R. Siewert

The Motor-Stimulating Effect of Natural Motilin on the Lower Esophageal Sphincter, Fundus, Antrum and Duodenum in Dogs

Natural motilin was investigated for its effect on gastrointestinal motor activity in anesthetized dogs. In doses starting from 10 ng/kg as single injection and 100 ng/kg-h as intravenous infusion, motilin induced phasic pressure changes in the lower esophageal sphincter (LES) and in the lumen of the fundus, antrum, and duodenum. Tachyphylaxis was seen in 6 out of 10 dogs. Motilin had no effect on isolated muscle strip preparations of the LES, fundus, antrum, and duodenum in this species.

Experimentelle und klinische Untersuchungen zum Wirkungsmechanismus der Fundoplicatio

SummaryApplying manometric methods a series of dog experiments was carried out in order to test and analyse the therapeutic mechanism of fundoplication. The functioning of the fundus cuff was investigated in three different models:1.the anatomically intact, sufficient lower esophageal sphincter (LES); 2. the myotomized, insufficient LES; 3. after total extirpation of the terminal esophageal muscle (circular myomectomy). The following results have been obtained: Fundoplication prevents reliably gastro-esophageal reflux. Applying fundoplication however at a sufficient sphincter with normal pressure an unphysiologically high pressure barrier is established. According to manometry in all three models, the fundus cuff builds up its own pressure zone, which is subjected to similar hormone regulations as the LES itself. The cuff has to be made of a part of the anterior fundus wall, which is the only area with a reactivity comparable to that in the LES.According to the tests performed, the therapeutic mechanism of fundoplication seems to consist of an increase in pressure, which is due to the cuff. On the basis of the higher pressure level reflux is being prevented and there is a satisfactory reactivity of the high pressure zone. In addition, mechanical factors will have to be considered. The results obtained in animal experiments have been confirmed by manometric examinations in man after fundoplication.ZusammenfassungIn einer tierexperimentellen Untersuchungsreihe an Hunden wurde der Versuch unternommen, den Wirkungsmechanismus der Fundoplicatio mit Hilfe manometrischer Untersuchungsverfahren zu analysieren. Dazu wurde die Funktion dieser Fundusmanschette an drei verschiedenen Modellen untersucht1.bei anatomisch unverändertem und suffizientem UÖS,2.bei myotomiertem und insuffizientem UÖS und3.nach totaler Exstirpation der terminalen Oesophagusmuskulatur (zirkuläre Myomektomie). Dabei konnten folgende Ergebnisse ermittelt werden: Die Fundoplicatio verhindert zuverlässig den gastrooesophagealen Reflux. Die Fundusmanschette selbst baut eine manometrisch erfaßbare eigene Druckzone auf, die ähnlichen hormonellen Regulationen unterliegt, wie der UÖS selbst. Für die Funktion dieser Manschette ist es von Wichtigkeit, daß sie aus der kardianahen Fundusvorderwand gebildet wird, da nur in diesem Bereich eine dem UÖS vergleichbare Reaktionsbereitschaft vorliegt. Der Wirkungsmechanismus der Fundoplicatio scheint nach diesen Untersuchungen darin zu liegen, daß der Sphincterdruck durch die manschettenbedingte Druckzone wieder auf ein höheres Niveau gehoben wird und so wieder Druckwerte entstehen, die den gastrooesophagealen Verschluß gewährleisten. Daneben müssen auch zusätzlich mechanische Faktoren diskutiert werden. Diese tierexperimentellen Ergebnisse finden ihre Bestätigung in den Nachuntersuchungen an mit einer Fundoplicatio versorgten Patienten.

Clinical and Manometric Investigations of the Lower Esophageal Sphincter and its Reactivity to Pentagastrin in Patients with Hiatus Hernia

After a careful clinical investigation (anamnesis, analysis of stomach secretion, X-ray tests, esophagoscopy with biopsies) of 45 patients with axial hiatus hernia and 20 healthy volunteers with no radiological signs of reflux, manometric analysis of the lower esophageal sphincter (LES) was performed. The manometric tests applied were: (1) 3-point manometry for measuring the reflexive pressure increase in the LES after abdominal compression and (2) the continuous withdrawal method before and after intravenous injection of 0.6 µg/kg pentagastrin (LES pentagastrin test). According to the results obtained by all methods applied, the patients with hiatus hernia could be divided into two groups. Group I consists of 12 patients with moderate clinical symptoms and essentially normal pressures and reactions of the LES. Group II comprises 33 patients with more severe symptomatology such as X-ray evidence of reflux (33), stenosis (3) or esophagitis of the lower esophagus (17), hyperacidity of the stomach (5), insufficient reaction of the LES to abdominal compression (29), reduced maximum pressure in the LES and an abnormally low response of the LES to intravenous pentagastrin (19). Essentially by means of the results of the LES pentagastrin test, group II could by subdivided into group IIA, with a normal, and group IIB with significantly reduced pentagastrin response. There was a good correlation between the reduced pentagastrin response and the exhibition of more severe symptoms of the other parameters tested. Thus, it could be shown that the LES-pentagastrin test could contribute to a further differentiation, which is important in respect to the therapeutic consequences and assist in a better understanding of the pathophysiological basis of the disease.

