Enrico P. Cosentini

Effects of substance P on human colonic mucosa in vitro.

Previous studies indicated that the peptide substance P (SP) causes Cl--dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10-8 to 10-6 M) induced a rapid, monophasic concentration and Cl--dependent, bumetanide-sensitive short-circuit current ( I sc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1(SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced I sc increase without impairing forskolin- and carbachol-mediated I sc increase. We conclude that SP stimulates Cl--dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.Previous studies indicated that the peptide substance P (SP) causes Cl--dependent secretion in animal colonic mucosa. We investigated the effects of SP in human colonic mucosa mounted in Ussing chamber. Drugs for pharmacological characterization of SP-induced responses were applied 30 min before SP. Serosal, but not luminal, administration of SP (10(-8) to 10(-6) M) induced a rapid, monophasic concentration and Cl--dependent, bumetanide-sensitive short-circuit current (Isc) increase, which was inhibited by the SP neurokinin 1 (NK1)-receptor antagonist CP-96345, the neuronal blocker TTX, the mast cell stabilizer lodoxamide, the histamine 1-receptor antagonist pyrilamine, and the PG synthesis inhibitor indomethacin. SP caused TTX- and lodoxamide-sensitive histamine release from colonic mucosa. Two-photon microscopy revealed NK1 (SP)-receptor immunoreactivity on nerve cells. The tyrosine kinase inhibitor genistein concentration dependently blocked SP-induced Isc increase without impairing forskolin- and carbachol-mediated Isc increase. We conclude that SP stimulates Cl--dependent secretion in human colon by a pathway(s) involving mucosal nerves, mast cells, and the mast cell product histamine. Our results also indicate that tyrosine kinases may be involved in this SP-induced response.

Histopathology of the endoscopic esophagogastric junction in patients with gastroesophageal reflux disease.

ZusammenfassungHINTERGRUND: Unklar ist, ob der Beginn der endoskopischen Magenfalten auch dem anatomischen ösphagogastralen Übergang entspricht. Wir haben Endoskopie und Histopathologie des ösophagogastralen Übergangs bei Patienten mit gastroösophagealer Refluxkrankheit (GERD) verglichen. METHODIK: Bei 102 Personen (60 Frauen) mit GERD wurden Endoskopie und multi Level Biopsien vom Beginn der Magenfalten (= level 0), 0,5, 1,0 cm distal und 0,5, ≥ 1 cm proximal davon durchgeführt. Zylinderepithel-Ösophagus (columnar lined esophagus = CLE) wurde entsprechend der Paull Chandrasoma Klassifikation, die Ösophagitis nach der Los Angeles Klassifikation befundet. Hiatus Hernie lag vor, wenn die Magenfalten ≥ 2 cm über dem Zwerchfell-Niveau begannen, die ösophagogastrische Klappe wurde entsprechend der Hill Klassifikation beurteilt. ERGEBNISSE: Alle Personen hatten CLE, maximal am Level 0 (97%), mit nach proximal und distal abnehmender Häufigkeit (81%, 28%, 40% and 18% bei Biopsielevel −0,5, −1,0, + 0,5, bzw. + 1,0 cm). Histopathologischer CLE (= Distanz zwischen CLE positiven Biopsie Levels) war länger als endoskopischer CLE (p < 0,001). Alle 19 Personen mit intestinaler Metaplasie (18,6%) wurden durch 4-Quadranten Biopsien vom Platten-Zylinderepithel Übergang und 0,5 cm distal davon identifiziert. Jene mit intestinaler Metaplasie waren älter, hatten häufiger eine Hernie, höheren Hill Grad und endoskopisch sichtbaren CLE (p < 0,05). Kein signifikanter Unterschied zeigte sich bezüglich Geschlecht, Ösophagitis und Länge von endoskopischen und histologischem CLE (p > 0,05). Dysplasie oder Karzinom lagen nicht vor. ZUSAMMENFASSUNG: Der Übergang Ösophagus – Magen kann endoskopisch nicht erhoben werden, dies gelingt durch Histopathologie von Biopsien. Die Wahrscheinlichkeit, intestinale Metaplasie zu diagnostizieren, ist in Biopsien aus der Platten-, Zylinderepithelgrenze am höchsten.SummaryBACKGROUND: Discrepancy exists between the endoscopic (rugal folds) and the histopathologic (oxyntic mucosa) definition of proximal stomach. We compared endoscopy and histopathology of the esophagogastric junction in patients with gastroesophageal reflux disease. METHODS: A total of 102 consecutive patients (60 women) with gastroesophageal reflux disease prospectively underwent endoscopy including multilevel biopsy sampling at the level of the rise of rugal folds (level 0), and also 0.5 cm and 1.0 cm distal and 0.5 cm and ≥ 1 cm proximal to this point. Columnar lined esophagus (CLE) was cataloged according to the histopathologic Paull-Chandrasoma classification and esophagitis according to the endoscopic Los Angeles classification. Hiatal hernia was diagnosed if the endoscopic rugal folds commenced ≥ 2 cm above the diaphragm; competency of the esophagogastric valve was graded according to the Hill classification. RESULTS: All patients had histopathologic CLE with maximal presence at level 0 (97%) and a decrease towards proximal and distal biopsy levels (level −0.5 cm, 81%; level −1.0, 28%; level + 0.5 cm, 40%; level + 1.0 cm, 18%). Histopathologic CLE (distance between CLE-positive biopsy levels) was longer than endoscopic CLE (P < 0.001). All 19 patients with intestinal metaplasia (18.6%) were identified from 4-quadrant biopsies obtained at the squamocolumnar junction and at 0.5 cm distal from it. Persons with intestinal metaplasia were significantly older, had increased frequency of endoscopic hiatal hernia, higher Hill grade and presence of endoscopic CLE (P < 0.05); no significant difference was observed regarding sex, endoscopic esophagitis or length of endoscopic and histopathologic CLE (P > 0.05). None of the patients had dysplasia or carcinoma. CONCLUSIONS: In patients with gastroesophageal reflux disease the esophagogastric junction cannot be identified by endoscopy but requires histopathology of multilevel biopsies. The squamocolumnar junction harbors the highest yield of intestinal metaplasia.

