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DOI: 10.1055/s-2008-1027865
© Georg Thieme Verlag KG Stuttgart · New York
Impact of Pantoprazole on Duodeno-Gastro-Esophageal Reflux (DGER)
Einfluss von Pantoprazol auf den duodenogastro-ösophagealen Reflux (DGER)Publication History
manuscript received: 5.6.2008
manuscript accepted: 21.9.2008
Publication Date:
11 March 2009 (online)
![](https://www.thieme-connect.de/media/zfg/200903/lookinside/thumbnails/10.1055-s-2008-1027865-1.jpg)
Zusammenfassung
Grundlagen: Der duodenogastro-ösophageale Reflux gilt als unabhängiger Risikofaktor für einen komplizierten Verlauf einer Refluxerkrankung (GERD). Patienten mit einem Barrett-Ösophagus leiden signifikant häufiger an einem pathologischen DGER im Vergleich zu Patienten mit einem unkomplizierten Verlauf der Erkrankung. Jedoch stehen keine allgemeinen Leitlinien zur Behandlung eines DGER zur Verfügung. Methoden: 30 Patienten mit kombiniertem Reflux in pH-Metrie und Bilitec wurden prospektiv in die Studie eingeschlossen. Komplettiert wurde die Diagnostik mit einem standardisierten Fragebogen sowie einer Gastroskopie. Unter Therapie mit Pantoprazol 80 mg/d für 6 – 8 Wochen wurden pH-Metrie und Bilitec wiederholt und die klinische Symptomatik re-evaluiert. Ergebnisse: Unter Therapie mit Pantoprazol 80 mg/d konnte der saure Reflux in 28 (93 %) Patienten normalisiert werden. Gleichzeitig wurde der DGER signifikant von 19,6 % (± 13,7) auf 5,7 % (± 7,7, p < 0,05) reduziert. 15 Patienten (50 %) wiesen unter Therapie einen persistierenden DGER auf (DGER-NR-Gruppe), wobei in 15 Fällen (50 %) eine Normalisierung erreicht werden konnte (DGER-R-Gruppe). Die DGER-NR-Gruppe hatte einen signifikant ausgeprägteren DGER vor Therapie im Vergleich zu der DGER-R-Gruppe: 22,9 vs. 15,6 %. Der durchschnittliche Lebensqualitätsindex stieg von 4,78 (± 0,86) auf 8,04 (± 1,84) unter Therapie. Jedoch war ein persistierender DGER assoziiert mit einem geringeren klinischen Ansprechen. Vor allem Sodbrennen und nächtlicher Husten blieben in der DGER-NR-Gruppe bestehen. Schlussfolgerungen: Unsere Daten bestätigen, dass eine hoch dosierte Therapie mit Pantoprazol effektiv die saure Komponente eines kombinierten Refluxes reduziert. Jedoch kann eine Normalisierung des DGER lediglich in 50 % der Patienten erreicht werden. Ein ausgeprägter DGER vor Therapie verstärkt das Risiko eines persistierenden DGER unter Therapie und ist assoziiert mit einem schlechteren klinischen Ansprechen.
Abstract
Background: Duodeno-gastro-esophageal reflux (DGER) is considered as an independent risk factor for complicated reflux disease (GERD). Patients with Barrett’s esophagus have significantly higher levels of DGER than patients with uncomplicated GERD. However, the clinical response to conventional high-dose PPI therapy in patients with uncomplicated GERD and DGER is largely unknown. Methods: 30 patients with uncomplicated GERD and combined pathological reflux (acid and bile) were enrolled in the study. Clinical work-up included evaluation of clinical symptoms, esophageal manometry and upper endoscopy. After 6 – 8 weeks of treatment with Pantoprazole 80 mg/d pH measurement and Bilitec 2000 were repeated, and the pattern of symptoms was re-evaluated. Results: Under treatment with Pantoprazole 80 mg/d acid reflux was normalised in 28 patients (93 %). Similarly the mean percentage of DGER (time with an absorption greater than 0.14) was significantly reduced from 19.6 % (± 13.7) to 5.7 % (± 7.7, p < 0.05). In 15 patients (50 %) an elevated DGER persisted under treatment with Pantoprazole (DGER-NR group) whereas in 15 cases (50 %) a normalisation could be achieved (DGER-R group). The DGER-NR group had significantly higher levels of bile reflux before (and under) treatment compared to the DGER-R group: 22.9 % (9.98 %) vs. 15.6 % (0.72 %), respectively. Overall, the median quality of life index (QLI) improved from 4.78 (± 0.86) before to 8.04 ± 1.84) under therapy. The clinical response under treatment was marikedly reduced in the DGER-NR group compared to the DGER-R group: QLI 7.3 vs. 8.9. Particularly heartburn and nocturnal coughing persisted. Conclusions: Our data confirm that high-dose pantoprazole therapy effectively exerts acid suppression in GERD patients with combined pathological reflux. However, DGER could only normalised in 50 % of patients. High levels of DGER at diagnosis enhance the risk of persistent DGER under PPI therapy and are associated with a reduced clinical outcome.
