; Lacy, Brian E; Rothstein, Richard; Lisovsky, Mikhail

    2016-12-01

    Lymphocytic esophagitis (LE) is a histologic pattern with no established clinical correlates in the majority of patients. The goal of this study was to evaluate the association between nonachalasia primary esophageal motility disorders (PEMD) and LE. Sixty-nine patients with PEMD and esophageal biopsies, including 22 with nutcracker esophagus, 33 with ineffective motility, and 14 with diffuse spasm, constituted the study group. The control group consisted of 70 patients with severe dysmotility-negative gastroesophageal reflux disease requiring referral for Nissen fundoplication. To improve the criteria for LE, a lymphocyte reference range at different esophageal levels was first established in 17 healthy volunteers. The cutoffs for normal intraepithelial lymphocytes, defined as lymphocyte levels not exceeding mean level±2 SDs, were set at 62, 46, and 41 lymphocytes per high-power field at 0 to 2, 5, and 10 cm above the gastroesophageal junction, respectively. Predominantly focal peripapillary LE was observed in approximately 40% of patients with nutcracker esophagus or diffuse spasm and in 20% of patients with ineffective motility, in comparison with 4% of patients with dysmotility-negative gastroesophageal reflux disease (P<0.035 vs. any subtype of PEMD). Overall, LE was strongly associated with PEMD in multivariate analysis (adjusted odds ratio, 7.93; 95% confidence interval, 2.26-27.9; P=0.001). LE had a chronic course in 56% of the patients with follow-up biopsies. In conclusion, LE has a strong association with PEMD, suggesting the utility of LE in raising the possibility of PEMD.

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

    PubMed

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

    2016-01-26

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

  12. Esophageal mucosal damage may promote dysmotility and worsen esophageal acid exposure.

    PubMed

    Meneghetti, Adam T; Tedesco, Pietro; Damani, Tanuja; Patti, Marco G

    2005-12-01

    This study determines the relationship among esophageal dysmotility, esophageal acid exposure, and esophageal mucosal injury in patients with gastroesophageal reflux disease (GERD). A total of 827 patients with GERD (confirmed by ambulatory pH monitoring) were divided into three groups based on the degree of mucosal injury: group A, no esophagitis, 493 patients; group B, esophagitis grades I to III, 273 patients; and group C, Barrett's esophagus, 61 patients. As mucosal damage progressed from no esophagitis to Barrett's esophagus, there was a significant decrease in lower esophageal sphincter pressure and amplitude of peristalsis in the distal esophagus, with a subsequent increase in the number of reflux episodes in 24 hours, the number of reflux episodes longer than 5 minutes, and the reflux score. These data suggest that in patients with GERD, worsening of esophageal mucosal injury may determine progressive deterioration of esophageal motor function with impairment of acid clearance and increase of esophageal acid exposure. These findings suggest that Barrett's esophagus is an end-stage form of gastroesophageal reflux, and that if surgical therapy is performed early in the course of the disease, this cascade of events might be blocked.

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

    SciTech Connect

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

    2012-01-01

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

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

    PubMed Central

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

    1992-01-01

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

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

    PubMed

    Wei, Lu; Wang, Fei; Chen, Shuyan

    2015-01-01

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

  16. Nd:YAG laser versus polidocanol injection for palliation of esophageal malignancy: a prospective, randomized study.

    PubMed

    Angelini, G; Pasini, A F; Ederle, A; Castagnini, A; Talamini, G; Bulighin, G

    1991-01-01

    Palliation is often the only treatment that can be offered to patients affected by esophageal malignancy. This prospective study was carried out in order to compare two endoscopic palliative treatments: Nd:YAG laser and local injection of 3% polidocanol. We randomized 34 patients with inoperable malignancies to one of the two treatments. After the first course, 88.8% of the patients in the laser group and 81.5% in the polidocanol group were able to swallow a normal oral caloric intake. Only one major complication (esophageal perforation) was observed (polidocanol group) and was successfully treated with endoscopic placement of a prosthesis. We believe that both techniques are safe and effective for the palliation of esophageal malignant strictures but that polidocanol injection is cheap, simple, and more widely available.

  17. Esophageal ulcer caused by cytomegalovirus: resolution during combination antiretroviral therapy for acquired immunodeficiency syndrome.

    PubMed

    Mönkemüller, K E; Wilcox, C M

    2000-08-01

    A 36-year-old man with a 5-year history of untreated human immunodeficiency virus (HIV) infection had odynophagia for 14 days. Fifteen days earlier, he had begun taking trimethoprim-sulphamethoxazole and combination antiretroviral therapy that included lamivudine, zidovudine, and nelfinavir. He had no history of opportunistic infection. The CD4 lymphocyte count was 67/microL and HIV-RNA level was 359,396 copies/mL. Esophagogastroduodenoscopy revealed a large, well-circumscribed esophageal ulceration 31 cm from the incisors. Histopathologic examination of esophageal biopsy specimens showed cytopathic changes diagnostic of cytomegalovirus (CMV). In situ DNA hybridization was positive for CMV. While combination antiretroviral therapy was continued, the esophageal symptoms resolved within 4 days of endoscopy without specific therapy for CMV. Follow-up endoscopy 4 weeks later revealed a normal-appearing esophagus, and the patient has remained symptom-free for 10 months.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. Habitual rapid food intake and ineffective esophageal motility

    PubMed Central

    Li, Kong-Ling; Chen, Ji-Hong; Zhang, Qian; Huizinga, Jan D; Vadakepeedika, Shawn; Zhao, Yu-Rong; Yu, Wen-Zhen; Luo, He-Sheng

    2013-01-01

    AIM: To study non-cardiac chest pain (NCCP) in relation to ineffective esophageal motility (IEM) and rapid food intake. METHODS: NCCP patients with a self-reported habit of fast eating underwent esophageal manometry for the diagnosis of IEM. Telephone interviews identified eating habits of additional IEM patients. Comparison of manometric features was done among IEM patients with and without the habit of rapid food intake and healthy controls. A case study investigated the effect of 6-mo gum chewing on restoration of esophageal motility in an IEM patient. The Valsalva maneuver was performed in IEM patients and healthy controls to assess the compliance of the esophagus in response to abdominal pressure increase. RESULTS: Although most patients diagnosed with NCCP do not exhibit IEM, remarkably, all 12 NCCP patients who were self-reporting fast eaters with a main complaint of chest pain (75.0%) had contraction amplitudes in the mid and distal esophagus that were significantly lower compared with healthy controls [(23.45 mmHg (95%CI: 14.06-32.85) vs 58.80 mmHg (95%CI: 42.56-75.04), P < 0.01 and 28.29 mmHg (95%CI: 21.77-34.81) vs 50.75 mmHg (95%CI: 38.44-63.05), P < 0.01, respectively)]. In 7 normal-eating IEM patients with a main complaint of sensation of obstruction (42.9%), the mid amplitude was smaller than in the controls [30.09 mmHg (95%CI: 19.48-40.70) vs 58.80 mmHg (95%CI: 42.56-75.04), P < 0.05]. There was no statistically significant difference in manometric features between the fast-eating and normal-eating groups. One NCCP patient who self-reported fast eating and was subsequently diagnosed with IEM did not improve with proton-pump inhibition but restored swallow-induced contractions upon 6-mo gum-chewing. The Valsalva maneuver caused a markedly reduced pressure rise in the mid and proximal esophagus in the IEM patients. CONCLUSION: Habitual rapid food intake may lead to IEM. A prospective study is needed to validate this hypothesis. Gum-chewing might

  1. Activity assessment of eosinophilic esophagitis.

    PubMed

    Schoepfer, Alain; Safroneeva, Ekaterina

    2014-01-01

    The activity of eosinophilic esophagitis (EoE) can be assessed with patient-reported outcomes and biologic measures. Patient-reported outcomes include symptoms and quality of life, whereas biologic measures refer to endoscopic, histologic, and biochemical activity (e.g. blood biomarkers). So far, a validated tool to assess EoE activity in the above-mentioned dimensions is lacking. Given the lack of a standardized way to assess EoE activity in the various dimensions, the results of different clinical trials may be difficult to compare. For symptom assessment in adult patients, the symptom 'dysphagia' should be evaluated according to different standardized food consistencies. Furthermore, symptom assessment should take into account the following items: avoidance of specific food categories, food modification, and time to eat a regular meal. A distinct symptom recall period (e.g. 2 weeks) has to be defined for symptom assessment. Performing an 'esophageal stress test' with ingestion of a standardized meal to measure symptom severity bears the potential risk of acute food bolus impaction and should therefore be avoided. The description of endoscopic findings in EoE has meanwhile been standardized. Histologic evaluation of EoE activity should report either the size of the high-power field used or count the eosinophils per mm(2). There is a current lack of blood biomarkers demonstrating a good correlation with histologic activity in esophageal biopsies. The development and validation of an adult and pediatric EoE activity index is urgently needed not only for clinical trials and observational studies, but also for daily practice.

  2. Endoscopic management of esophageal varices.

    PubMed

    Poza Cordon, Joaquin; Froilan Torres, Consuelo; Burgos García, Aurora; Gea Rodriguez, Francisco; Suárez de Parga, Jose Manuel

    2012-07-16

    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.

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

    PubMed Central

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

    2015-01-01

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

  4. RHBDF2 Mutations Are Associated with Tylosis, a Familial Esophageal Cancer Syndrome

    PubMed Central

    Blaydon, Diana C.; Etheridge, Sarah L.; Risk, Janet M.; Hennies, Hans-Christian; Gay, Laura J.; Carroll, Rebecca; Plagnol, Vincent; McRonald, Fiona E.; Stevens, Howard P.; Spurr, Nigel K.; Bishop, D. Timothy; Ellis, Anthony; Jankowski, Janusz; Field, John K.; Leigh, Irene M.; South, Andrew P.; Kelsell, David P.