Bacteroides fragilis toxin 2 damages human colonic mucosa in vitro

BACKGROUND Strains ofBacteroides fragilis producing a 20 kDa protein toxin (B fragilis toxin (BFT) or fragilysin) are associated with diarrhoea in animals and humans. Although in vitro results indicate that BFT damages intestinal epithelial cells in culture, the effects of BFT on native human colon are not known. AIMS To examine the electrophysiological and morphological effects of purified BFT-2 on human colonic mucosa in vitro. METHODS For resistance (R) measurements, colonic mucosa mounted in Ussing chambers was exposed to luminal or serosal BFT-2 (1.25–10 nM) and after four hours morphological damage was measured on haematoxylin and eosin stained sections using morphometry. F actin distribution was assessed using confocal microscopy. RESULTS Serosal BFT-2 for four hours was four-, two-, seven-, and threefold more potent than luminal BFT-2 in decreasing resistance, increasing epithelial3H-mannitol permeability, and damaging crypt and surface colonocytes, respectively (p<0.05). Confocal microscopy showed reduced colonocyte F actin staining intensity after exposure to BFT-2. CONCLUSIONS BFT-2 increases human colonic permeability and damages human colonic epithelial cells in vitro. These effects may be important in the development of diarrhoea and intestinal inflammation caused by B fragilis in vivo.

