The three year results of a manufacturer sponsored randomized trial comparing laparoscopic fundoplication and esomeprazol (the Lotus study) were published recently (Lundell 2008). Following fundoplication 90 % of patients were satisfactorily freed from reflux symptoms after three years, as well as 93% of the patients on esomeprazole therapy (NS). Significantly more patients suffered from heartburn and regurgitation in the medical group, indicating a more complete symptom control after surgery (p<0.001). Dysphagia - mostly mild - was reported by around only 15% of patients after surgery - fewer than preoperatively (18%), and by 4 % in the medical group. Flatulence was encountered in more patients in the fundoplication group. Quality of life scores showed greater improvement in the surgical patients than in the medical patients for all QOLRAD (quality of life in reflux and dyspepsia) dimensions and for the reflux dimensions of the GSRS (gastrointestinal symptom rating scale) questionnaire (p<0.001). Only 3% complications occurred after fundoplication during the hospital stay or the 30 postoperative days. There was no mortality after surgery, one patient succumbed to pneumonia in the medical arm. In 3.8% of the medical patients adverse events led to discontinuation of the study, as compared to 0.8% in the surgical group. The trial revealed that laparoscopic fundoplication is a safe and very effective treatment for gastrooesopageal reflux. The procedure is associated with a very low morbidity and no mortality if carried out in experienced high-volume institutions. Symptom control after three years is more complete following operation, and quality of life scores are better in the surgical group. The treatment efficacy after longer time intervals is not yet known, and the results after more than five years will probably never turn up, since Astra-Zeneca, the manufacturer of esomeprazol, decided to discontinue the study in summer 2008. The reason for this move is not quite clear. An earlier study which compared open fundoplication with omeprazol revealed no significant results after five years, but a higher proportion of patients remaining symptom-free after seven years (L. Lundell 2007). In that trial treatment did not fail in 67% of the surgical (fundoplication) patients and in 47% of the medical group (p=0.002). Hovever, a significant difference had not shown up after shorter observation intervals, suggesting that PPI treatment lost it’s efficacy at a faster pace than fundoplication. Observational studies after laparoscopic fundoplication revealed that after a median follow-up of eight years around 12 % symptomatic recurrences were observed (J. Hafez 2008). The criteria to define treatment failure were the same as in the Lotus study. The median interval between operation and recurrence was 30 months. The majority of recurrences (14 of 16 cases; 88%) were encountered within 36 months after surgery, and no recurrence had arisen later than 69 months postop. Should the recurrences behave similarly in the Lotus study, superior and longer-lastig reflux control should be expected in the fundoplication group. It is therefore very deplorabe that the sponsor terminated the study before longer lasting observations - however unfavorabe for the medical treatment group - could be evaluated.
Manufactrer sponsored 12-month observations (GB Cadiere et al. Antireflux Transoral Incisionless Fundoplication Using EsophyX: 12-Month Results of a Prospective Multicenter Study. World J Surg April 2008[online]) following endoscopic plication (”incisionless fundoplication”) were published of an open multicenter study - without sham-treated controls - using the EsophyX device. As in previous similar trials of endoscopic anti-reflux treatments the procedure resulted in an amelioration of symptoms and decreased use of proton oump inhibitor drugs (PPI). Esophageal pH-monitoring revealed “normalization ” of acid exposure ( i.e. pH below 4 in ≥ 5.3% of the monitoring time) in only 37% of the cases after 12 months. The median fraction time with a pH below 4 was 10% before the procedure, and 7 % after 6 and 12 months. There were three serious adverse events among the 86 patients: A perforation of the proximal oesophagus which was sutured surgically. A perforation of the hypopharynx, that was repaired surgically as well. And gastric bleeding following the procedure, requiring transfusion of 4 units of blood and endoscopic application of clips and fibrin glue. All three patients were discharged after 5 to 21 days. Although data show some moderate reduction of gastroesophageal reflux in the first 12 months after the endoscopic procedure, there is still no convincing evidence that any endoscopic treatment can be recommended as safe and effective, such as are laparoscopic fundoplication or long-term PPI treatment. There remain major uncertainties concerning the safety of the procedure and the durability of the therapeutic effects. Morover, it is unclear, whether this procedure- in case of failure - does not interfere with the safety and effectiveness of later attempted laparoscopic fundoplication. If a patient desires an alternative to long-term treatment with PPI for GERD, laparoscopic fundoplication at the moment is still unchallenged in the completeness of reflux control and reliable effectiveness over a long period of time.
An editorial in Lancet (M Anvari. Endoscopic treatments for gastro-oesophageal reflux disease. Lancet 2008: 371: 965-6.) recently highlighted a profound review paper by Fry and Mönkemüller on endoscopic therapies for GERD. In this systematic review only 43 publications out of 4182 retrieved articles met the inclusion criteria: at least 10 cases, follow-up more than 3 months, no studies on children, no abstracts. Only 4 (four) of the 43 papers were randomized, sham-controlled trials. The editorialist emphasized that ” despite some short-term improvements in symptom control and decreased use of proton-pump inhibitors reported with many of the endoluminal techniques, no study of any techniques has provided adequate ‘ scientific and clinical data on their safety, sfficacy and durability to support the use of endoluminal therapies for GORD [ ] in routine clinical practice.’ ”
An abundance of endoscopic procedures and devices for the treatment of GERD has emerged in the past, have made some shakeup and - deceased in peace. The excellent results of surgical and pharmacological treatment of GERD - lately confirmed by prospective randomized studies - remain the gold standard with which new treatment options have to measured. New endoscopic approaches continue to come forth lacking the sound evaluation and long follow-up results of fundoplication and therapy with proton pump inhibitors. It is therefore my intention to shed light on the natural history of endoscopic treatment trials by reviewing published evidence and also by giving a rundown of the economic fate of involved companies.