    2012-01-01

    Tylosis esophageal cancer (TOC) is an autosomal-dominant syndrome characterized by palmoplantar keratoderma, oral precursor lesions, and a high lifetime risk of esophageal cancer. We have previously localized the TOC locus to a small genomic interval within chromosomal region 17q25. Using a targeted capture array and next-generation sequencing, we have now identified missense mutations (c.557T>C [p.Ile186Thr] and c.566C>T [p.Pro189Leu] in RHBDF2, which encodes the inactive rhomboid protease RHBDF2 (also known as iRhom2), as the underlying cause of TOC. We show that the distribution of RHBDF2 in tylotic skin is altered in comparison with that in normal skin, and immortalized tylotic keratinocytes have decreased levels of total epidermal growth factor receptor (EGFR) and display an increased proliferative and migratory potential relative to normal cells, even when normal cells are stimulated with exogenous epidermal growth factor. It would thus appear that EGFR signaling is dysregulated in tylotic cells. Furthermore, we also show an altered localization of RHBDF2 in both tylotic and sporadic squamous esophageal tumors. The elucidation of a role of RHBDF2 in growth-factor signaling in esophageal cancer will help to determine whether targeting this pathway in chemotherapy for this and other squamous cell carcinomas will be effective. PMID:22265016

  5. Olfactory epithelium changes in germfree mice

    PubMed Central

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

    2016-01-01

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

  6. Esophageal and gastric cancers with metastases induced in dogs by N-ethyl-N'-nitro-N-nitrosoguanidine.

    PubMed

    Sasajima, K; Kawachi, T; Sano, T; Sugimura, T; Shimosato, Y

    1977-06-01

    Three 6-month-old male beagle dogs were given a solution of 150 microng N-ethyl-N'-nitrosoguanidine (ENNG)/ml to drink ad libitum for 9 months. They all developed esophageal squamous cell carcinomas and gastric adenocarcinomas. The stomach adenocarcinomas were mostly in the antrum along the lesser curvature and were either well differentiated or poorly differentiated, with or without signet ring cells. The well-differentiated adenocarcinomas metastasized to the liver, and the poorly differentiated ones metastasized to the lymph nodes. The gastric mucosa in the antrum was atrophic, and the muscularis mucosae was fibrotic. Esophageal lesions were multicentric moderately differentiated squamous cell carcinomas, and they developed without diffuse hyperplastic changes of the epithelium. One dog with a large ulcerated carcinoma of the esophagus had metastases in the lung, liver, peritoneum, and abdominal lymph nodes. One dog also had a hemangiosarcoma with hepatic metastasis and spindle cell sarcoma in the stomach and duodenum, respectively.

  7. Esophageal hypersensitivity in noncardiac chest pain.

    PubMed

    Min, Yang Won; Rhee, Poong-Lyul

    2016-09-01

    Noncardiac chest pain (NCCP) is an often-encountered clinical problem. Although many patients suffer from persistent or recurrent chest pain, treatment remains a challenge owing to its various possible etiologies. Gastroesophageal reflux disease (GERD) is the most common cause of NCCP. In GERD-related NCCP, proton pump inhibitor treatment appears to be effective. However, the pathophysiology remains to be fully elucidated in NCCP patients without GERD. Treatment for non-GERD-related NCCP has been aimed at esophageal motility disorders and visceral hypersensitivity. As there is growing evidence that esophageal visceral hypersensitivity plays a role in NCCP, pain modulators have become the mainstay of therapy in patients with non-GERD-related NCCP. However, there is an unmet need for the treatment of esophageal hypersensitivity in NCCP due to modest evidence for the benefit of pain modulators, including antidepressants, in non-GERD-related NCCP. Recent studies have demonstrated that esophageal mast cell infiltration and impaired mucosal integrity are related to visceral hypersensitivity in patients with NCCP. Thus, esophageal mast cell stabilization and restoration of esophageal mucosal integrity could be considered potential therapeutic targets in selected NCCP patients with hypersensitivity. However, further observations are necessary to shed light on esophageal hypersensitivity in NCCP.

  8. Dicer function is essential for lung epithelium morphogenesis.

    PubMed

    Harris, Kelley S; Zhang, Zhen; McManus, Michael T; Harfe, Brian D; Sun, Xin

    2006-02-14

    DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only a single Dicer gene exists in the mouse genome, and it is broadly expressed in developing tissues. Dicer-null mutants die before gastrulation. Therefore, to study Dicer function in the later event of lung formation, we inactivated it in the mouse lung epithelium using a Dicer conditional allele and the Sonic Hedgehogcre (Shhcre) allele. Branching arrests in these mutant lungs, although epithelial growth continues in distal domains that are expanded compared with normal samples. These defects result in a few large epithelial pouches in the mutant lung instead of numerous fine branches present in a normal lung. Significantly, the initial phenotypes are apparent before an increase in epithelial cell death is observed, leading us to propose that Dicer plays a specific role in regulating lung epithelial morphogenesis independent of its requirement in cell survival. In addition, we found that the expression of Fgf10, a key gene involved in lung development, is up-regulated and expanded in the mesenchyme of Dicer mutant lungs. Previous studies support the hypothesis that precise localization of FGF10 in discrete sites of the lung mesenchyme serves as a chemoattractant for the outgrowth of epithelial branches. The aberrant Fgf10 expression may contribute to the Dicer morphological defects. However, the mechanism by which DICER functions in the epithelium to influence Fgf10 expression in the mesenchyme remains unknown.

  9. Microbial flora of the normal esophagus.

    PubMed

    Gagliardi, D; Makihara, S; Corsi, P R; Viana, A de T; Wiczer, M V; Nakakubo, S; Mimica, L M

    1998-10-01

    The endogenous flora of the skin and some mucous membranes are well known, however, we were unable to find descriptions about normal esophageal flora in literature. We believe that knowledge about normal esophageal flora is important for therapeutic implications. We compiled data on 30 patients without infection of the oropharynx or esophagus who were admitted for an endoscopy of the upper digestive tract to determine normal esophageal flora. The samples were collected by injecting 10 ml of 0.9% physiological solution into the esophagus and oropharynx and removing it by suction. Esophageal samples from 30 patients and oropharingeal samples from 10 of these patients were collected. We identified mixed flora being Streptococcus viridans the most frequent microorganism found. Where samples from both the esophagus and oropharynx were collected, three occurrences of this same microorganism were found. We concluded that the isolation frequency of germs in the esophagus by the method used was high and the most frequently found germ was S. viridans. There is therefore a possible correlation between the flora from the oropharynx and the esophagus.

  10. [Quantitative image analysis in pulmonary pathology - digitalization of preneoplastic lesions in human bronchial epithelium (author's transl)].

    PubMed

    Steinbach, T; Müller, K M; Kämper, H

    1979-01-01

    The report concerns the first phase of a quantitative study of normal and abnormal bronchial epithelium with the objective of establishing the digitalization of histologic patterns. Preparative methods, data collecting and handling, and further mathematical analysis are described. In cluster and discriminatory analysis the digitalized histologic features can be used to separate and classify the individual cases into the respective diagnostic groups.

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

    PubMed

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

    2012-06-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. Oxidative stress-induced posttranslational modification of TRPV1 expressed in esophageal epithelial cells.

    PubMed

    Kishimoto, Etsuko; Naito, Yuji; Handa, Osamu; Okada, Hitomi; Mizushima, Katsura; Hirai, Yasuko; Nakabe, Nami; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Yagi, Nobuaki; Kokura, Satoshi; Yoshida, Norimasa; Yoshikawa, Toshikazu

    2011-08-01

    Human esophageal epithelium is continuously exposed to physical stimuli or to gastric acid that sometimes causes inflammation of the mucosa. Transient receptor potential vanilloid 1 (TRPV1) is a nociceptive, Ca(2+)-selective ion channel activated by capsaicin, heat, and protons. It has been reported that activation of TRPV1 expressed in esophageal mucosa is involved in gastroesophageal reflux disease (GERD) or in nonerosive GERD symptoms. In this study, we examined the expression and function of TRPV1 in the human esophageal epithelial cell line Het1A, focusing in particular on the role of oxidative stress. Interleukin-8 (IL-8) secreted by Het1A cells upon stimulation by capsaicin or acid with/without 4-hydroxy-2-nonenal (HNE) was measured by ELISA. Following capsaicin stimulation, the intracellular production of reactive oxygen species (ROS) was determined using a redox-sensitive fluorogenic probe, and ROS- and HNE-modified proteins were determined by Western blotting using biotinylated cysteine and anti-HNE antibody, respectively. HNE modification of TRPV1 proteins was further investigated by immunoprecipitation after treatment with synthetic HNE. Capsaicin and acid induced IL-8 production in Het1A cells, and this production was diminished by antagonists of TRPV1. Capsaicin also significantly increased the production of intracellular ROS and ROS- or HNE-modified proteins in Het1A cells. Moreover, IL-8 production in capsaicin-stimulated Het1A cells was enhanced by synthetic HNE treatment. Immunoprecipitation studies revealed that TRPV1 was modified by HNE in synthetic HNE-stimulated Het1A cells. We concluded that TRPV1 functions in chemokine production in esophageal epithelial cells, and this function may be regulated by ROS via posttranslational modification of TRPV1.

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

    SciTech Connect

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

    2007-10-01

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

  16. Food intolerances and eosinophilic esophagitis in childhood.

    PubMed

    Ozdemir, Oner; Mete, Emin; Catal, Ferhat; Ozol, Duygu

    2009-01-01

    Food intolerance is an adverse reaction to a particular food or ingredient that may or may not be related to the immune system. A deficiency in digestive enzymes can also cause some types of food intolerances like lactose and gluten intolerance. Food intolerances may cause unpleasant symptoms, including nausea, bloating, abdominal pain, and diarrhea, which usually begin about half an hour after eating or drinking the food in question, but sometimes symptoms may delayed up to 48 h. There is also a strong genetic pattern to food intolerances. Intolerance reactions to food chemicals are mostly dose-related, but also some people are more sensitive than others. Diagnosis can include elimination and challenge testing. Food intolerance can be managed simply by avoiding the particular food from entering the diet. Babies or younger children with lactose intolerance can be given soy milk or hypoallergenic milk formula instead of cow's milk. Adults may be able to tolerate small amounts of troublesome foods, so may need to experiment. Eosinophilic esophagitis (EE) is defined as isolated eosinophilic infiltration in patients with reflux-like symptoms and normal pH studies and whose symptoms are refractory to acid-inhibition therapy. Food allergy, abnormal immunologic response, and autoimmune mechanisms are suggested as possible etiological factors for EE. This article is intended to review the current literature and to present a practical approach for managing food intolerances and EE in childhood.

  17. Esophageal irritation due to alendronate sodium tablets: possible mechanisms.

    PubMed

    Peter, C P; Handt, L K; Smith, S M

    1998-09-01

    Animal studies were done using an in vivo dog model to examine the possible mechanism for the esophageal adverse events reported with alendronate sodium tablets. These studies showed that under low pH conditions alendronate sodium can cause esophageal irritation. No esophageal irritation occurred at pH 3.5 or higher where the drug exists primarily as the sodium salt. The animal studies also showed that alendronate sodium can exacerbate preexisting esophageal damage. Exposure of the esophageal mucosa for a prolonged period to alendronate sodium tablet can also cause mild esophageal irritation. These findings suggest that the esophageal irritation in patients taking Fosamax can be from prolonged contact with the tablet, reflux of acidic gastric contents with alendronate sodium, and exacerbation of preexisting esophageal damage. The findings also suggest that other bisphosphonates can cause esophageal injury under similar conditions.