Effects of extracellular pH on intracellular pH-regulation and growth in a human colon carcinoma cell-line

Mechanisms of intracellular pH (pHi) regulation seem to be involved in cellular growth and cell division. Little is known about how extracellular acidosis, known to occur in central regions of solid tumors, or alkaline conditions affect pHi regulation in colonic tumors. pHi changes in the colonic adenocarcinoma cell-line SW-620 were recorded by spectrofluorimetric monitoring of the pH-sensitive, fluorescent dye BCECF, and proliferative activity was assessed by [3H]thymidine uptake. Resting pHi in Hepes-buffered solution was 7.53 +/- 0.01 (n = 36). Both 1 mM amiloride and Na(+)-free solution inhibited pHi recovery from acidification and decreased pHi in resting cells. In HCO3-/CO2-buffered media resting pH1 was 7.42 +/- 0.01 (n = 36). Recovery from acidification was Na(+)-dependent, CI(-)-independent, and only partially blocked by 1 mM amiloride. In the presence of amiloride and 200 microM H2DIDS pHi recovery was completely inhibited. In Na(+)-free solution pHi decreased from 7.44 +/- 0.04 to 7.29 +/- 0.03 (n = 6) and no alkalinization was observed in CI(-)-free medium. Addition of 5 microM tributyltin bromide (an anion/OH-exchange ionophore) caused pHi to decrease from 7.43 +/- 0.05 to 7.17 +/- 0.08 (n = 5). The effects of pH0 on steady-state pHi, pHi recovery from acidification and proliferative activity after 48 h were investigated by changing buffer [CO2] and [HCO3-]. In general, increases in pH0 between 6.7 and 7.4 increased pHi recovery, steady-state pHi and growth rates. In summary, SW-620 cells have a resting pHi > 7.4 at 25 degrees C, which is higher than other intestinal cells. Acid extrusion in physiological bicarbonate media is accomplished by a pHi-sensitive Na+/H+ exchanger and a pHi-insensitive Na(+)-HCO3-cotransporter, both of which are operational in control cells at the resting pHi. No evidence for activity of a CI-/HCO3- exchanger was found in these cells, which could account for the high pHi observed and may explain why the cells continue to grow in acidic tumor environments.

Epidermal growth factor attenuates Clostridium difficile toxin A- and B-induced damage of human colonic mucosa

Epidermal growth factor (EGF) exhibits a cytoprotective effect on gastrointestinal epithelia via a receptor-mediated mechanism. We investigated the effect of EGF on Clostridium difficile toxin A (TxA)- and toxin B (TxB)-induced damage of human colon. Ussing-chambered colonic mucosa was exposed serosally to EGF before and during luminal exposure to TxA and TxB. Resistance was calculated from potential difference and short-circuit current. Epithelial damage was assessed by light microscopy and alteration of F-actin by fluoresceinated phalloidin. Luminal exposure of colonic strips to TxA and TxB caused a time- and dose-dependent decrease in electrical resistance, necrosis and dehiscence of colonocytes, and disruption and condensation of enterocyte F-actin. These effects were inhibited by prior, but not simultaneous, serosal application of EGF (20 nM). Administration of the tyrosine kinase inhibitor genistein (10-6 M) inhibited the protective effects of EGF. We conclude that EGF protects against TxA and TxB probably by stabilizing the cytoskeleton, the main target of these toxins.

Histopathology of columnar-lined esophagus in patients with gastroesophageal reflux disease

