Zusammenfassung
Das Zollinger-Ellison-Syndrom (ZES) ist pathophysiologisch durch eine Hypergastrinämie charakterisiert, die von einem Gastrin-sezernierenden neuroendokrinen Tumor mit Primärlokalisation im Duodenum oder Pankreas stammt resultiert. Die chronische Hypergastrinämie führt zu einer Säurehypersekretion und konsekutiv zu rezidivierenden oder refraktären Ulcera im oberen Gastrointestinaltrakt oder zu einer chronischen Diarrhoe. Die Hälfte aller Patienten mit ZES hat Fernmetastasen in der Leber zum Zeitpunkt der Diagnose und ebenfalls die Hälfte aller Patienten mit ZES hat als Leitsymptom der Erkrankung eine chronische Durchfallerkrankung und kein peptisches Ulkusleiden. Gastrinome manifestieren sich sporadisch oder vor dem genetischen Hintergrund des MEN-I-Syndroms. Die Diagnose basiert im wesentlichen auf der Anamnese, die Aufschluss gibt über rezidivierenden Ulkusepisoden oder schwere Refluxösophagitiden, die auf Standardtherapieregime keine Besserung erfahren, und/oder über eine chronische Diarrhoe. Die Endoskopie des oberen Gastrointestinaltraktes sichert die Diagnose des peptischen Ulkusleidens unter anderem auch in anatomischen Regionen weit distal des Bulbus duodeni oder gar im Jejunum. Ulcerationen, die gruppiert auftreten, sind häufig zu beobachten und somit verdächtig auf eine substantielle Hypersekretion von Säure. Ein pH-Wert des Magensekretes von > 2 schließt ein ZES mit sehr großer Wahrscheinlichkeit aus. Der biochemische Tumornachweis gelingt über erhöhte Serumgastrinspiegel. Der Serumgastrinspiegel kann im Nüchternzustand oder nach Stimulation mit Calcium oder Sekretin bestimmt werden. Eine sehr hohe Sensitivität für die Diagnose hat die Bestimmung des Verhältnisses der basalen (basal acid output, BAO) zur maximal stimulierten (maximal acid otuput, MAO) Säuresekretion des Magens. Ein Verhältnis von BAO / MAO von > 0,6 ist hochgradig spezifisch für ein Gastrinom. Für die Lokalisationsdiagnostik stehen neben der Computertomographie die Somatostatin-Rezeptor-Szintigraphie, der transabdominelle und der endoskopische Ultraschall zur Verfügung. Falls diese Techniken keine exakte präoperative Lokalisationsdiagnostik gestehen, besteht die Möglichkeit zum intraoperativen Ultraschall und zur Diaphanoskopie der Duodenalwand. Die Wahl der Therapie ist individuell und abhängig von der klinischen Beschwerdesymptomatik und der Tumorlokalisation. Die vollständige chirurgische Resektion bietet die einzige Chance auf eine dauerhafte Heilung des Patienten. Ist dies jedoch nicht möglich, steht das effektive pharmakologische Management des Säurehypersekretionssyndroms im Vordergrund.
Summary
The Zollinger-Ellison syndrome is characterized pathophysiologically by a significant hypergastrinemia derived from a gastrin-secreting neuroendocrine tumor with a primary location in the pancreas or duodenum. Chronic hypergastrinemia in turn triggers gastric acid hypersecretion yielding in chronic or recurrent or refractory peptic ulcer disease and/or chronic diarrhea. One half of patients with ZES will have distant metastases in the liver by the time the diagnosis is established and one half of all patients with ZES will experience chronic diarrhea as chief complaint rather than peptic ulcer-related symptoms and signs. Gastrinomas have been reported to either manifest sporadically or to occur in conjunction with the genetic backgroung of the MEN-I syndrome. Diagnosis is based on the patients history which is typically characterized by recurrent episodes of peptic ulcer disease or by severe reflux esophagitis and/or diarrhea or by acid-related symptoms which fail to respond to standard treatment regimens. Upper gastrointestinal tract endoscopy will provide evidence for peptic ulcer disease in anatomical regions located aborally the duodenal bulb within the descending part of the duodenum or even farther distally within the jejunum. Peptic ulcers frequently occur in groups indicating some substantial acid hypersecretion. A gastric pH > 2 is mutually exclusive for ZES. Increased serum gastrin levels confirm the diagnosis biochemically. Gastrin secretion can be determined in the basal state or following stimulation with secretin or calcium. High sensitivity and specifity for the diagnosis of ZES is provided by determining the ratio of basal versus pentagastrin-stimulated gastric acid secretion: The ratio of BAO / MAO > 0.6 is highly specific for gastrinoma. To localize the gastrinsecreting tumor computer-assisted tomography, endoscopic ultrasound, and somatostatin receptor scintigraphy provide useful help but most recently, endoscopic ultrasound with high resolution transducers appear to improve preoperative site localization. If modern imaging techniques fail to elucidate the site of the tumor, intraoperative diaphany may help to detect gastrinomas within the duodenal wall. Definitive treatment will only be achieved by total surgical resection of the gastrin-producing tumor in the pancreas or duodenum including dissection of the regional lymph nodes. Control of symptoms will have to be achieved by administration of highly potent proton pump inhibitors in up to 2-3-fold increased standard doses to inhibit gastric acid hypersecretion. Elevation of gastric pH > 4 will be the therapeutic target to protect the mucosa of the upper gastrointestinal tract. Basal acid output should be reduced to less than 10 mEq H+ per hour which requires administration of highly potent proton pump inhibitors with a recommended starting dose of 60 mg omeprazole equivalents per day.
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Banasch, M., Schmitz, F. Diagnosis and treatment of gastrinoma in the era of proton pump inhibitors. Wien Klin Wochenschr 119, 573–578 (2007). https://doi.org/10.1007/s00508-007-0884-2
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DOI: https://doi.org/10.1007/s00508-007-0884-2