El procedimiento EndoStim:

Resúmenes y publicaciones seleccionados (DDW y SAGES 2016):

Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter (LES) for Refractory GERD - One Year Results of an International Multicenter Trial?

Peter D. Siersema, Albert J. Bredenoord, José M. Conchillo, Albis C. Hani, Michael Booth, Alex Escalona, Abraham Botha, Justin C. Wu, Nageshwar D. Reddy, Gonzalo TorresVillalobos, Philip W. Chiu, Nicole D. Bouvy, Mark I. van Berge Henegouwen, Jelle P. Ruurda, Nicolas Quezada, Miguel A. Valdovinos

BACKGROUND: A long-term single-center trial showed that LES-EST significantly improves esophageal acid exposure and symptoms in GERD patients (Surg Endosc. 2015;DOI10.1007/s00464-015-4539-5).

AIM: To establish safety and efficacy of LES-EST in GERD patients partially responsive to PPI in an international multi-center trial.

METHODS: We studied GERD patients partially responsive to proton pump inhibitors (PPI) with off PPI GERD-HRQL >20 and at least 5 point improvement on-PPI, LES end-expiratory pressure at least 5mmHg, % 24 hour esophageal pH<4 for at least 5%, hiatal hernia <3cm and esophagitis <LA Grade C. Bipolar stitch electrodes and a pulse generator (EndoStim BV) were implanted laparoscopically. EST at 20Hz, 220usec, 4-6mAmp in 12 30-minute sessions was initiated post-implant. GERD related outcomes were evaluated at regular intervals.

RESULTS:Forty-two patients (median 51 yr; 24 men) were enrolled and implanted with an LES stimulator; 37 completed 12-month follow-up. Median(IQR) GERD-HRQL improved from 31(26-37) off-PPI and 17(9-23) on-PPI at baseline to 5(2-9) at 12 mo. (p<0.001 vs. BL on and offPPI). Median esophageal acid exposure (pH<4.0) improved from 10.0(7.6-12.9)% at baseline to 4.4(2.5-6.4)% at 12 mo. (p<0.001). At 12 mo. 81% were completely off PPI, 8% used PPI intermittently (<50% days) and 11% used PPI regularly (>50% days). Median SF-12 mental health score improved from 48 on-PPI and 45 off-PPI at baseline to 53 at 12 mo. (p=0.096 vs. BL on-PPI; p<0.01 vs. off-PPI). Median SF-12 physical health score improved from 45 on-PPI and 39 off-PPI at baseline to 50 at 12 mo. (p<0.001 vs. BL on and off-PPI). Median activity impairment, measured by the WPAI:GERD questionnaire, improved from 20% at baseline on-PPI and 60% off-PPI to 0% at 12-mo. (p<0.001 vs. BL on and off-PPI). Four SAEs were reported. Two were asymptomatic electrode erosions related to the device and/or procedure; both patients reported loss of therapy efficacy and underwent uneventful fundoplication surgery during which the device was explanted. One was a procedure-related laparoscopic trocar perforation of the small bowel during the implant procedure, successfully repaired laparoscopically. One was an AV nodal reentrant tachycardia, not related to the device or therapy, successfully treated with AV nodal ablation. Five instances of dysphagia were reported in 4 patients with a hiatal closure procedure at the time of implant, all resolved without intervention. Other device and/or procedure related events were typical of surgical implant procedures, e.g. nausea and pocket pain.

CONCLUSION: One-year results of this multicenter trial show that LES-EST is safe and effective for treating PPI partially responsive GERD, validating previous reports. LES-EST resulted in significant improvement in esophageal acid exposure, GERD symptoms, PPI usage and quality of life, with excellent safety and tolerability.


Preliminary Results of a Prospective Multi-Center Observational Registry of Lower Esophageal Sphincter Stimulation for GERD: The Less-GERD Registry?

Joachim Labenz, Henning G. Schulz, Andreas Leodolter, Jan B. Pedersen, Ernst Eypasch, Alejandro Nieponice, Ralf Weise, Nicole D. Bouvy

BACKGROUND: Electrical stimulation of the lower esophageal sphincter (LES-ES) using the EndoStim® LES Stimulation System (The Hague, The Netherlands) was shown to be effective and safe in clinical trials. Data from routine clinical practice has not yet been reported.