ZusammenfassungHINTERGRUND: Es herrscht Uneinigkeit darüber, ob ein endoskopisch normal erscheinender gastroösophagealer Übergang bei Patienten mit gastroösophagealer Refluxkrankheit biopsiert werden soll. Wir beschäftigten uns mit dieser Frage und setzten Videoendoskopie und Histopatholgie ein. METHODEN: Bei 114 aufeinander folgenden Patienten (58 männliche) mit Symptomen der gastroösophagealen Refluxkrankheit wurde die Endoskopie inklusive Biopsien aus dem gastroösophagealen Übergang prospektiv dokumentiert. Das Vorliegen einer magenartigen Schleimhaut proximal des Anstiegs der Magenfalten wurde als endoskopisch sichtbares Zylinderepithelsegment definiert. Die Histopathologie wurde entsprechend der Paull-Chandrasoma Klassifikation durchgeführt. ERGEBNISSE: 85 Patienten (74,6%) hatten ein endoskopisch sichtbares Zylinderepithelsegment mit Längen von ≤0,5 cm (n = 82), 1 cm (n = 2) und 7 cm (n = 1). 29 Patienten (25,4%) hatten eine endoskopisch normal erscheinende Schleimhautgrenze. Histopathologisch hatten alle Patienten einen Zylinderepithel-Ösophagus. Eine intestinale Metaplasie und eine niedrig-gradige Dysplasie wurden bei 26 (22,8%) bzw. bei 5 (4,4%) identifiziert. Die Häufigkeit der intestinalen Metaplasie und der Dysplasie war zwischen endoskopisch sichtbarem Zylinderepithel-Ösophagus und normalem Übergang statistisch nicht signifikant unterschiedlich (p = 0,408 bzw. p = 0,775). Das Auftreten der intestinalen Metaplasie war unabhängig von einer Ösophagitis und einer Hiatushernie (p = 0,398 bzw. p = 0,405). ZUSAMMENFASSUNG: Ein Zylinderepithel-Ösophagus kann durch die Endoskopie nicht ausgeschlossen werden. Bei Patienten mit gastrosösophagealer Refluxkrankheit werden zum histopathologischen Ausschluss einer intestinalen Metaplasie und einer niedriggradigen Dysplasie Biopsien aus einem normal erscheinenden Schleimhautübergang empfohlen.SummaryBACKGROUND AND AIMS: The question of whether an endoscopically normal-appearing esophagogastric junction should be biopsied in patients with gastroesophageal reflux disease is controversial. We have addressed this issue using endoscopy and histopathology. METHODS: A total of 114 consecutive patients (58 males) with symptoms of gastroesophageal reflux disease prospectively underwent endoscopy, including biopsy sampling from the esophagogastric junction. Endoscopically visible columnar-lined esophagus was defined by the presence of gastric-type mucosa above the level of the rise of the gastric folds. Histopathology was conducted using the Paull-Chandrasoma classification. RESULTS: Of the 114 patients, 85 (74.6%) had endoscopically visible columnar-lined esophagus of length ≤0.5 cm (n = 82), 1 cm (n = 2) and 7 cm (n = 1); 29 patients (25.4%) had a normal endoscopic junction. All patients had histopathologic columnar-lined esophagus. Intestinal metaplasia and low-grade dysplasia was identified in 26 (22.8%) and 5 (4.4%) individuals, respectively, and was not statistically different in endoscopically normal vs. abnormal junction (P = 0.408 for intestinal metaplasia, P = 0.775 for low grade dysplasia). Intestinal metaplasia was independent from endoscopic esophagitis (P = 0.398) and hiatal hernia (P = 0.405). CONCLUSIONS: Columnar-lined esophagus cannot be excluded by endoscopy. In patients with gastroesophageal reflux disease, biopsy sampling of normal-appearing junction is recommended for histopathologic exclusion of intestinal metaplasia and low-grade dysplasia.

Dynamic MR imaging of the gastroesophageal junction in healthy volunteers during bolus passage.

To evaluate the feasibility of noninvasive dynamic fast magnetic resonance imaging (MRI) during swallowing in healthy volunteers, and to determine esophageal function at the gastroesophageal junction during swallowing.

