Johannes Lenglinger

Gastric emptying: a contributory factor in gastro-oesophageal reflux activity?

AIMS To evaluate the impact of total and proximal stomach emptying on 24 hour and postprandial reflux as well as the number of reflux episodes per hour in relation to the impact of lower oesophageal sphincter (LOS) pressure, and oesophageal contractile and clearance function. METHODS Seventy one outpatients (37 female, 34 male; age 23–82 years) with symptoms suggestive of both delayed gastric emptying and reflux referred for further investigations participated in the study. Gastric emptying of a semisolid 1168 kJ meal and oesophageal clearance of a water bolus (supine) were recorded scintigraphically, reflux by 24 hour pH monitoring, and oesophageal motility manometrically. RESULTS Slow proximal but not slow distal or total stomach emptying correlated with increased 24 hour and postprandial acid exposure and increased number of reflux episodes/hour. No relationship was found between total or proximal emptying and LOS resting pressure, oesophageal contraction amplitude, percentage of failed contractions, or clearance. Multiple linear regression analyses showed that slow proximal emptying and low LOS pressure contributed significantly to both 24 hour (p=0.0007 and p=0.0001) and two hour postprandial acid exposure (p=0.007 and p=0.0001). In contrast, the rate of total emptying contributed to neither 24 hour nor postprandial acid exposure. CONCLUSION Our data suggest that in contrast with total stomach emptying, the rate of proximal stomach emptying contributes to the extent of 24 hour as well as postprandial acid exposure and the number of reflux episodes/hour.

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.

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.

Gastric emptying of glucose solution and associated plasma concentrations of GLP-1, GIP, and PYY before and after fundoplication

BackgroundThis study was designed to assess the relationship between gastric emptying of glucose solution and the ensuing plasma concentrations of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) in patients having undergone fundoplication for gastroesophageal reflux (GERD).Subjects and methodsIn 10 male patients the emptying of 50% glucose solution was determined scintigraphically and its relationship with plasma glucose, GLP-1, PYY, and GIP concentrations was studied before and 3 months after fundoplication.ResultsIn the first 30 min after glucose ingestion, emptying was significantly (p = 0.048) faster after fundoplication than before. Emptying and GLP-1 and GIP correlated: the faster the emptying during the first 30 min the greater the concentrations integrated over that period (p = 0.04; p = 0.01; p = 0.02). Emptying and PYY concentrations were unrelated. In the 120–180 min. period, blood glucose concentrations were lower the faster the emptying in the initial 30 min (p = 0.06) and the entire 50-min recording period (p = 0.03) had been. The GLP-1 concentrations integrated over the first 30 min correlated inversely with the integrated plasma glucose during the third hour after ingestion (p = 0.004).ConclusionsAfter fundoplication, gastric emptying may, if accelerated in its initial phases, give rise to greater and earlier increases in plasma glucose, GLP-1, and GIP concentrations and thus to reactive hypoglycemia.

Upper esophageal sphincter dysfunction: diverticula–globus pharyngeus

The following discussion of upper esophageal sphincter dysfunction includes commentaries on the role of the cricopharyngeus muscle in reflux disease; the etiology and treatment of Zenker diverticulum; the use of videofluoroscopy in patients with dysphagia, suspicion of aspiration, or globus; the role of pH–impedance monitoring in globus evaluation; and treatment for reflux‐associated globus.

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.

Testing for gastroesophageal reflux in the 21st century.

The following on testing for gastroesophageal reflux in the 21st century contains commentaries on wireless pH monitoring; extension of pH recording duration to 48 or 96 h; extraesophageal GERD syndromes, diagnosis paradigms, and related investigating tools; off‐ or on‐PPI reflux monitoring in the preoperative setting; and the potential influence of PPIs on reflux parameters.

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.

Waist to hip ratio is a better predictor of esophageal acid exposure than body mass index

Obesity and gastroesophageal reflux disease (GERD) are major health problems showing an inconstant relationship in the literature. Therefore, anthropometric parameters which are predictive and can simply be assessed at first patient presentation may lead to a better patient selection for ambulatory reflux monitoring. We aimed to examine the association of body mass index (BMI) and waist to hip ratio (WHR) with gastroesophageal reflux activity during 24 hour‐pH‐impedance monitoring.

Radiofrequency ablation if Barrett's esophagus persists after fundoplication?

Dear Editor, With interest we read the article by Ciovica et al. [1], entitled ‘‘The use of medication after laparoscopic antireflux surgery,’’ which has been published in the recent issue of Surgical Endoscopy. The paper comes from a group of surgeons with large experience in antireflux surgery. In addition to their excellent surgical performance, the group elaborated an interdisciplinary approach toward gastroesophageal reflux disease (GERD) with meticulous patient workup, including high-quality endoscopy, esophageal function test, reflux monitoring, psychological support of patients, quality of life assessment [2] and life style education of patients [1]. One year after fundoplication, typical and atypical symptoms were absent in 95–100% of patients, 98% were off proton pump inhibitor (PPI) therapy, manometric characteristics of the lower esophageal sphincter and esophageal acid exposure normalized, and life quality significantly improved [1, 2]. Thus, the ‘‘Krems-antireflux program’’ seems to be very successful and is in keeping with the results of previously published series [3]. In addition, the data by Ciovica et al. [1] are of major oncological impact. Before the operation, 26.4% of patients had Barrett’s esophagus. This is cardiac mucosa with goblet cells [4] and means an increased risk for the development of esophageal adenocarcinoma (0.5% annual risk). As shown by Ciovica et al. [1], antireflux surgery worked by increasing the abdominal length of the lower esophageal sphincter by approximately 1 cm, which lead to normalization of esophageal acid exposure. Recent studies showed that effective fundoplication, i.e., pH monitoring proven control of reflux, will eliminate the risk for progression toward dysplasia and cancer [5]. In contrast, Barrett’s occurs after ineffective fundoplication with persistence of reflux [6]. Thus, it can be assumed that if the 1-year data continue to hold, the cancer risk of patients with Barrett’s esophagus will be reduced. If cancer develops after ‘‘effective’’ fundoplication, it may be due to an irreparable genetic switch that has already taken place before the operation [4]. Radiofrequency ablation represents a novel, highly effective, and promising approach for elimination of Barrett’s mucosa without and with dysplasia [7]. The method is conducted endoscopically and does not interfere with esophageal function. Thus, after fundoplication, patients will undergo surveillance endoscopies with biopsy sampling. If Barrett’s esophagus persists, ablation may be conducted to eliminate the cancer risk of these patients [7]. At that point, the multidisciplinary approach will presumably become highly effective to prevent esophageal adenocarcinoma. The authors are kindly asked to comment on our considerations.