Effect of Cimetidine on Lower Esophageal Sphincter Pressure, Intragastric pH and Serum Levels of Immunoreactive Gastrin in Man

The influence of cimetidine on the lower esophageal sphincter, the intragastric pH and the serum levels of immunoreactive gastrin was investigated in eight volunteers and compared with a control group. After oral application of 400 mg cimetidine, the intragastric pH rose from 1.7 +/- 0.13 to 6.2 +/- 0.4 and the lower esophageal sphincter pressure increased slightly but significantly from 15.6 +/- 1.1 to 22.7 +/- 1.8 mm Hg after 20 min and to 25.8 +/- 2.0 after 30 min, respectively. At the same time the serum immunoreactive gastrin levels did not change. A direct effect of cimetinidine on the lower esophageal sphincter or an indirect effect via gastric alkalinization is discussed.

Klinische Ergebnisse der Fundoplicatio

SummaryA series of 50 patients was studied by esophageal manometry and X-ray prior to fundoplication and for a three month thereafter. In 49 patients a functionally intact gastroesophageal junction was documented; in one patient disintegration of the plication occured. The resting pressure of the lower esophageal sphincter was found preoperatively in the range of 10,4 ± 3,7 mm Hg; postoperative values increased to 19,0 ± 6,9 mm Hg. 10 % of patients complained postoperatively of temporary dysphagia. Only in a single instance continued dysphagia had to be treated. Inadvertently two patients were vagotomized during the operation. The data are discussed in relevance to the technical details of the operative procedure.ZusammenfassungZur Überprüfung der klinischen Ergebnisse der Fundoplicatio wurde eine Serie von 50 Patienten nach exakter Dokumentation der präoperativen Befunde manometrisch und röntgenologisch 3 Monate postoperativ nachuntersucht. Bei 49 Patienten konnte ein funktionsfähiger gastrooesophagealer Verschluß aufgezeigt werden; in einem Fall hatte sich die Fundusmanschette gelöst. Die präoperativ deutlich erniedrigten Ruhedrucke im unteren Oesophagussphincter (10,4 ± 3,7 mm Hg) konnten durch die Operation auf 19,0 ± 6,9 mm Hg angehoben werden. In 10% der Fälle bestanden unmittelbar postoperativ passagere Dysphagien, die sich in der Regel rasch zurückbildeten. Nur bei einem Patienten mußte eine persistierende Dysphagie behandelt werden. Zwei weitere Patienten waren intraoperativ unbeabsichtigt vagotomiert worden. Diese Ergebnisse werden im Hinblick auf ihre operativtechnischen Konsequenzen diskutiert.

The Relationship between Serum IRG Levels and LES Pressure under Various Conditions

In investigations with various groups of patients there was no correlation between fasting serum IRG levels and LES pressures in individual subjects with undisturbed for disturbed sphincters. After food ingestion a short phase of LES pressure increase (from 13.5 +/- 1.5 to 21.7 +/- 3.8 mm Hg) could be observed. This peak occurs during the phase of rise in gastrin level, but there was no correlation between IRG levels and LES pressure in individual cases. In patients with gastroesophageal reflux we can demonstrate a diminished release of gastrin after a test meal, but there was also a diminished capacity of the LES. In conclusion, in this investigation it has not been possible to show a clear connection in humans between serum IRG and LES function.

Klinische Ergebnisse der Oesophago-Jejunoplicatio

SummaryIndications, surgical technique, and clinical results in esophagojejunoplication are shown. In 46 patients the indication for total gastrectomy in 20 cases was a benign disease and in 26 cases cancer of the stomach. An essential feature of this method is the construction of a jejunal cuff, which is drawn around the anastomosis and the terminal esophagus. Particular advantage is the security of the anastomosis; we have observed only three leakages and these were without complications (6.5 %). The fatality rate was 8.5 %, and the total rate of complications was 26.1 %.With 30 surviving patients a postoperative follow-up was carried out, the results of which are shown. Jejunoesophageal reflux occurred in only 7.9% of these patients.ZusammenfassungDargestellt werden Indikation, operative Technik und klinische Ergebnisse der Oesophago-Jejunoplicatio.Bei 46 an derChirurgischen Universitätsklinik Göttingen operierten Patienten gab 20mal eine gutartige Grundkrankheit und 26mal ein Magencarcinom die Indikation zur totalen Gastrektomie ab. Wesen der Operationsmethode ist die Bildung einer Jejunummanschette, die um die Anastomose und terminalen Oesophagus gelegt wird. Besonderer Vorteil ist die Anastomosensicherheit; es wurden nur 3 blande verlaufende Insuffizienzen beobachtet (6,5 %). Die Operationsletalität betrug 8,5 %, die Gesamtrate an Komplikationen 26,1%. Bei 30 überlebenden Patienten konnte eine Nachuntersuchung durchgeführt werden, deren Ergebnisse vorgelegt werden. Nur in 7,9% dieser Patienten konnte ein jejunooesophagealer Reflux nachgewiesen werden.Indications, surgical technique, and clinical results in esophagojejunoplication are shown. In 46 patients the indication for total gastrectomy in 20 cases was a benign disease and in 26 cases cancer of the stomach. An essential feature of this method is the construction of a jejunal cuff, which is drawn around the anastomosis and the terminal esophagus. Particular advantage is the security of the anastomosis; we have observed only three leakages and these were without complications (6.5%). The fatality rate was 8.5%, and the total rate of complications was 26.1%. With 30 surviving patients a postoperative follow-up was carried out, the results of which are shown. Jejunoesophageal reflux occurred in only 7.9% of these patients.