Review on novel concepts of columnar lined esophagus

SummaryBackgroundColumnar lined esophagus (CLE) is a marker for gastroesophageal reflux and associates with an increased cancer risk among those with Barrett’s esophagus. Recent studies fostered the development of integrated CLE concepts.MethodsUsing PubMed, we conducted a review of studies on novel histopathological concepts of nondysplastic CLE.ResultsTwo histopathological concepts—the squamo-oxyntic gap (SOG) and the dilated distal esophagus (DDE), currently model our novel understanding of CLE. As a consequence of reflux, SOG interposes between the squamous lined esophagus and the oxyntic mucosa of the proximal stomach. Thus the SOG describes the histopathology of CLE within the tubular esophagus and the DDE, which is known to develop at the cost of a shortened lower esophageal sphincter and foster increased acid gastric reflux. Histopathological studies of the lower end of the esophagus indicate, that the DDE is reflux damaged, dilated, gastric type folds forming esophagus and cannot be differentiated from proximal stomach by endoscopy. While the endoscopically visible squamocolumnar junction (SCJ) defines the proximal limit of the SOG, the assessment of the distal limit requires the histopathology of measured multilevel biopsies. Within the SOG, CLE types distribute along a distinct zonation with intestinal metaplasia (IM; Barrett’s esophagus) and/or cardiac mucosa (CM) at the SCJ and oxyntocardiac mucosa (OCM) within the distal portion of the SOG. The zonation follows the pH-gradient across the distal esophagus. Diagnosis of SOG and DDE includes endoscopy, histopathology of measured multi-level biopsies from the distal esophagus, function, and radiologic tests. CM and OCM do not require treatment and are surveilled in 5 year intervals, unless they associate with life quality impairing symptoms, which demand medical or surgical therapy. In the presence of an increased cancer risk profile, it is justified to consider radiofrequency ablation (RFA) of IM within clinical studies in order to prevent the progression to dysplasia and cancer. Dysplasia justifies RFA ± endoscopic resection.ConclusionsSOG and DDE represent novel concepts fusing the morphological and functional aspects of CLE. Future studies should examine the impact of SOG and DDE for monitoring and management of gastroesophageal reflux disease (GERD).ZusammenfassungHintergrundZylinderepithel-Ösophagus (engl. columnar lined esophagus; CLE) zeigt gastroösophagealen Reflux und bedingt bei jenen mit einem Barrett Ösophagus ein erhöhtes Krebsrisiko. Rezente Studien beschreiben ein integriertes morphofunktionales CLE Konzept.MethodikDiese PubMed basierte Analyse gibt eine Übersicht zu neuen histopathologischen Konzepten zu CLE ohne Dysplasie.ErgebnisseUnsere neue Vorstellung zu CLE wird anhand von zwei neuen histopathologischen Konzepten dargestellt: dem Mukosasegment zwischen Plattenepithel und oxntischer Magenschleimhaut (engl. squamo-oxntic gap; SOG) und dem dilatierten distalen Ösophagus (engl. dilated distal esophagus; DDE). Als Folge des Reflux entsteht das SOG zwischen dem von Plattenepithel ausgekleideten Ösophagus und des von oxyntischer Mukosa ausgekleideten proximalen Magens. SOG beschreibt die Histologie des CLE im tubulären Ösophagus und DDE, welcher auf Kosten des durch den Reflux verkürzten unteren Ösophagussphinkters entsteht und damit vermehrten Rückfluss des sauren Mageninhalts begünstigt. Morphologische Untersuchungen des Ausgangs der Speiseröhre zeigten, dass der DDE Reflux-geschädigter, dilatierter, magenähnliche Falten bildender Ösophagus ist und in der Endoskopie nicht vom proximalen Magen unterschieden werden kann. Während die proximale Grenze des SOG der endoskopisch definierbaren Platten-Zylinderepithelgrenze entspricht, kann die untere Grenze des SOG nur mittels Fusion von Biopsie-Lokalisation und der Histologie von aus diesem Bereich entnommenen Gewebeproben bestimmt werden. Im SOG ordnen sich die CLE Typen entsprechend einer typischen proximalen-distalen Verteilung mit intestinaler Metaplasie (IM, Barrett Ösophagus) ± Kardia Schleimhaut (CM) an der Platten-Zylinderepithelgrenze und Oxyntokardia (OCM) Mukosa im distalen Abschnitt des SOG. Die Ausrichtung folgt dem Reflux-bedingte pH Gradienten entlang des unteren Ösophagus. Die Diagnose von SOG und DDE erfolgt mittels Endoskopie, Histologie von Multi-Level Biopsien aus dem Ausgang der Speiseröhre sowie Funktionstests und Röntgenuntersuchungen. CM und OCM an sich bedürfen keiner Therapie und sollen in 5 Jahren nachuntersucht werden, nur assoziierte Reflux Beschwerden, welche die Lebensqualität beeinträchtigen, sollen medikamentös oder chirurgisch behandelt werden. Bei entsprechendem Krebsrisiko ist es gerechtfertigt, bei IM ohne Dysplasie eine Radiofrequenzablation (RFA) im Rahmen klinischer Studien zu erwägen, um damit die Entstehung von Dysplasie und Karzinom zu verhindern. Dysplasie rechtfertigt eine RFA ± endoskopischer Resektion.SchlussfolgerungenSOG und DDE sind neue Konzepte, welche Morphologie und Funktion des Zylinderepithel-Ösophagus integrieren. Die Zukunft wird zeigen, welche Bedeutung diese neuen Konzepte für Diagnose und Therapie der gastroösophagealen Refluxkrankheit haben.