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

    PubMed Central

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

    2015-01-01

    This study investigated the impact of selective epithelial injury on phonation in an excised human larynx apparatus. With intact epithelium, the vocal folds exhibited a symmetrical vibration pattern with complete glottal closure during vibration. The epithelium was then enzymatically removed from one, then both vocal folds, which led to left-right asymmetric vibration and a decreased closed quotient. Although the mechanisms underlying these vibratory changes are unclear, these results demonstrate that some component of an intact surface layer may play an important role in achieving normal symmetric vibration and glottal closure. PMID:26233062

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

    PubMed

    Liang, Xian-Liang; Liang, Jian-Hui

    2015-07-01

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

  20. Overexpression of FOXO3, MYD88, and GAPDH Identified by Suppression Subtractive Hybridization in Esophageal Cancer Is Associated with Autophagy.

    PubMed

    Soltany-Rezaee-Rad, Mohammad; Mottaghi-Dastjerdi, Negar; Setayesh, Neda; Roshandel, Gholamreza; Ebrahimifard, Farzaneh; Sepehrizadeh, Zargham

    2014-01-01

    To find genes involved in tumorigenesis and the development of esophageal cancer, the suppression subtractive hybridization (SSH) method was used to identify genes that are overexpressed in esophageal cancer tissues compared to normal esophageal tissues. In our SSH library, the forkhead box O3 (FOXO3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and myeloid differentiation primary response 88 (MYD88) genes were the most highly upregulated genes, and they were selected for further studies because of their potential role in the induction of autophagy. Upregulation of these genes was also observed in clinical samples using qRT-PCR. In addition, coexpression analysis of the autophagy-related genes Beclin1, ATG12, Gabarapl, PIK3C3, and LC3 demonstrated a significant correlation between the differentially overexpressed genes and autophagy. Autophagy is an important mechanism in tumorigenesis and the development of chemoresistance in cancer cells. The upregulation of FOXO3, GAPDH, and MYD88 variants in esophageal cancer suggests a role for autophagy and provides new insight into the biology of esophageal cancer. We propose that FOXO3, GAPDH, and MYD88 are novel targets for combating autophagy in esophageal cancer.

  1. Duodenal-content reflux into the esophagus leads to expression of Cdx2 and Muc2 in areas of squamous epithelium in rats.

    PubMed

    Pera, Manuel; Pera, Miguel; de Bolós, Carmen; Brito, Maria J; Palacín, Antonio; Grande, Luis; Cardesa, Antonio; Poulsom, Richard

    2007-07-01

    The molecular events responsible for the transdifferentiation of epithelial cells of the esophagus to a columnar cell type are not well understood. Cdx2 has been detected in Barrett's esophagus, so we sought evidence of Cdx2 expression during the process of transdifferentiation of the esophageal squamous epithelium into a glandular phenotype. Thirty-two rats underwent an esophago-jejunostomy to produce esophagitis of 20, 25, 30, or 35 weeks of duration. The spectrum of esophageal lesions induced by chronic reflux was examined for expression of Cdx2 and Muc2 by immunohistochemistry. Five animals developed glandular metaplasia and adenosquamous carcinoma, two developed only glandular metaplasia, and two had adenosquamous carcinoma alone. Nuclear Cdx2 expression was detected in 57% (four of seven) and 43% (three of seven) of foci of glandular metaplasia and adenosquamous carcinomas, respectively. Cdx2 staining was detectable in some squamous and some mucus secreting cells. Perinuclear and perivacuolar staining of Muc2 was detected focally in 71% (five of seven) and 57% (four of seven) of areas with glandular metaplasia and adenosquamous carcinoma, respectively. We show that duodenal-content reflux into the esophagus switches on the expression of Cdx2 protein in esophageal keratinocytic cells, promoting a mucinous transdifferentiation process with secretion of intestinal mucin Muc2.

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

    PubMed

    Liu, Jiayi; Li, Ning; Li, Li; Li, Danye; Liu, Kai; Zhao, Lingyun; Tang, Jintian; Li, Liya

    2013-12-01

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

  3. In vivo diagnosis of esophageal cancer using image-guided Raman endoscopy and biomolecular modeling.

    PubMed

    Bergholt, M S; Zheng, W; Lin, K; Ho, K Y; Teh, M; Yeoh, K G; So, J B; Huang, Z

    2011-04-01

    The aim of this work was to evaluate the biochemical foundation and clinical merit of multimodal image-guided Raman endoscopy technique for real-time in vivo diagnosis of cancer in the esophagus during clinical endoscopic examinations. A novel fiber-optic Raman endoscopy system was utilized for in vivo esophageal Raman measurements at 785 nm laser excitation within 0.5 second under the multimodal wide-field endoscopic imaging (white light reflectance (WLR) imaging, narrow-band imaging (NBI) and autofluorescence imaging (AFI) guidance. A total of 75 esophageal tissue sites from 27 patients were measured, in which 42 in vivo Raman spectra were from normal tissues and 33 in vivo Raman spectra were from malignant tumors as confirmed by histopathology. The biomolecular modeling (non-negativity-constrained least-squares minimization (NNCLSM) utilizing six basis reference spectra from the representative biochemicals (i.e., actin, collagen, DNA, histones, triolein and glycogen) were employed to estimate the biochemical compositions of esophageal tissue. The resulting diagnostically significant fit coefficients were further utilized through linear discriminant analysis (LDA) and leave-one tissue site-out, cross validation method to develop diagnostic algorithms for esophageal cancer diagnosis. High-quality in vivo Raman spectra in the range of 800-1800 cm-1 can be acquired from normal and cancerous esophageal mucosa in real-time under multimodal endoscopic imaging guidance. Esophageal cancer tissue showed distinct Raman signals mainly associated with cell proliferation, lipid reduction, abnormal nuclear activity and neovasculation. The fit coefficients for actin, DNA, histones, triolein, and glycogen were found to be most significant for construction of the LDA diagnostic model, giving rise to an accuracy of 96.0% (i.e., sensitivity of 97.0% and specificity of 95.2%) for in vivo diagnosis of esophageal cancer. This study demonstrates that multimodal image-guided Raman

  4. Esophageal transit scintigraphy in systemic sclerosis

    PubMed Central

    Kobylecka, Małgorzata; Olesińska, Marzena

    2016-01-01

    Systemic sclerosis is a rare connective tissue disease, distinctive features of which are fibrosis and microangiopathy. The esophagus is one of the most commonly involved internal organs. Most patients experience dysphagia, difficulties in swallowing and gastro-esophageal reflux. However, in up to one third of cases, the initial onset of esophageal disease may be clinically silent. There are several diagnostic modalities available for assessing both morphological and functional abnormalities of the esophagus. If structural abnormalities are suspected, endoscopy is the method of choice. Functional evaluation is best achieved with manometry. Both endoscopy and manometry are invasive techniques, with low patient acceptance. Barium-contrast study is well tolerated, but qualitative assessment of functional abnormalities is imprecise. Esophageal scintigraphy is an easy, non-invasive, sensitive and specific diagnostic modality. It can detect esophageal dysfunction even in asymptomatic patients. In patients already diagnosed with systemic sclerosis, scintigraphy is useful in evaluating severity and progression of the disease. PMID:27994270

  5. Esophageal transit scintigraphy in systemic sclerosis.

    PubMed

    Chojnowski, Marek; Kobylecka, Małgorzata; Olesińska, Marzena

    2016-01-01

    Systemic sclerosis is a rare connective tissue disease, distinctive features of which are fibrosis and microangiopathy. The esophagus is one of the most commonly involved internal organs. Most patients experience dysphagia, difficulties in swallowing and gastro-esophageal reflux. However, in up to one third of cases, the initial onset of esophageal disease may be clinically silent. There are several diagnostic modalities available for assessing both morphological and functional abnormalities of the esophagus. If structural abnormalities are suspected, endoscopy is the method of choice. Functional evaluation is best achieved with manometry. Both endoscopy and manometry are invasive techniques, with low patient acceptance. Barium-contrast study is well tolerated, but qualitative assessment of functional abnormalities is imprecise. Esophageal scintigraphy is an easy, non-invasive, sensitive and specific diagnostic modality. It can detect esophageal dysfunction even in asymptomatic patients. In patients already diagnosed with systemic sclerosis, scintigraphy is useful in evaluating severity and progression of the disease.

  6. Eosinophilic Esophagitis (EE) or (EoE)

    MedlinePlus

    ... in the esophagus. One example is acid reflux . Proton-pump inhibitors (PPIs) are medications that help reduce ... other conditions caused by too much stomach acid. Proton-pump inhibitor responsive esophageal eosinophilia or PPI-REE ...

  7. Multidisciplinary management for esophageal and gastric cancer

    PubMed Central

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

    2016-01-01

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

  8. Tracheoesophageal fistula and esophageal atresia repair

    MedlinePlus

    ... lungs. These defects usually occur together: Esophageal atresia (EA) occurs when the upper part of the esophagus ... have other birth defects beside TEF and/or EA may not be able to have surgery until ...

  9. Regenerative Medicine Strategies for Esophageal Repair

    PubMed Central

    Londono, Ricardo

    2015-01-01

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

  10. Another Obesity Downside: Higher Esophageal Cancer Risk

    MedlinePlus

    ... In the United States, esophageal cancer is rare, accounting for only 1 percent of all new cancers ... advanced stage. Stomach cancer, likewise, is also rare, accounting for fewer than 2 percent of all new ...

  11. Managing eosinophilic esophagitis: challenges and solutions

    PubMed Central

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

    2016-01-01

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

  12. Treatment Options by Stage (Esophageal Cancer)

    MedlinePlus

    ... layers of tissue , including mucous membrane , muscle, and connective tissue . Esophageal cancer starts on the inside lining of ... and spread into the muscle layer or the connective tissue layer of the esophagus wall. The cancer cells ...

  13. Esophageal papilloma: Flexible endoscopic ablation by radiofrequency

    PubMed Central

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

    2015-01-01

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

  14. Esophageal dysmotility is present before surgery in isolated tracheoesophageal fistula.

    PubMed

    Lemoine, Caroline; Aspirot, Ann; Morris, Melanie; Faure, Christophe

    2015-05-01

    After surgical correction of esophageal atresia with or without tracheoesophageal fistula, esophageal body motility dysfunction has been reported in nearly all patients. Using high-resolution esophageal manometry before surgical repair in 2 children with isolated tracheoesophageal fistula, we sought to determine whether dysmotility was present before any surgical insult to test the hypothesis that dysmotility associated with esophageal atresia with or without tracheoesophageal fistula is related to intrinsic primary factors linked to abnormal development of the esophagus. Both had an abnormal esophageal motility: one exhibited hypomotility with distal contraction, whereas the other showed a complete aperistalsis pattern. This suggests that esophageal dysmotility is congenital in nature rather than secondary to surgery.