Schlüsselwörter
Refluxerkrankung - GERD - Bilitec - DGER - Sodbrennen
Key words
reflux esophagitis - GERD - Bilitec - DGER - bile reflux
References
- 1 Tytgat G N, McColl K, Tack J. et al . New algorithm for the treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2008; 27 (3) 249-256
- 2 Shaker R, Castell D O, Schoenfeld P S. et al . Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Am J Gastroenterol. 2003; 98 (7) 1487-1493
- 3 Ofman J J. The economic and quality-of-life impact of symptomatic gastroesophageal reflux disease. Am J Gastroenterol. 2003; 98 (Suppl 3) S8-S14
- 4 Castell D O, Murray J A, Tutuian R. et al . Review article: the pathophysiology of gastro-oesophageal reflux disease – oesophageal manifestations. Aliment Pharmacol Ther. 2004; (Suppl 20) 914-925
- 5 Richter J E. The many manifestations of gastroesophageal reflux disease: presentation, evaluation, and treatment. Gastroenterol Clin North Am. 2007; 36 (3) 577-5ix
- 6 Pinxteren van B, Numans M E, Bonis P A. et al . Short-term treatment with proton pump inhibitors, H 2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev. 2004; 4 CD002095
- 7 Moayyedi P, Talley N J. Gastro-oesophageal reflux disease. Lancet. 2006; 367 (9528) 2086-2100
- 8 Sital R R, Kusters J G, De Rooij F W. et al . Bile acids and Barrett’s oesophagus: a sine qua non or coincidence?. Scand J Gastroenterol Suppl (243). 2006; 243 11-17
- 9 Tack J. Review article: the role of bile and pepsin in the pathophysiology and treatment of gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006; 24 (Suppl) 210-216
- 10 Koek G H, Vos R, Sifrim D. et al . Mechanisms underlying duodeno-gastric reflux in man. Neurogastroenterol Motil. 2005; 17 (2) 191-199
- 11 Stipa F, Stein H J, Feussner H. et al . Assessment of non-acid esophageal reflux: comparison between long-term reflux aspiration test and fiberoptic bilirubin monitoring. Dis Esophagus. 1997; 10 (1) 24-28
- 12 Vaezi M F, Lacamera R G, Richter J E. Validation studies of Bilitec 2000: an ambulatory duodenogastric reflux monitoring system. Am J Physiol. 1994; 267 G1050-G1057
- 13 Hirota W K, Loughney T M, Lazas D J. et al . Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction: prevalence and clinical data. Gastroenterology. 1999; 116 (2) 277-285
- 14 Vaezi M F, Richter J E. Synergism of acid and duodenogastroesophageal reflux in complicated Barrett’s esophagus. Surgery. 1995; 117 (6) 699-704
- 15 Koop H, Schepp W, Muller-Lissner S. et al . Consensus conference of the DGVS on gastroesophageal reflux. Z Gastroenterol. 2005; 43 (2) 163-164
- 16 Kunsch S, Linhart T, Fensterer H. et al . Prevalence of a Pathological DGER (Duodeno-Gastric-Oesophageal Reflux) in Patients with Clinical Symptoms of Reflux Disease. Z Gastroenterol. 2008; 46 (5) 409-414
- 17 Richter J E. Duodenogastric Reflux-induced (Alkaline) Esophagitis. Curr Treat Options Gastroenterol. 2004; 7 (1) 53-58
- 18 Menges M, Muller M, Zeitz M. Increased acid and bile reflux in Barrett’s esophagus compared to reflux esophagitis, and effect of proton pump inhibitor therapy. Am J Gastroenterol. 2001; 96 (2) 331-337
- 19 Marshall R E, Anggiansah A, Manifold D K. et al . Effect of omeprazole 20 mg twice daily on duodenogastric and gastro-oesophageal bile reflux in Barrett’s oesophagus. Gut. 1998; 43 (5) 603-606
- 20 Miwa K, Sahara H, Segawa M. et al . Reflux of duodenal or gastro-duodenal contents induces esophageal carcinoma in rats. Int J Cancer. 1996; 67 (2) 269-274