Video-endoscopy for evaluation of columnar lined esophagus in patients with gastroesophageal reflux disease

ZusammenfassungGRUNDLAGEN: Angabe der Biopsielokalisation (Ösophagus vs. Magen) ist notwendig, um die histologische Diagnose von Reflux-assoziierten Veränderungen am Übergang Ösophagus/Magen zu erstellen. Wir haben den Wert der Videoendoskopie für die Diagnostik am ösophagogastralen Übergang untersucht. METHODIK: 29 konsekutive Patienten (m:w = 17:12) mit gastroösophagealer Refluxkrankheit (GERD) wurden prospektiv endoskopiert (EGD). EGD und Biopsien wurden digital aufgezeichnet und danach analysiert. Nach initialer histologischer Diagnose basierend auf dem ersten EGD-Befund erfolgte eine revidierte Diagnose basierend auf dem Befund nach EGD-Review. ERGEBNISSE: Bei 17 Patienten (59 %) stimmten revidierter und erster Befund überein (normale Junktion: n = 4; abnormale Junktion mit Zylinderepithelsegment im Ösophagus [CLE]: n = 13). Die Histologie zeigte Karditis (n = 3) und Cardia-intestinale Metaplasie (n = 1) in Patienten mit normaler Junktion; CLE (n = 8) und Ösophagusintestinale Metaplasie (EIM) (n = 5) bei abnormaler Junktion (CLE ≤ 0,5–7 cm). Bei 12 Patienten (41 %) mit CLE ≤ 0,5 cm unterschied sich die revidierte Diagnose von der Erstdiagnose (abnormale Junktion: n = 12). Die Histopathologie zeigte CLE (n = 9) und Ösophagus-intestinale Metaplasie (n = 3). Die Misinterpretation resultierte aus kurzer Dauer der Sequenzen mit unbeeinträchtigter Sicht zur EGJ (<0,001) und war unabhängig von der zirkulären Ausdehnung der CLE-Segmente (p = 0,160). EIM zeigte sich nur in cardiac, nicht aber in oxyntocardiac Mukosa. SCHLUSSFOLGERUNGEN: Bei der EGD werden Zylinderepithelsegmente im Ösophagus ≤ 0,5 cm zwar biopsiert, aber dem falschen Organ zugeordnet (Magen vs. Ösophagus) und somit Vorläuferläsionen zum Barrett Ösophagus übersehen.SummaryBACKGROUND: Information on biopsy location (esophageal vs. stomach) is required for histopathologic diagnosis of reflux associated morphologic changes at the esophagogastric junction (EGJ). We evaluated the impact of digital recording of esophagogastroduodenoscopy (EGD) on diagnosis of epithelial disorders of the EGJ. METHODS: 29 consecutive patients (male:female = 17:12) with gastroesophageal reflux disease (GERD) prospectively underwent EGD. EGD including biopsy sampling from EGJ was digitally recorded and reviewed. Initial histopathology report based on the initial EGD-report was followed by a revised histopathology report based on a revised evaluation of endoscopy recording. RESULTS: In 17 patients (59%) revised evaluation was in agreement with initial diagnosis (normal junction: n = 4; abnormal junction with columnar lined esophagus [CLE]: n = 13). Histopathology showed carditis (n = 3) and cardia intestinal metaplasia (n = 1) in patients with normal junction; CLE (n = 8) and esophagus intestinal metaplasia (EIM) (n = 5) for abnormal junctions (CLE ≤ 0.5–7 cm). In 12 patients (41%) with CLE ≤ 0.5 cm revised evaluation differed from initial reports (abnormal junction: n = 12). Histopathology showed CLE (n = 9) and esophagus intestinal metaplasia (n = 3). Misinterpretation resulted from short duration of sequences with unimpaired vision of the EGJ (<0.001) and were unaffected by circumferential extent of CLE (p = 0.160). EIM was only present within cardiac, but not within oxyntocardiac mucosa. CONCLUSIONS: During EGD, CLE-segments ≤ 0.5 cm at the EGJ are biopsy sampled but incorrectly assigned (stomach vs. esophagus) and precursor lesions of Barrett esophagus and esophageal adenocarcinoma are missed. Our data indicate that review of digital EGD recording contributes towards improving accuracy and reproducibility of diagnosis of columnar lined esophagus.