  15. Clinical application of endoscopic ultrasonography for esophageal achalasia.

    PubMed

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

    2015-04-01

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

  16. Connexins form functional hemichannels in porcine ciliary epithelium.

    PubMed

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

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

  17. Cell cycle of globose basal cells in rat olfactory epithelium.

    PubMed

    Huard, J M; Schwob, J E

    1995-05-01

    The olfactory epithelium of adult mammals has the unique property of generating olfactory sensory neurons throughout life. Cells of the basal compartment, which include horizontal and globose basal cells, are responsible for the ongoing process of neurogenesis in this system. We report here that the globose basal cells in olfactory epithelium of rats, as in mice, are the predominant type of proliferating cell, and account for 97.6% of the actively dividing cells in the basal compartment of the normal epithelium. Globose basal cells have not been fully characterized in terms of their proliferative properties, and the dynamic aspects of neurogenesis are not well understood. As a consequence, it is uncertain whether cell kinetic properties are under any regulation that could affect the rate of neurogenesis. To address this gap in our knowledge, we have determined the duration of both the synthesis phase (S-phase) and the full cell cycle of globose basal cells in adult rats. The duration of the S-phase was found to be 9 hr in experiments utilizing sequential injections of either IdU followed by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined by varying the time interval between the injections of 3H-thy and BrdU and tracking the set of cells that exit S shortly after the first injection. With this paradigm, the interval required for these cells to traverse G2, M, G1, and a second S-phase, is equivalent to the duration of one mitotic cycle and equals 17 hr. These observations serve as the foundation to assess whether the cell cycle duration is subject to regulation in response to experimental injury, and whether such regulation is partly responsible for changes in the rate of neurogenesis in such settings.

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

    SciTech Connect

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

    2010-05-14

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

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

    PubMed Central

    Walker, Nancy M.; Liu, Jinghua; Stein, Sydney R.; Stefanski, Casey D.; Strubberg, Ashlee M.

    2015-01-01

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

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

    PubMed

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

    2016-01-15

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

  1. Classification of Esophageal Strictures following Esophageal Atresia Repair.

    PubMed

    Macchini, Francesco; Parente, Giovanni; Morandi, Anna; Farris, Giorgio; Gentilino, Valerio; Leva, Ernesto

    2017-03-06

    Introduction The aim of this study was to stratify anastomotic strictures (AS) following esophageal atresia (EA) repair and to establish predictors for the need of dilations. Material and Methods A retrospective study on children operated on for EA between 2004 and 2014 was conducted. The stricture index (SI) was measured both radiologically (SIXR) and endoscopically (SIEND). A correlation analysis between the SI and the number of dilations was performed using Spearman's test and linear regression analysis. Results In this study, 40 patients were included: 35 (87.5%) presented with Gross's type C EA, 3 (7.5%) type A, 1 (2.5%) type B, and 1 (2.5%) type D. The mean follow-up time was 101 ± 71.1 months (range: 7.8-232.5, median: 97.6). The mean SIXR was 0.56 ± 0.16 (range: 0.15-0.86). The mean SIEND was 0.45 ± 0.22 (range: 0.15-0.85). Twenty-four patients (60%) underwent a mean of 2 endoscopic dilations (range: 1-9). The number of dilations was poorly correlated with SIXR, while significantly correlated with SIEND. Patients who did not need dilations had a SIEND < 0.33, patients who needed only one dilation had 0.33 ≤ SIEND < 0.44, and those with SIEND ≥ 0.44 needed two or more dilations. No significant association with other clinical variables was found. All patients were asymptomatic at the time of the first endoscopy. Conclusion SIEND is a useful tool to classify AS and can represent a predictor of the need for endoscopic dilation. The role of the SIEND becomes even more important as clinical characteristics have a low predictive value for the development of an AS and the need for subsequent endoscopic esophageal dilatations.

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

    SciTech Connect

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

    2015-06-15

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

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

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Role of diagnostic tests in esophageal evaluation

    SciTech Connect

    Silverstein, B.D.; Pope, C.E. II

    1980-06-01

    In the evaluation of esophageal disease, the appropriate question must be asked before the correct tests can be selected. Reflux can be demonstrated by radiologic methods, pH testing or radioisotopic techniques. Esophageal mucosal damage is best evaluated by x-ray, endoscopy, or biopsy. Chest pain is demonstrated by acid infusion or by manometry. Two algorithms are presented for the evaluation of chest pain and reflux symptoms.

  6. Effect of total laryngectomy on esophageal motility

    SciTech Connect

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

    1981-01-01

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

  7. Diagnosis and management of esophageal achalasia.

    PubMed

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

    2016-09-13

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

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

    PubMed

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

    2015-08-01

    CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.

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

    PubMed Central

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

    1991-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  11. Immunohistochemical characteristics of normal canine eyes.

    PubMed

    Labelle, P; Reilly, C M; Naydan, D K; Labelle, A L

    2012-09-01

    Immunohistochemistry is widely utilized in diagnostic laboratories to study neoplastic and nonneoplastic diseases. Knowledge of the immunohistochemical characteristics of normal tissue is essential for interpretation of immunoreactivity in pathologic conditions. In this study, immunohistochemistry was performed with a broad panel of diagnostically relevant antibodies on 4 normal canine globes--namely, vimentin, pan-cytokeratin (AE1/AE3), cytokeratin 7, cytokeratin 8/18, cytokeratin 20, α-smooth muscle actin, muscle specific actin, desmin, Melan-A, microphthalmia transcription factor, S-100, glial fibrillary acidic protein, triple neurofilaments, neuron-specific enolase, chromogranin A, synaptophysin, laminin and CD31. Results include cytokeratin immunoreactivity limited to the conjunctival epithelium, corneal epithelium, and retinal pigment epithelium; distinct patterns of immunopositivity of muscle markers; and widespread immunoreactivity for vimentin and most neural/neuroendocrine markers. These findings in normal eyes provide the basis for interpretation of ocular immunohistochemistry in dogs. Published immunophenotypes of primary ocular neoplasms are also reviewed.

  12. Interventional Therapy of Esophageal Cancer

    PubMed Central

    Mao, Aiwu

    2016-01-01

    Esophageal cancer (EC) is the fourth leading cause of cancer death in China. Despite a lot of advances in diagnosis and therapy, the survival rate of patients with EC is low. There is urgent need for a variety of methods and techniques to improve the survival time and alleviate the lesions of EC. Nowadays, alternative and less invasive approaches to the treatment of ECs are being identified. Here, we review several main interventional methods at different stages of EC, including endoscopic resection, stent placement, arterial infusion, photodynamic therapy, and radiofrequency ablation. This review will focus on the indications, methods, clinical outcomes, and complications of these methods, which may help guide the way forward. PMID:27904858

  13. A weakly acidic solution containing deoxycholic acid induces esophageal epithelial apoptosis and impairs integrity in an in vivo perfusion rabbit model

    PubMed Central

    Pardon, Nicolas A.; Vicario, Maria; Vanheel, Hanne; Vanuytsel, Tim; Ceulemans, Laurens J.; Vieth, Michael; Jimenez, Marcel; Tack, Jan

    2016-01-01

    Impaired esophageal mucosal integrity may be an important contributor in the pathophysiology of gastroesophageal reflux disease (GERD). Nevertheless, the effect of potentially harmful agents on epithelial integrity is mainly evaluated in vitro for a short period of time and the possible induction of epithelial apoptosis has been neglected. Our objective was to assess the effect of an acidic and weakly acidic solution containing deoxycholic acid (DCA) on the esophageal epithelium in an in vivo rabbit model of esophageal perfusion and to evaluate the role of the epithelial apoptosis. The esophagus of 55 anesthetized rabbits was perfused for 30 min with different solutions at pH 7.2, pH 5.0, pH 1.0, and pH 5.0 containing 200 and 500 μM DCA. Thereafter, animals were euthanized immediately or at 24 or 48 h after the perfusion. Transepithelial electrical resistance, epithelial dilated intercellular spaces, and apoptosis were assessed in Ussing chambers, by transmission electron microscopy, and by TUNEL staining, respectively. No macroscopic or major microscopic alterations were observed after the esophageal perfusions. The acidic and weakly acidic solution containing DCA induced similar long-lasting functional impairment of the epithelial integrity but different ultrastructural morphological changes. Only the solution containing DCA induced epithelial apoptosis in vivo and in vitro in rabbit and human tissue. In contrast to acid, a weakly acidic solution containing DCA induces epithelial apoptosis and a long-lasting impaired mucosal integrity. The presence of apoptotic cells in the esophageal epithelium may be used as a marker of impaired integrity and/or bile reflux exposure. PMID:26797397

  14. Impaired visceral sensitivity to acid reflux in patients with Barrett's esophagus. The role of esophageal motility*.

    PubMed

    Byrne, P J; Mulligan, E D; O'Riordan, J; Keeling, P W N; Reynolds, J V

    2003-01-01

    Patients with Barrett's esophagus have been reported to have impaired visceral sensitivity to acid perfusion and distension compared with non-Barrett's refluxers, but the mechanism is poorly understood. Esophageal motility and clearance mechanisms may be important, and this study explored the relationship of motility with symptoms. Seventy-four patients with Barrett's esophagus were compared with 216 patients with gastro-esophageal reflux disease (GERD) with abnormal acid reflux scores, and 50 symptomatic patients who had normal acid exposure. All patients had esophageal manometry and 24-h pH monitoring. Thirty-six Barrett's patients also had 24-h bile reflux monitoring. Symptoms were assessed by Symptom Index (SI) during 24-h pH monitoring. Barrett's patients with normal motility had a significantly lower SI than GERD patients for similar acid exposure (P < 0.001). Barrett's patients with abnormal motility had higher acid exposure than those with normal motility (P < 0.05), but the SI values for this group was not significantly different from the GERD patients. SI and Bile reflux in Barrett's esophagus was not significantly different in patients with normal or abnormal motility. Barrett's patients had less sensitivity than GERD patients for similar acid exposure. Normal motility in Barrett's esophagus is associated with the poorest sensitivity and the presence of increased acid exposure is required in order to achieve sensitivity levels comparable with GERD patients.

  15. Effect of nitrogen dioxide on human nasal epithelium

    SciTech Connect

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

    1993-09-01

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

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

    NASA Astrophysics Data System (ADS)

    Welsh, Michael J.

    1986-06-01

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

  17. Propagation of normal human epithelial cell populations using an in vivo culture system. Description and applications.