Hafez J*, Wrba F°, Lenglinger J*, Miholic J*
SURGICAL ENDOSCOPY ( Published online: 1 May 2008)
Medical University Vienna/Department of Surgery; °Medical Univeristy Vienna/Department of Pathology;
+43 40400 65 65
johannes.miholic@meduniwien.ac.at
Background: The impact of the mode of operation (partial versus total fundoplication) on long-term outcome is still unknown, although short-term randomized studies have not shown significant differences in the efficacy of reflux control. In order obtain some insight on long-term results the data of an unrandomized cohort was analysed using propensity score statistics.
Subjects and methods: In 133 patients having undergone laparoscopic fundoplication for gastroesophageal reflux disease (GERD) the time to recurrence of reflux symptoms was assessed. The impact of putative prognostic factors and the mode of operation (partial vs. total fundoplication) on outcome were tested for significance using univariate and multivariate statistics including the propensity score correcting for non-randomized treatment groups. Follow-up was 60 to 123 (median: 88) months. 45 patients had a partial (Toupet) fundoplication and 89 patients a total (Nissen) fundoplication performed.
Results: The rate of recurrence after 93 months, which was the median follow-up interval, was 14% after Nissen and 9% after Toupet fundoplication (NS) as estimated according to Kaplan and Meier. Massive acid exposure to the esophagus was associated with an increased risk of recurrence: 23% in patients with a DeMeester score ≥ 50, but only 9% in cases with less severe reflux (DeMeester score < 50; p< 0.05). Multiple proportional hazard regression using the propensity score did not reveal additional significance for the variables age, gender, presence of a Barrett esophagus and mode of operation.
Conclusions: The mode of operation did not substantiate a significant impact on the efficacy of laparoscopic fundoplication in a cohort with a 60 to 123 (median: 88) months.
The doctoral thesis supervisor’s comment:
An den Curriculumsdirektor der Medizinischen Universität Wien
Betrifft: Dissertation cand.med. Joumanah Hafez
Die Dissertation:
„Analysis of prognostic factors for the longterm-efficacy of laparoscopic Nissen and Toupet fundoplication using Cox-Regression and propensity score.“
liegt zur Begutachtung vor.
Es handelt sich um ein aktuelles, in der Literatur noch kaum untersuchtes Thema: die Langzeitperformance der laparoskopischen Fundoplicatio, d.h. die Ergebnisse nach 6 bis 10 Jahren.
Im wesentlichen wird das prospektiv gesammelte Datenmaterial einer Kohorte statistisch analysiert, wobei als Endpunkt die Zeit bis zum Rezidiv, d.h. bis zum Therapieversagen analysiert wird.
Dabei kommen bisher zu diesem Thema noch nie in der Literatur verwendete statistische Methoden zur Anwendung, der propensity score, die einen Vergleich nicht randomisierter Therapievarianten erlauben.
Die Arbeit ist formal korrekt aufgebaut, in einem guten Englisch verfasst und mit einem umfangreichen Literaturverzeichnis ausgestattet.
Sie gliedert sich in eine genauere Darstellung des fachlichen Hintergrunds, und einer Darstellung der Ziele der Untersuchung.
Die Methodik wird im nächsten Abschnitt präzise festgelegt.
Es folgt eine genaue und anschauliche Darstellung der Ergebnisse, und schließlich der Kommentar und die Diskussion der Ergebnisse.
Ich halte die Dissertation für außergewöhnlich gut gelungen.
als zweiten Gutachter schlage ich vor:
Herrn Prof.Dr. Michael Bergmann, Klinik für Chirurgie, MUW
There exists abundant literature on reflux, fundoplication, end stage lung disease, bronchiolitis obliterans and lung transplantation. A review will appear here soon.
Willkommen beim neuen Blog reflux advanced surgery. Der gastroösophageale Reflux ist ein verbreitetes Leiden geworden, und es bemühen sich zwei therapeutische Optionen um diese Krankheit: Der pharmakologische Ansatz - Hemmung der Säureproduktion im Magen und die chirurgische Option: Sanierung des gestörten Ventilmechanismus an Übergang von Speisröhre zum Magen.
Es ist das Ziel dieses Blogs, über Vor- und Nachteile der jeweiligen Therapien aktuell zu berichten. Dabei sollen die ausgezeichneten Ergebnisse der Operation, also der Fundoplicatio, die wegen der nicht vorhandenen Werbebudgets der chirurgischen Profession gerne in der öffentlichen Debatte untergehen, gewürdigt werden.
Der Initiator dieser Seite hat 20 Jahre Erfahrung in der chirurgischen Therapie des gastroösophagealen Refluxes, und beschäftigt sich ebensolange mit den Konsequenzen chirurgischer Eingriffe im oberen Gastrointestinaltrakt, die oft weitgehende Folgen für Ernährung und Metabolismus zeitiigen.
Die Beiträge wenden sich an interesierte Laien ebenso, wie an Ärzte. Je nach Schwerpunkt werden sie auf Deutsch oder Englisch erscheinen. Wenn Ihnen die Seite gefällt, empfehlen Sie und weiter!