Behandlung der Achalasie

SummaryAchalasia is a condition of unknown etiology. It represents a motor disorder of the esophagus characterized by absent or incomplete relaxation of the lower esophageal sphincter upon swallowing and by nonpropulsive swallow-induced contraction waves or amotility of the esophageal body. Dysphagia and regurgitation of ingesta are the most frequent symptoms. Medical treatment, i.e. by calcium-channel blockers and nitric oxide donors, may be tried in patients with mild dysphagia or in elderly patients but rarely yields adequate symptom relief. Mechanical dilatation of the achalasic sphincter may be performed as an initial treatment option. Intrasphincteric injections of botulinum toxin seemed to be a promising alternative, but it has become obvious that, in most cases, repeated applications of the toxin are required to maintain patients symptom-free. Myotomy of the achalasic sphincter with or without fundoplication to prevent gastroesophageal reflux, is employed mainly in patients in whom dilatations have failed, but since the introduction of minimally invasive surgery, myotomy has become the primary treatment at many centers. This article aims to provide an overview of the development of the conservative and surgical treatment of achalasia.ZusammenfassungDie Achalasie ist eine Motilitätsstörung der Speiseröhre unklarer Ätiologie. Sie ist durch eine fehlende oder nur geringe Relaxation des gastroösophagealen Sphinkters während des Schluckaktes und durch zumindest zum Teil nichtpropulsive Kontraktionswellen oder eine komplette Amotilität des Ösophaguskörpers gekennzeichnet. Klinisch äußert sie sich vor allem in Dysphagie und Regurgitationen. Eine medikamentöse Therapie ist bei geringgradiger Dysphagie möglich, bei ausgeprägter Dysphagie stellt die mechanische Dilatation eine initiale Therapieoption dar. Botulinumtoxin-Injektionen in den ösophagogastrischen Übergangsbereich schienen zunächst vielversprechend, es erwies sich aber, dass die Wirkung nur kurz anhält und wiederholte Applikationen erforderlich sind. Die chirurgische Behandlung, nämlich die Myotomie mit oder ohne Antirefluxplastik, wird vor allem nach erfolglosen Dilatationen durchgeführt, seit der Einführung minimal-invasiver chirurgischer Techniken aber zunehmend als primäre Therapie angewandt. Die vorliegende Arbeit gibt einen Überblick über die Entwicklung der konservativen und chirurgischen Behandlungsmethoden.Achalasia is a condition of unknown etiology. It represents a motor disorder of the esophagus characterized by absent or incomplete relaxation of the lower esophageal sphincter upon swallowing and by non-propulsive swallow-induced contraction waves or amotility of the esophageal body. Dysphagia and regurgitation of ingesta are the most frequent symptoms. Medical treatment, i.e. by calcium-channel blockers and nitric oxide donors, may be tried in patients with mild dysphagia or in elderly patients but rarely yields adequate symptom relief. Mechanical dilatation of the achalasic sphincter may be performed as an initial treatment option. Intrasphincteric injections of botulinum toxin seemed to be a promising alternative, but it has become obvious that, in most cases, repeated applications of the toxin are required to maintain patients symptom-free. Myotomy of the achalasic sphincter with or without fundoplication to prevent gastroesophageal reflux, is employed mainly in patients in whom dilatations have failed, but since the introduction of minimally invasive surgery, myotomy has become the primary treatment at many centers. This article aims to provide an overview of the development of the conservative and surgical treatment of achalasia.