    PubMed Central

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

    1982-01-01

    A new model using xenotransplanted human epithelia was developed for the study of toxic and carcinogenic effects of chemicals. Epithelial cells from the respiratory tract of 4 male and 3 female premature and fullterm fetuses were enzymatically removed and inoculated into deepithelialized rat tracheas. These were sealed at both ends and transplanted subcutaneously into nude mice. After 3-4 weeks, a normal mucociliary epithelium covered the tracheal lumen. At this stage the epithelial cells could be isolated again and transplanted into new denuded rat tracheas. This passaging could be repeated up to six times, each permitting an amplification factor of approximately 3. Tracheal transplants containing cells of human origin (in vivo Passages 2-4) were treated with 7,12-dimethylbenz(a)anthracene. Hyperplasias, squamous metaplasias, and dysplasias were seen 1-8 weeks after initiation of treatment, indicating that the responses of human and rodent epithelial cells to polycyclic aromatic hydrocarbons are similar. Initial experiments with skin and esophageal epithelia suggest that other covering epithelia could also be used in this fashion for evaluation of toxicants and carcinogens that are likely to come into contact with these tissues. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:6821529

  18. Evidence of abnormal esophageal motility in syndrome X by radionuclide esophageal transit test.

    PubMed

    Kao, C H; Hsieh, J F; Tsai, C S; Ho, Y J; Lee, J K

    2000-01-01

    In 30 patients with syndrome X, esophageal motility was evaluated by radionuclide esophageal transit test (RETT). Esophageal motility measurements included esophageal mean transit time (MTT), residual fraction (RF), and retrograde index (RI). In comparison with 25 age- and sex-matched healthy volunteers, 66% of the patients with syndrome X had abnormal RETT findings including 50% of cases with longer MTT, 50% of cases with higher RF, and 33% of cases with higher RI. In addition, the mean values of MTT, RF, and RI in patients with syndrome X were significantly higher than those of healthy volunteers. We conclude that abnormal esophageal motility occurred in a large portion of syndrome X patients based on an simple and noninvasive RETT.

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

    SciTech Connect

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

    1991-06-01

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

  20. Eosinophilic esophagitis after esophageal atresia: is there an association? Case presentation and literature review.

    PubMed

    Gorter, Ramon R; Heij, Hugo A; van der Voorn, J Patrick; Kneepkens, C M Frank

    2012-06-01

    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.

  1. Crural diaphragm inhibition during esophageal distension correlates with contraction of the esophageal longitudinal muscle in cats.

    PubMed

    Liu, Jianmin; Puckett, James L; Takeda, Torahiko; Jung, Hwoon-Yong; Mittal, Ravinder K

    2005-05-01

    Esophageal distension causes simultaneous relaxation of the lower esophageal sphincter (LES) and crural diaphragm. The mechanism of crural diaphragm relaxation during esophageal distension is not well understood. We studied the motion of crural and costal diaphragm along with the motion of the distal esophagus during esophageal distension-induced relaxation of the LES and crural diaphragm. Wire electrodes were surgically implanted into the crural and costal diaphragm in five cats. In two additional cats, radiopaque markers were also sutured into the outer wall of the distal esophagus to monitor esophageal shortening. Under light anesthesia, animals were placed on an X-ray fluoroscope to monitor the motion of the diaphragm and the distal esophagus by tracking the radiopaque markers. Crural and costal diaphragm electromyograms (EMGs) were recorded along with the esophageal, LES, and gastric pressures. A 2-cm balloon placed 5 cm above the LES was used for esophageal distension. Effects of baclofen, a GABA(B) agonist, were also studied. Esophageal distension induced LES relaxation and selective inhibition of the crural diaphragm EMG. The crural diaphragm moved in a craniocaudal direction with expiration and inspiration, respectively. Esophageal distension-induced inhibition of the crural EMG was associated with sustained cranial motion of the crural diaphragm and esophagus. Baclofen blocked distension-induced LES relaxation and crural diaphragm EMG inhibition along with the cranial motion of the crural diaphragm and the distal esophagus. There is a close temporal correlation between esophageal distension-mediated LES relaxation and crural diaphragm inhibition with the sustained cranial motion of the crural diaphragm. Stretch caused by the longitudinal muscle contraction of the esophagus during distension of the esophagus may be important in causing LES relaxation and crural diaphragm inhibition.

  2. Clinical and dosimetric factors of radiation-induced esophageal injury: Radiation-induced esophageal toxicity

    PubMed Central

    Qiao, Wen-Bo; Zhao, Yan-Hui; Zhao, Yan-Bin; Wang, Rui-Zhi

    2005-01-01

    AIM: To analyze the clinical and dosimetric predictive factors for radiation-induced esophageal injury in patients with non-small-cell lung cancer (NSCLC) during three-dimensional conformal radiotherapy (3D-CRT). METHODS: We retrospectively analyzed 208 consecutive patients (146 men and 62 women) with NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35-87 years). The clinical and treatment parameters including gender, age, performance status, sequential chemotherapy, concurrent chemotherapy, presence of carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the entire esophagus, maximal point dose to the esophagus, and percentage of volume of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for radiation-induced acute and late grade 3-5 esophageal injury were analyzed according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Twenty-five (12%) of the two hundred and eight patients developed acute or late grade 3-5 esophageal injury. Among them, nine patients had both acute and late grade 3-5 esophageal injury, two died of late esophageal perforation. Concurrent chemotherapy and maximal point dose to the esophagus ≥60 Gy were significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four (26%) of the two hundred and eight patients received concurrent chemotherapy. Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01). However, no grade 3-5 esophageal injury occurred in patients who received a maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). CONCLUSION: Concurrent chemotherapy and the maximal esophageal point dose ≥60 Gy are significantly associated with the risk of grade 3-5 esophageal injury in patients with NSCLC treated with 3D-CRT. PMID:15849822

  3. Blunt traumatic esophageal injury: Unusual presentation and approach☆

    PubMed Central

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

    2013-01-01

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

  4. Endoscopic submucosal dissection for early esophageal cancer associated with achalasia.

    PubMed

    Ohkura, Yu; Iizuka, Toshiro; Kikuchi, Daisuke; Yamashita, Satoshi; Nakamura, Masanori; Matsui, Akira; Mitani, Toshifumi; Hoteya, Shu; Kaise, Mitsuru; Yahagi, Naohisa

    2013-01-01

    Esophageal achalasia is often associated with esophageal cancer. However, in many cases, esophageal cancer tends to be found in an advanced stage, with a poor prognosis. However, early-stage cancer was detected recently due to the advances in endoscopic instruments. In those cases, it is important to facilitate successful treatment by endoscopic submucosal dissection. We analyzed a total of six cases of esophageal cancer with achalasia in four patients treated with endoscopic submucosal dissection. Three features common to all six cases had a bearing on how endoscopic submucosal dissection was performed. First, esophageal dilatation and diminished peristalsis facilitated the performance of successful endoscopic submucosal dissection. Second, the esophageal wall was thickened, primarily with muscular tissue. Third, the submucosal layer contained abundant blood vessels that made it difficult to minimize bleeding during dissection. Those findings suggest that endoscopic submucosal dissection for early esophageal cancer associated with achalasia is a safe and potentially curative procedure. It is important, therefore, to detect esophageal cancer early.

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

    PubMed

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

    2016-01-01

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

  6. Broken Esophageal Stent Successfully Treated by Interventional Radiology Technique

    SciTech Connect

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

    2010-06-15

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

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

    PubMed

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

    2012-09-01

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

  8. Chemoprevention of esophageal squamous cell carcinoma

    SciTech Connect

    Stoner, Gary D. Wang Lishu; Chen Tong

    2007-11-01

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

  9. Evaluation of urgent esophagectomy in esophageal perforation

    PubMed Central

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

    2014-01-01

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

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

    SciTech Connect

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

    1993-05-01

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

  11. Immunoglobulin deposits in labial mucosal epithelium of patients suspected of Sjögren's syndrome.

    PubMed

    Oxholm, P; Manthorpe, R; Oxholm, A; Schiødt, M

    1986-02-01

    Lower lip biopsies from twenty-three consecutive patients under evaluation for Sjögren's syndrome, and from six normal controls, were investigated for deposits of immunoglobulins, fibrinogen and C3, using a direct immunofluorescence technique. Deposits of both IgG and IgA were demonstrated in the mucosal epithelium in three of six patients with primary Sjögren's syndrome. Similar IgG deposits were found in two of three patients with xerostomia and in one of three patients with Sjögren's syndrome secondary to rheumatoid arthritis. Immunoglobulins were located in close relation to cell surfaces in the basal and suprabasal layers of the epithelium. Double labelling experiments indicated a partial topographic concordance between the immunoglobulin deposits and OKT6 positive Langerhans cells in the epithelium. No deposits of immunoglobulins, fibrinogen or C3 were found in the remaining eleven patients and six normal controls. We conclude that deposits of IgG and IgA in the labial mucosal epithelium seem to be a characteristic finding in patients with primary Sjögren's syndrome as well as in patients with xerostomia. The diagnostic value of this new observation needs to be clarified in future studies.

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

    PubMed

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

    2014-01-01

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

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

    PubMed

    Chen, Keneng

    2014-09-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Retinal pigment epithelium engineering using synthetic biodegradable polymers.

    PubMed

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

    2001-12-01

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

  16. X-ray microanalysis of hamster tracheal epithelium

    SciTech Connect

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

    1989-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  18. Mechanically patterning the embryonic airway epithelium.

    PubMed

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

    2015-07-28

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

  19. Odors Discrimination by Olfactory Epithelium Biosensor

    NASA Astrophysics Data System (ADS)

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

    2011-09-01

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

  20. [Neutrophils and monocytes in gingival epithelium

    PubMed

    Meng, H X; Zheng, L P

    1994-06-01

    Neutrophils and monocytes of gingival epithellium in health gingiva(H),marginal gingivitis(MG),juvenile periodontitis(JP),adult periodontitis(AP) and subgingival bacteria were quantitated and analyzed,The results showed that the numbers of PMN within either pocket epithelium or oral gingival epithelium in JP were significantly lower than in AP and G.The amounts of PMN in AP were much larger than other three groups.Positive correlation between the number of PMN in sulcular pocket epitelium and the motile bacteri of subgingival plaque was demonstrated by correlation analysis.Monocytes mainly presented in deep pocket and junctional epithelum which were stained by NAE method,however very few Langhans cells were seen in these areas.

  1. Mechanically patterning the embryonic airway epithelium

    PubMed Central

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

    2015-01-01

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

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

    ClinicalTrials.gov

    2016-09-15

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

  3. Proton Beam Therapy and Concurrent Chemotherapy for Esophageal Cancer

    SciTech Connect

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

    2012-07-01

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

  4. Use of glucagon in relieving esophageal food bolus impaction in the era of eosinophilic esophageal infiltration.

    PubMed

    Thimmapuram, Jayaram; Oosterveen, Scott; Grim, Rodney

    2013-06-01

    Esophageal food bolus impaction may require an urgent endoscopy. Glucagon is often administered to promote spontaneous passage of the food bolus. Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia, and food impaction is often the presenting symptom. Our study was aimed at determining the effectiveness of glucagon in relieving esophageal foreign body obstruction in general and in the setting of esophageal eosinophilic infiltration (EEI). A retrospective chart review was performed using the ICD codes and the emergency department database of adult patients presenting with symptoms of esophageal food bolus impaction from July 2004 to October 2010. Response to glucagon was defined as symptomatic relief of obstruction prior to endoscopic intervention. A total of 213 episodes of esophageal food bolus obstruction in 192 patients were identified during the study period. Glucagon was given in 125 cases of which 41 had a response (32.8 %). A total of 170 episodes had an Esophagogastroduodenoscopy performed either during the impaction event or at a later date. Of the 60 patients' biopsies, 45 had received glucagon (17 with EEI, 28 without EEI). None of the 17 episodes with EEI as compared to 8 of the 28 without EEI responded to glucagon (0 % vs. 28.5 %, p = 0.017). Glucagon is effective in about one third of patients with esophageal food bolus impaction, which is consistent with historical data. Patients with EEI appear less likely to respond to glucagon.