- 21 Orlando R C, Bozymski E M. Heartburn in pernicious anemia – a consequence of bile reflux. N Engl J Med. 1973; 289 (10) 522-523
- 22 Wilmer A, Tack J, Frans E. et al . Duodenogastroesophageal reflux and esophageal mucosal injury in mechanically ventilated patients. Gastroenterology. 1999; 116 (6) 1293-1299
- 23 Schweitzer E J, Bass B L, Batzri S. et al . Bile acid accumulation by rabbit esophageal mucosa. Dig Dis Sci. 1986; 31 (10) 1105-1113
- 24 Tselepis C, Morris C D, Wakelin D. et al . Upregulation of the oncogene c-myc in Barrett’s adenocarcinoma: induction of c-myc by acidified bile acid in vitro. Gut. 2003; 52 (2) 174-180
- 25 Zhang F, Altorki N K, Wu Y C. et al . Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids. Gastroenterology. 2001; 121 (6) 1391-1399
- 26 Vaezi M F, Richter J E. Synergism of acid and duodenogastroesophageal reflux in complicated Barrett’s esophagus. Surgery. 1995; 117 (6) 699-704
- 27 Koek G H, Tack J, Sifrim D. et al . The role of acid and duodenal gastroesophageal reflux in symptomatic GERD. Am J Gastroenterol. 2001; 96 (7) 2033-2040
- 28 Tack J, Koek G, Demedts I. et al . Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barrett’s esophagus: acid reflux, bile reflux, or both?. Am J Gastroenterol. 2004; 99 (6) 981-988
- 29 Castell D O, Vela M. Combined multichannel intraluminal impedance and pH-metry: an evolving technique to measure type and proximal extent of gastroesophageal reflux. Am J Med. 2001; 111 (Suppl 8A) 157S-159S
- 30 Weigt J, Monkemuller K, Kolfenbach S. et al . Standards and innovations in the diagnosis of gastroesophageal reflux disease. Z Gastroenterol. 2007; 45 (11) 1141-1149
- 31 Wise J L, Murray J A. Utilising multichannel intraluminal impedance for diagnosing GERD: a review. Dis Esophagus. 2007; 20 (2) 83-88
- 32 Pace F, Sangaletti O, Pallotta S. et al . Biliary reflux and non-acid reflux are two distinct phenomena: a comparison between 24-hour multichannel intraesophageal impedance and bilirubin monitoring. Scand J Gastroenterol. 2007; 42 (9) 1031-1039
- 33 Vaezi M F, Sears R, Richter J E. Placebo-controlled trial of cisapride in postgastrectomy patients with duodenogastroesophageal reflux. Dig Dis Sci. 1996; 41 (4) 754-763
- 34 Zhang Q, Lehmann A, Rigda R. et al . Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut. 2002; 50 (1) 19-24
- 35 Penagini R, Schoeman M N, Dent J. et al . Motor events underlying gastro-oesophageal reflux in ambulant patients with reflux oesophagitis. Neurogastroenterol Motil. 1996; 8 (2) 131-141
- 36 Sifrim D, Holloway R, Silny J. et al . Composition of the postprandial refluxate in patients with gastroesophageal reflux disease. Am J Gastroenterol. 2001; 96 (3) 647-655
- 37 Koek G H, Sifrim D, Lerut T. et al . Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors. Gut. 2003; 52 (10) 1397-1402
- 38 Stein H J, Kauer W K, Feussner H. et al . Bile reflux in benign and malignant Barrett’s esophagus: effect of medical acid suppression and nissen fundoplication. J Gastrointest Surg. 1998; 2 (4) 333-341
- 39 Varga G, Cseke L, Kalmar K. et al . Surgical treatment of duodeno-gastro-esophageal reflux disease: duodenal switch. Magy Seb. 2007; 60 (5) 243-247
- 40 Strignano P, Collard J M, Michel J M. et al . Duodenal switch operation for pathologic transpyloric duodenogastric reflux. Ann Surg. 2007; 245 (2) 247-253
Dr. Steffen Kunsch
Klinik für Innere MedizinGastroenterologie, Endokrinologie und StoffwechselUniversitätsklinikum Gießen und Marburg, Standort Marburg
Baldingerstraße
35039 Marburg
Germany
Email: kunsch@med.uni-marburg.de