24. Chirurgische Aspekte nach Resektionen an Magen und Oesophagus

SummaryResection of digestive sphincters like the pylorus (antrum) or the cardia (terminal esophagus) means reflux. Reflux is, however, not to be confused with reflux disease. Only pathologically prolonged contact of regurgitation with mucosa provides presupposition of reflux symptoms. Bilious vomit and epigastric pain are clinical symptoms of gastral reflux disease; the morphological consequence is erythemia of the stomach. Whether gastritis is also a result of reflux must remain undecided at present. The proven surgical therapy of gastral reflux disease is the Roux-en-Y operation. Esophageal reflux consequences after total gastrectomy and cardia resection are of great clinical importance. Their prophylaxis should be a deciding factor for the method chosen.ZusammenfassungDie Resektion intestinaler Schleusensysteme (Pylorus - Antrum; Kardia - terminaler Oesophagus) bedeutet Reflux. Reflux ist aber nicht gleich Refluxkrankheit zu setzen. Nur ein pathologisch verlangerter Kontakt zwischen Regurgitat and Schleimhaut schafft die Voraussetzung fur die Entstehung von Refluxfolgen. Galleerbrechen and epigastrischer Schmerz sind klinische Symptome der gastralen Refluxkrankheit, das Magenerythem morphologische Folge. Ob auch die Gastritis Refluxfolge ist, muB z. Z. noch offen bleiben. Belegte chirurgische Therapie der gastralen Refluxkrankheit ist die Roux-Y-Ableitung des Duodenalinhaltes. Oesophageale Refluxfolgen sind nach totaler Gastrektomie and nach Kardiaresektion von groBer klinischer Bedeutung. Ihre Prophylaxe sollte Gegenstand der Verfahrenswahl scin.

Kardiafunktion nach proximal-gastrischer Vagotomie

SummaryIn 36 patients with chronic duodenal ulcer disease LES-function before and after proximal-gastric vagotomy was examined manometrically and by determining pH-values in a prospective study. In addition, esophagus biopsies were taken 5 cm proximal of the cardia. 12 healthy volunteers served as controls. A direct effect of proximal-gastric vagotomy on LES-function could not be shown. On the contrary, in 38,9 % of the patients examined, preoperatively proven esophagitis disappears nearly completely 12 months following proximal gastric vagotomy. This positive effect of vagotomy is to be interpreted as a beneficial effect on regurgitated intestinal juice, more so than an effect on cardia function itself.ZusammenfassungIn einer prospektiven Studie wurde an 36 Patienten mit chronisch-rezidivierenden Ulcera duodeni die Kardiafunktion vor und nach proximal-gastrischer Vagotomie manometrisch und pH-metrisch untersucht. Zusätzlich wurden 5 cm oral der Kardia Oesophagusbiopsien entnommen. Als Kontrollkollektiv dienten 12 gesunde Probanden. Ein direkter Einfluß der proximal-gastrischen Vagotomie auf die Kardiafunktion ließ sich dabei nicht nachweisen. Im Gegenteil, eine bei 38,9% der untersuchten Ulcus-Patienten präoperativ nachweisbare Oesophagitis heilt 12 Monate nach proximalgastrischer Vagotomie weitgehend aus. Dieser positive Effekt der Vagotomie ist eher über eine günstige Beeinflussung des Regurgitates als über einen Effekt auf die Kardiafunktion zu deuten.

The Effect of Intravenous Infusion of Synthetic Human Gastrin-I on Lower Esophageal Sphincter (LES) Pressure in the Dog and its Relation to Gastrin Level

To demonstrate the relation between gastrin level and lower esophageal sphincter (LES) pressure, experiments with intravenous infusions of synthetic human gastrin-I (SHG-I) were performed in anaesthetized dogs. The results show that infusions with 5 mug-kg-1-h-1 SHG-I have an initially increasing effect on LES pressure but produce unphysiologically high gastrin blood levels. Physiological levels of gastrin were measured only using an infusion dose of 0.5 mug-kg-1-h-1, which was below the threshold for increasing LES pressure.