  5. Esophageal surgery in minimally invasive era

    PubMed Central

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

    2016-01-01

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

  6. Management of Esophageal Perforation in Adults

    PubMed Central

    Kaman, Lileswar; Iqbal, Javid; Kundil, Byju; Kochhar, Rakesh

    2010-01-01

    Perforation of esophagus in the adult is a very morbid condition with high morbidity and mortality. The ideal treatment is controversial. The main causes for esophageal perforation in adults are iatrogenic, traumatic, spontaneous and foreign bodies. The morbidity and mortality rate is directly related to the delay in diagnosis and initiation of optimum treatment. The reported mortality from treated esophageal perforation is 10% to 25%, when therapy is initiated within 24 hours of perforation, but it could rise up to 40% to 60% when the treatment is delayed beyond 48 hours. Primary closure of the perforation site and wide drainage of the mediastinum is recommended if perforation is detected in less than 24 hours. Treatment option for delayed or missed rupture of esophagus is not very clear and is controversial. Recently a substantial number of patients with esophageal perforation are being managed by nonoperative measures. Patients with small perforations and minimal extraesophageal involvement may be better managed by nonoperative treatment Major prognostic factors determining mortality are the etiology and site of the injury, the presence of underlying esophageal pathology, the delay in diagnosis and the method of treatment. For optimum outcome for management of esophageal perforations in adults a multidisciplinary approach is needed. PMID:27942303

  7. The Tumor Microenvironment in Esophageal Cancer

    PubMed Central

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

    2016-01-01

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

  8. Altered Esophageal Mucosal Structure in Patients with Celiac Disease

    PubMed Central

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

    2016-01-01

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

  9. Identification of human papillomavirus in esophageal squamous papillomas

    PubMed Central

    Bohn, Olga L; Navarro, Leticia; Saldivar, Jesus; Sanchez-Sosa, Sergio

    2008-01-01

    AIM: To investigate the presence of human papillomavirus (HPV) in esophageal squamous papilloma (ESP) and determine p16, p53 and Ki67 expression in a Mexican cohort. METHODS: Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by amplified chromogenic in situ hybridization (ACISH) using a wide spectrum-cocktail probe and PCR. RESULTS: The average age at presentation was 46.3 years (range 28-72 years). Patients included four (22.22%) males and 14 (77.77%) females. The most frequent location was upper third (11 cases), followed by middle third (3 cases) and unknown site (5 cases). Immunohistochemistry (IHC) revealed basal and focal p53 expression in 17 cases (89%); p16 was expressed in eight cases (42.10%) and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases (87.5%) by ACISH: Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases (85.7%). Low-risk HPV types were detected in the most of the cases. CONCLUSION: This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESP. PMID:19084918

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

    PubMed

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

    2016-07-01

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

  11. Overexpression of human β-defensin 2 promotes growth and invasion during esophageal carcinogenesis.

    PubMed

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

    2014-11-30

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

  12. CCN1 Induces β-Catenin Translocation in Esophageal Squamous Cell Carcinoma through Integrin α11.

    PubMed

    Chai, Jianyuan; Modak, Cristina; Ouyang, Yi; Wu, Sing-Yung; Jamal, M Mazen

    2012-01-01

    Aims. Nuclear translocation of β-catenin is common in many cancers including esophageal squamous cell carcinoma (ESCC). As a mediator of Wnt signaling pathway, nuclear β-catenin can activate many growth-related genes including CCN1, which in turn can induce β-catenin translocation. CCN1, a matricellular protein, signals through various integrin receptors in a cell-dependent manner to regulate cell adhesion, proliferation, and survival. Its elevation has been reported in ESCC as well as other esophageal abnormalities such as Barrett's esophagus. The aim of this study is to examine the relationship between CCN1 and β-catenin in ESCC. Methods and Results. The expression and correlation between CCN1 and β-catenin in ESCC tissue were examined through immunohistochemistry and further analyzed in both normal esophageal epithelial cells and ESCC cells through microarray, functional blocking and in situ protein ligation. We found that nuclear translocation of β-catenin in ESCC cells required high level of CCN1 as knockdown of CCN1 in ESCC cells reduced β-catenin expression and translocation. Furthermore, we found that integrin α(11) was highly expressed in ESCC tumor tissue and functional blocking integrin α(11) diminished CCN1-induced β-catenin elevation and translocation. Conclusions. Integrin α(11) mediated the effect of CCN1 on β-catenin in esophageal epithelial cells.

  13. Decreased Tumor Suppressor Candidate 3 Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma.

    PubMed

    Yu, Xinshuang; Zhang, Jiandong; Zhong, Hua; Liu, Fengjun; Liang, Ning; Wang, Yao; Meng, Xiangjiao; Du, Juan

    2016-01-01

    TUSC3 was recently identified as a potential tumor suppressor gene in a variety of human malignancies. However, no data are currently available regarding the expressions of TUSC3 in esophageal cancer (ESCC).The purposes of this study was to investigated the expressions of TUSC3 in ESCC tissues and assess the relationship between TUSC3 levels and clinico-pathological characteristics of ESCC patients. TUSC3 protein expressions were evaluated by immunohistochemistry (IHC) on tissue microarray slides in esophageal cancer, which included 95 esophageal squamous carcinoma specimens (ESCC), and 75 normal esophageal mucosa (NEM). We found that TUSC3 in ESCC was significant lower than that in NEM (P=0.000). According to multi-clinical classifications, TUSC3 level varied significantly with TNM stage, T stage, and N stage (p<0.001, p=0.0368, p<0.0001, respectively). Univariate analysis showed that gender, TNM stage, T stage, N stage, TUSC3 expression were prognostic factors for survival. Multivariate analysis showed that in our study, only TUSC3 expression was independent prognostic factors for ESCC. Our results indicated for the first time, a combined analysis of TUSC3 expressions as well as the clinical variables will help predict the prognosis of ESCC patients. Further large-sample validation and functional analysis should be performed to evaluate its potential prognostic and therapeutic values for ESCC patients.

  14. Comparison of esophageal motility in patients with solid dysphagia and mixed dysphagia.

    PubMed

    Chen, Chien-Lin; Orr, William C

    2005-01-01

    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.

  15. Effects of Age on Esophageal Motility: Use of High-resolution Esophageal Impedance Manometry

    PubMed Central

    Shim, Young Kwang; Kim, Nayoung; Park, Yo Han; Lee, Jong-Chan; Sung, Jihee; Choi, Yoon Jin; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Lee, Dong Ho

    2017-01-01

    Background/Aims Disturbances of esophageal motility have been reported to be more frequent the aged population. However, the physiology of disturbances in esophageal motility during aging is unclear. The aim of this study was to evaluate the effects of age on esophageal motility using high-resolution esophageal impedance manometry (HRIM). Methods Esophageal motor function of 268 subjects were measured using HRIM in 3 age groups, < 40 years (Group A, n = 32), 40–65 years (Group B, n = 185), and > 65 years (Group C, n = 62). Lower esophageal sphincter (LES) and upper esophageal sphincter (UES) pressures, integrated relaxation pressure, distal contractile integral, contractile front velocity, distal latency, and pressures and duration of contraction on 4 positions along the esophagus, and complete bolus transit were measured. Results Basal UES pressure was lower in Group C (P < 0.001) but there was no significant difference in the LES pressure among groups. Contractile duration on position 3 (10 cm from proximal LES high pressure zone) was longer in Group C (P = 0.001), and the contractile amplitude on position 4 (5 cm from proximal LES high pressure zone) was lower in Group C (P = 0.005). Distal contractile integral was lower in Group C (P = 0.037). Contractile front velocity (P = 0.015) and the onset velocity (P = 0.040) was lower in Group C. There was no significant difference in impedance values. Conclusions The decrease of UES pressure, distal esophageal motility, and peristaltic velocity might be related with esophageal symptoms in the aged population. PMID:28163259

  16. Neurogenesis in the vomeronasal epithelium of adult garter snakes: 3. Use of /sup 3/H-thymidine autoradiography to trace the genesis and migration of bipolar neurons

    SciTech Connect

    Wang, R.T.; Halpern, M.

    1988-10-01

    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.

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

    NASA Astrophysics Data System (ADS)

    Richards-Kortum, Rebecca

    2016-03-01

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

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

    PubMed Central

    Singla, Manish B; Moawad, Fouad J

    2016-01-01

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

  19. Endoscopic ultrasonography in the management of esophageal cancer

    NASA Astrophysics Data System (ADS)

    Trowers, Eugene A.

    2000-05-01

    Precise tumor-staging is critical in the management of early esophageal caner. Endoscopic ultrasound (EUS) allows the endoscopist a view beyond the esophageal wall which opens the door to a variety of new gastroenterologic techniques. Endoscopic mucosal resection, laser photoablation and photodynamic therapy may be successfully employed in early esophageal cancer management. Combination radiation therapy and chemotherapy have shown better responses in advanced cancer. Expandable metallic stents may also provide palliation with inoperable esophageal cancer. The efficacy of EUS in the management of esophageal cancer is critically reviewed.

  20. Endoscopic treatment of esophageal achalasia.

    PubMed

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

    2016-01-25

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

  1. 2011 update on esophageal achalasia.

    PubMed

    Chuah, Seng-Kee; Hsu, Pin-I; Wu, Keng-Liang; Wu, Deng-Chyang; Tai, Wei-Chen; Changchien, Chi-Sin

    2012-04-14

    There have been some breakthroughs in the diagnosis and treatment of esophageal achalasia in the past few years. First, the introduction of high-resolution manometry with pressure topography plotting as a new diagnostic tool has made it possible to classify achalasia into three subtypes. The most favorable outcome is predicted for patients receiving treatment for type II achalasia (achalasia with compression). Patients with type I(classic achalasia) and type III achalasia (spastic achalasia) experience a less favorable outcome. Second, the first multicenter randomized controlled trial published by the European Achalasia Trial group reported 2-year follow-up results indicating that laparoscopic Heller myotomy was not superior to endoscopic pneumatic dilation (PD). Although the follow-up period was not long enough to reach a convincing conclusion, it merits the continued use of PD as a generally available technique in gastroenterology. Third, the novel endoscopic technique peroral endoscopic myotomy is a promising option for treating achalasia, but it requires increased experience and cautious evaluation. Despite all this good news, the bottom line is a real breakthrough from the basic studies to identify the actual cause of achalasia that may impede treatment success is still anticipated.

  2. Cellular transformation by cigarette smoke extract involves alteration of glycolysis and mitochondrial function in esophageal epithelial cells.

    PubMed

    Kim, Myoung Sook; Huang, Yiping; Lee, Juna; Zhong, Xiaoli; Jiang, Wei-Wen; Ratovitski, Edward A; Sidransky, David

    2010-07-15

    Cigarette-smoking increases the risk of developing various types of human cancers including esophageal cancers. To test the effects of chronic cigarette smoke exposure directly on esophageal epithelium, cellular resistance to mainstream extract (MSE), or sidestream smoke extract (SSE) was developed in chronically exposed nonmalignant Het-1A cells. Anchorage-independent growth, in vitro invasion capacity and proliferation of the resistant cells increased compared with the unexposed, sensitive cells. An epithelial marker E-cadherin was down-regulated and mesenchymal markers N-cadherin and vimentin were up-regulated in the resistant cells. Het-1A cells resistant to MSE or SSE consumed more glucose, and produced more lactate than the sensitive cells. The increased anchorage-independent cell growth of the resistant cells was suppressed by a glycolysis inhibitor, 2-deoxy-D-glucose, indicating that these cells are highly dependent on the glycolytic pathway for survival. Decreased mitochondrial membrane potential and ATP production in the resistant cells indicate the presence of mitochondrial dysfunction induced by chronic exposure of cigarette smoke extract. Increased expression of nuclear genes in the glycolytic pathway and decreased levels of mitochondrial genes in the resistant cells support the notion that cigarette smoking significantly contributes to the transformation of nonmalignant esophageal epithelial cells into a tumorigenic phenotype.

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

    PubMed

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

    2015-03-20

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

  4. Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype in vitro and malignant features in esophageal squamous cell carcinomas

    PubMed Central

    Li, Yaqing; Li, Xiaoran; Kan, Quancheng; Zhang, Mingzhi; Li, Xiaoli; Xu, Ruiping; Wang, Junsheng; Yu, Dandan; Goscinski, Mariusz Adam; Wen, Jian-Guo; Nesland, Jahn M.; Suo, Zhenhe

    2017-01-01

    Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application. It was further revealed that the UK5099-treated cells became significantly more resistant to chemotherapy and radiotherapy, and the UK5099-treated tumor cells also exhibited stronger invasive capacity compared to the parental cells. In contrast to esophageal squamous epithelium cells, decreased MPC protein expression was observed in a series of 157 human squamous cell carcinomas, and low/negative MPC1 expression predicted an unfavorable clinical outcome. All these results together revealed the potential connection of altered MPC expression/activity with the Warburg metabolic reprogramming and tumor aggressiveness in cell lines and clinical samples. Collectively, our findings highlighted a therapeutic strategy targeting Warburg reprogramming of human esophageal squamous cell carcinomas. PMID:27911865

  5. Esophageal liposarcoma: Well-differentiated rhabdomyomatous type

    PubMed Central

    Valiuddin, Hisham M; Barbetta, Arianna; Mungo, Benedetto; Montgomery, Elizabeth A; Molena, Daniela

    2016-01-01

    Rhabdomyomatous well-differentiated esophageal liposarcomas are extremely rare. As of August 2016, only one other such case has been reported in the English-language medical literature. Liposarcomas in general are one of the most common soft tissue neoplasms in adults, but the incidence of primary esophageal liposarcomas is exceptionally low. There have been only 42 reported cases of primary liposarcoma of the esophagus worldwide thus far. These malignancies are harbored within giant fibrovascular polyps, which slowly grow within the esophageal lumen causing obstructing symptoms. We hereby present the case of a 68-year-old male patient who came in with a 2-mo history of worsening intermittent dysphagia, persistent cough, and postprandial retrosternal pain. After an esophagogastroduodenoscopy, a computed tomographic scan, and a diagnostic endoscopy, complete endoscopic resection was performed of the 13 cm × 6 cm × 2.6 cm fibrovascular polyp. A literature review was done and results are presented herein. PMID:28035254

  6. Early esophageal carcinoma treated with intracavitary irradiation

    SciTech Connect

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

    1985-08-01

    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.

  7. Congenital esophageal stenosis owing to tracheobronchial remnants

    PubMed Central

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

    2013-01-01

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

  8. Successful endoscopic hemoclipping of an esophageal perforation.

    PubMed

    Sung, H Y; Kim, J I; Cheung, D Y; Cho, S H; Park, S-H; Han, J-Y; Kim, J K; Han, S W; Choi, K Y; Chung, I S

    2007-01-01

    We describe a case of esophageal perforation that resulted from a fishbone. A 71-year-old man had had a fishbone impacted in the lower esophagus for 2 days. At presentation, the bone was dislodged at endoscopy; one round opening in a deep ulceration was detected when the fishbone was removed. The perforation was closed by endoscopic hemoclipping, after the removal of the fishbone. A thoracic computed tomography revealed air around the esophagus, aorta and bronchus and the presence of a pleural effusion. These findings suggested mediastinal emphysema and mediastinitis due to the esophageal perforation after the removal of the fishbone. Esophagography revealed a focal esophageal defect and linear contrast leakage at the distal esophagus. The mediastinal emphysema and pleural effusion successfully resolved after the endoscopic hemoclip application and conservative management of the perforation.

  9. Phenobarbital-responsive sialadenosis associated with an esophageal foreign body in a dog.

    PubMed

    Gilor, Chen; Gilor, Shir; Graves, Thomas K

    2010-01-01

    A 4-year-old Yorkshire terrier was presented for an esophageal foreign body. After removal of the foreign body, clinical signs of gagging, regurgitation, and vomiting continued unabated for >6 weeks. The dog had enlarged submandibular salivary glands that were histologically normal. Treatment with phenobarbital resulted in a rapid and dramatic resolution of clinical signs. After 3 months, the dog was weaned of phenobarbital and was free of any signs of disease 6 months later.

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

    Xiao, Bin

    2016-01-01

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

  12. Esophageal web in Plummer-Vinson syndrome.

    PubMed

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

    1988-09-01

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

  13. Steroid treatment of eosinophilic esophagitis in adults.

    PubMed

    Alexander, Jeffrey A

    2014-06-01

    Topical steroid therapy has been used to treat eosinophilic esophagitis (EoE) for more than 15 years. We review the treatment trials of topical steroid therapy in adult patients with EoE. Currently, there is no commercially available preparation designed to deliver the steroid to the esophagus. Current regimens consist of swallowing steroid preparations designed for inhalation treatment for asthma. In the short term, steroids are associated with an approximately 15% to 25% incidence of asymptomatic esophageal candidiasis, but otherwise appear to be well tolerated.

  14. Eosinophilic esophagitis in adults: An update

    PubMed Central

    Ahmed, Monjur

    2016-01-01

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

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

    SciTech Connect

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

    1985-05-01

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

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

    PubMed

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

    2015-10-01

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

  17. Modulating Effect of Peptide Therapy on the Morphofunctional State of Bronchial Epithelium in Rats with Obstructive Lung Pathology.

    PubMed

    Kuzubova, N A; Lebedeva, E S; Dvorakovskaya, I V; Surkova, E A; Platonova, I S; Titova, O N

    2015-09-01

    On the model of chronic obstructive pulmonary disease, the effect of therapy with low-molecular-weight peptides on restructuring and functional activity of bronchial epithelium for restoring the immune and barrier function of the lungs and prevention of inflammatory process progression was studied. Chronic obstructive pulmonary disease was modeled in rats by 60-day intermittent exposure to NO2. Administration of tetrapeptide Bronchogen for 1 month eliminates symptoms of remodeling of the bronchial epithelium and lung tissue typical of chronic obstructive pulmonary disease (goblet cell hyperplasia, squamous metaplasia, lymphocytic infiltration and emphysema, and restoration of ciliated cells). Enhanced production of secretory IgA, a local immunity marker, attested to normalization of functional activity of bronchial epithelium, while normalization of cell composition and profile of proinflammatory cytokines in the bronchoalveolar space reflected reduction of neutrophilic inflammation.

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

    PubMed Central

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

    2011-01-01

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

  19. Lgr5 regulates the regeneration of lesioned nasal respiratory epithelium.

    PubMed

    Zhang, Yan-Qiang; Li, Peng; Zhang, Feng-Qin; Sun, Shao-Jun; Cao, Yin-Guang

    2016-12-09

    Nasal respiratory epithelium is a ciliated pseudostratified columnar epithelium. The cellular components of nasal respiratory epithelium include ciliated cells, goblet cells, and basal cells. Until now, our knowledge in the development of nasal respiratory epithelium is still limited and the cellular mechanism of regeneration is still elusive. In this study, we found that adult stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is expressed in the mice nasal respiratory epithelium. Both immunostaining and lineage tracing analysis indicated Lgr5 positive cells in the nasal respiratory epithelium are proliferative stem/progenitor cells. Using the Rosa-Tdtomato and Rosa26-DTR mice, we elucidated that Lgr5(+) cells participate in the regeneration of lesioned nasal respiratory epithelium, and this group of cells is necessary in the process of epithelium recovery. Using the in vitro culture system, we observed the formation of spheres from Lgr5(+) cells and these spheres have the capacity to generate other types of cells. Above all, this study reported a group of previously unidentified progenitor/stem cells in nasal respiratory epithelium, unveiling the potential cellular mechanism in nasal respiratory epithelium regeneration.

  20. Identification of a preneoplastic gene expression profile in tubal epithelium of BRCA1 mutation carriers.

    PubMed

    Press, Joshua Z; Wurz, Kaitlyn; Norquist, Barbara M; Lee, Ming K; Pennil, Christopher; Garcia, Rochelle; Welcsh, Piri; Goff, Barbara A; Swisher, Elizabeth M

    2010-12-01

    Microinvasive carcinomas and high-grade intraepithelial neoplasms are commonly discovered within the fallopian tube of BRCA1 mutation carriers at the time of risk-reducing salpingo-oophorectomy, suggesting that many BRCA1-mutated ovarian carcinomas originate in tubal epithelium. We hypothesized that changes in gene expression profiles within the histologically normal fallopian tube epithelium of BRCA1 mutation carriers would overlap with the expression profiles in BRCA1-mutated ovarian carcinomas and represent a BRCA1 preneoplastic signature. Laser capture microdissection of frozen sections was used to isolate neoplastic cells or histologically normal fallopian tube epithelium, and expression profiles were generated on Affymetrix U133 Plus 2.0 gene expression arrays. Normal-risk controls were 11 women wild type for BRCA1 and BRCA2 (WT-FT). WT-FT were compared with histologically normal fallopian tube epithelium from seven women with deleterious BRCA1 mutations who had foci of at least intraepithelial neoplasm within their fallopian tube (B1-FTocc). WT-FT samples were also compared with 12 BRCA1 ovarian carcinomas (B1-CA). The comparison of WT-FT versus B1-FTocc resulted in 152 differentially expressed probe sets, and the comparison of WT-FT versus B1-CA resulted in 4079 differentially expressed probe sets. The BRCA1 preneoplastic signature was composed of the overlap between these two lists, which included 41 concordant probe sets. Genes in the BRCA1 preneoplastic signature included several known tumor suppressor genes such as CDKN1C and EFEMP1 and several thought to be important in invasion and metastasis such as E2F3. The expression of a subset of genes was validated with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry.

  1. Symptom hypersensitivity to acid infusion is associated with hypersensitivity of esophageal contractility.

    PubMed

    Bhalla, Vikas; Liu, Jianmin; Puckett, James L; Mittal, Ravinder K

    2004-07-01

    Several investigators have observed that repeated acid infusions induce stronger symptoms (symptom hypersensitivity). The goal of our study was to determine whether symptom hypersensitivity is associated with esophageal contractile hypersensitivity. Subjects with chronic heartburn symptoms underwent simultaneous pressure and ultrasound imaging of esophagus. Normal saline and 0.1 N HCl were sequentially infused into the esophagus, and subjects scored heartburn symptoms on a 1-10 scale. Saline and HCl infusions were repeated in 10 subjects with a positive Bernstein test. Esophageal contraction amplitude and duration and muscularis propria thickness were measured using a computerized method during recording. Acid infusion induced heartburn. Esophageal contractions had higher amplitudes (pressure 114.2 +/- 7.0%) and longer duration (116.8 +/- 4.4%) during acid infusion compared with saline infusion. Average muscle thickness was greater during acid infusion than saline infusion (107.0 +/- 2.0%). Sustained esophageal contractions (SECs) were identified during acid infusion. A second acid infusion (acid-2) induced heartburn with shorter latency (93.0 +/- 15.0 vs. 317.0 +/- 43.0 s) and stronger severity (8.5 +/- 0.5 vs. 5.3 +/- 0.8) than the first acid infusion (acid-1). Contraction amplitudes (140.2 +/- 13.0%), average muscle thickness (118.0 +/- 3.3%), and contraction duration (148.5 +/- 5.6 vs. 116.8 +/- 4.4%) were higher during acid-2 than acid-1. Also, numbers of SECs were greater during acid-2 than acid-1 (31 in 8 subjects vs. 11 in 6 subjects). Our data show that acid infusion into esophagus induces esophageal hypersensitivity and that a close temporal correlation exists between symptom hypersensitivity and contractility hypersensitivity.

  2. Deletion of JAM-A causes morphological defects in the corneal epithelium.

    PubMed

    Kang, Liang I; Wang, Yan; Suckow, Arthur T; Czymmek, Kirk J; Cooke, Vesselina G; Naik, Ulhas P; Duncan, Melinda K

    2007-01-01

    Junctional adhesion molecule-A (JAM-A, JAM-1, F11R) is an Ig domain containing transmembrane protein that has been proposed to function in diverse processes including platelet activation and adhesion, leukocyte transmigration, angiogenesis, epithelial cell shape and endothelial cell migration although its function in vivo is less well established. In the mouse eye, JAM-A protein expression is first detected at 12.5 dpc in the blood vessels of the tunica vasculosa, while it is first detected in both the corneal epithelium and lens between 13.5 and 14.5 dpc. In the corneal epithelium, JAM-A levels remain appreciable throughout life, while JAM-A immunostaining becomes stronger in the lens as the animals age. Both the cornea and lens of mice lacking an intact JAM-A gene are transparent until at least a year of age, although the cells of the JAM-A null corneal epithelium are irregularly shaped. In wild-type mice, JAM-A protein is found at the leading edge of repairing corneal epithelial wounds, however, corneal epithelial wound repair was qualitatively normal in JAM-A null animals. In summary, JAM-A is expressed in the corneal epithelium where it appears to regulate cell shape.

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

    PubMed Central

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

    2008-01-01

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

  4. Activation of the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway in human cholesteatoma epithelium.

    PubMed

    Liu, Wei; Yin, Tuanfang; Ren, Jihao; Li, Lihua; Xiao, Zian; Chen, Xing; Xie, Dinghua

    2014-02-01

    Cholesteatoma is a benign keratinizing squamous epithelial lesion characterized by the hyper-proliferation of keratinocytes with abundant production of keratin debris in the middle ear. The epidermal growth factor receptor (EGFR)/Akt/nuclear factor-kappa B (NF-κB)/cyclinD1 signaling pathway is one of the most important pathways in regulating cell survival and proliferation. We hypothesized that the EGFR/Akt/NF-κB/cyclinD1 signaling pathway may be activated and involved in the cellular hyperplasia mechanism in acquired cholesteatoma epithelium. Immunohistochemical staining of phosphorylated EGFR (p-EGFR), phosphorylated Akt (p-Akt), activated NF-κB and cyclinD1 protein was performed in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium. Protein expression of p-EGFR, p-Akt, activated NF-κB and cyclinD1 in cholesteatoma epithelium was significantly increased when compared with normal EAC epithelium (p < 0.01). In cholesteatoma epithelium, a significant positive association was observed between p-EGFR and p-Akt expression and between the expressions of p-Akt and NF-κB, NF-κB and cyclinD1, respectively (p < 0.01). No significant relationships were observed between the levels of investigated proteins and the degree of bone destruction (p > 0.05). The increased protein expression of p-EGFR, p-Akt, NF-κB and cyclinD1 and their associations in cholesteatoma epithelium suggest that the EGFR/Akt/NF-κB/cyclinD1 survival signaling pathway is active and may be involved in the regulatory mechanisms of cellular hyperplasia in cholesteatoma epithelium.

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

    PubMed Central

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

    2016-01-01

    AIM To determine the association of p53, carcinoembryonic antigen (CEA) and CA19-9 protein expression with esophageal carcinogenesis. METHODS An iodine staining endoscopic screening program of esophageal lesions was carried out in the high-incidence area of Feicheng County, China. Seventy-seven patients with basal cell hyperplasia (BCH), 247 with low-grade dysplasia (LGD), 51 with high-grade dysplasia (HGD), 134 with invasive cancer, and 80 normal controls diagnosed by mucous membrane biopsy pathology were enrolled. Immunohistochemical detection of p53, CEA and CA19-9 proteins was performed. In the ROC curve analysis, the expression of a single biomarker and the expression of a combination of biomarkers were used to predict the risk of these four esophageal lesions. RESULTS The positive rates of p53 protein expression in invasive cancer, HGD, LGD, BCH and the normal control groups were 53.0%, 52.9%, 35.6%, 27.3% and 20.0%, respectively; the positive rates of CA19-9 protein expression were 44.0%, 33.3%, 16.5%, 9.2% and 6.2%, respectively; the positive rates of CEA protein expression were 74.6%, 60.8%, 23.3%, 23.7% and 16.2%, respectively. The positive rates of the combined expression of the three biomarkers were 84.3%, 76.5%, 47.6%, 42.9% and 27.5%, respectively. In the receiver operating characteristic curves of the combination of the three biomarkers, the specificity was 88.8% for the normal controls, and the sensitivity was 58.2% for invasive cancer, 25.5% for HGD, 11.2% for LGD, and 6.5% for BCH. CONCLUSION p53, CEA and CA19-9 protein expression was correlated with esophageal carcinogenesis, and testing for the combination of these biomarkers is useful for identifying high-risk patients with precancerous lesions. PMID:27818592

  6. Ability of transplanted cultured epithelium to respond to dermal papillae.

    PubMed

    Xing, L; Kobayashi, K

    2001-10-01

    Cultured epithelium has been used successfully in the treatment of extensive burns. Regenerated epidermis, however, lacks such as hair follicles and sweat glands that are common in mammalian skin. We attempted to determine whether cultured epithelium could be induced to form hair follicles by dermal papillae, which are most important for the morphogenesis and growth of hair follicles. We cultivated adult rat sole keratinocytes, obtained the cultured epithelium, and prepared recombinants consisting of cultured epithelium and fresh dermal papillae with or without the sole dermis. These recombinants were then transplanted underneath the dermis of the dorsal skin of syngeneic rats or athymic mice. Histologic examination revealed that the transplanted cultured epithelium formed the follicular structures with sebaceous gland-like structure following induction of the dermal papillae, especially when supported by the dermis. We concluded that transplanted cultured epithelium of adult rat sole keratinocytes can respond to growth signals from adult dermal papillae.

  7. Histomorphological and Immunophenotypic Features of Pill-Induced Esophagitis

    PubMed Central

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

    2015-01-01

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

  8. Human papillomavirus-related esophageal cancer survival

    PubMed Central

    Guo, Lanwei; Liu, Shuzheng; Zhang, Shaokai; Chen, Qiong; Zhang, Meng; Quan, Peiliang; Sun, Xi-Bin

    2016-01-01

    Abstract Background: Human papillomavirus (HPV) has been identified to be related to progression of esophageal cancer. However, the results remain controversial. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Methods: The electronic databases of MEDLINE and Excerpta Medica database were searched till April 30, 2016. Study-specific risk estimates were pooled using a random-effects model. Results: Ten studies involving a total of 1184 esophageal cancer cases were included in this meta-analysis. The pooled hazard ratio comparing HPV-positive to HPV-negative esophageal cancers was 1.03 (95% confidence interval 0.78–1.37), which was not significantly correlated with improved survival. However, HPV-16-positive patients might have a significantly favorable survival (hazard ratio 0.73, 95% confidence interval 0.44–1.21). Conclusion: The meta-analysis indicated that HPV infection may not be of prognostic utility in the evaluation of factors contributing to esophageal cancer. Further large prospective studies are encouraged to stratify survival analysis by HPV type. PMID:27861358

  9. Herpes simplex esophagitis in immunocompetent hosts.

    PubMed

    Eymard, D; Martin, L; Doummar, G; Piché, J

    1997-11-01

    Over four months, three cases of biopsy-proven herpes simplex esophagitis were seen at Centre hospitalier Pierre-Boucher, Longueuil, in young adult males with no evidence of immunosuppression and negative serological testing for antibody against the human immunodeficiency virus. Clinical presentation consisted of odynophagia, fever and retrosternal chest pain. All patients rapidly improved with acyclovir therapy.

  10. Herpes simplex esophagitis in immunocompetent hosts

    PubMed Central

    Eymard, Daniel; Martin, Luc; Doummar, Gilbert; Piché, Jean

    1997-01-01

    Over four months, three cases of biopsy-proven herpes simplex esophagitis were seen at Centre hospitalier Pierre-Boucher, Longueuil, in young adult males with no evidence of immunosuppression and negative serological testing for antibody against the human immunodeficiency virus. Clinical presentation consisted of odynophagia, fever and retrosternal chest pain. All patients rapidly improved with acyclovir therapy. PMID:22346532

  11. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal stethoscope. 868.1910 Section 868.1910 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... enable the user to listen to heart and breath sounds. (b) Classification. Class I (general controls)....

  12. 21 CFR 868.1910 - Esophageal stethoscope.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 F