METHODS: An ongoing, prospective multicenter web-based registry is collecting data at baseline and at routine follow-ups for 5-year in patients with disruptive GERD symptoms treated with LES-ES in routine clinical practice. Demographics, adverse events, GERD symptoms recorded in daily diaries, GERD health related quality of life scores (GERD-HRQL), structured GI symptom questionnaires for extra-esophageal symptoms, use of proton pump inhibitors (PPIs) and objective endoscopic and physiological data (esophageal pH / manometry) are collected when available.

RESULTS: Eighty-nine patients are enrolled in the LESSGERD Registry, of whom 39 have available data at baseline and 6 months post-op. All but three (36/39; 92%) patients showed an improvement in their GERD-HRQL score on LESES compared to baseline. Overall, the median (IQR) composite GERD-HRQL score improved from 22 (18-27) preoperatively to 8.0 (3.5-12.5) at 6-month follow-up (p <0.0001). Median distal esophageal acid exposure improved from 11.7 (5.0-24.0)% at baseline to 5.1(2.0- 12.6)% at 6 months (n=17; p=0.59). Proportion of patients with moderate to severe regurgitation decreased from 70% while on medication therapy preoperatively to 27% after 6 months of LES-ES (p<0.04). Proportion of patients with bothersome reflux symptoms during sleep improved from 71% pre-op to 20% at 6 months (p<0.004). Proportion of patients with recurrent cough improved from 40% (6 patients) preoperatively to 10% after 6 months (1 patient). One patient reported severe dysphagia pre-op that was resolved post-op. There was no change in the rate of occasional dysphagia reported. All patients were on long-term PPI at baseline. At 6 months, 17 (80%) patients were completely free of PPI use, 3 patients (8%) used PPI occasionally and only 5 patients (13%) were still taking daily PPI. Final safety data being analyzed and adjudicated by independent DSMB and will be reported at the meeting.

CONCLUSION: In routine clinical practice, LES-ES is safe and effective in treating GERD patients with disruptive GERD symptoms despite PPI with improvement across all reported outcomes. LES-ES may be considered a viable treatment option for this indication.


Effect of Electrical Stimulation Therapy of the Lower Esophageal Sphincter on Postprandial Reflux Mechanisms in GERD Patients

Nicolaas F. Rinsma, Boudewijn F. Kessing, Nicole D. Bouvy, Mark I. van Berge Henegouwen, Andreas J. Smout, Albert J. Bredenoord, Ad Masclee, José M. Conchillo

BACKGROUND: Two open-label trials have shown that Electrical stimulation therapy (EST) of the lower esophageal sphincter (LES) (LES-EST) significantly improves esophageal acid exposure and symptoms in GERD patients. However, the underlying antireflux mechanism(s) of LES-EST remain(s) unclear.

AIM: The aim of this study is to evaluate the effect of EST on postprandial reflux mechanisms, especially on transient LES relaxations (TLESRs).

METHODS: We studied 10 chronic GERD patients with abnormal acid exposure (pH<4.0 during > 6% of time) and hiatal hernia <3 cm (3 males; mean age 53, range 32-66 yrs). Bipolar stitch electrodes and a pulse generator (EndoStim BV, The Hague, Netherlands) were implanted during laparoscopic surgery. LES-EST was delivered at 20 Hz, 220 µs, 5 mA in 12 30- minute sessions. Postprandial reflux mechanisms were studied before and 3 months after EST-implantation, using a combined stationary high-resolution manometry (HRM) and impedance-pH monitoring. Patients consumed a standardized high caloric (500 kCal) meal (cheeseburger, crisps and 200 ml orange juice), followed immediately by a 90-minute measurement. Patients remained in a semi-recumbent position during the measurement and were not allowed to sleep.

RESULTS: The majority of postprandial reflux episodes occurred during TLESRs, both before (77%) and after (63%) EST-implantation. After LES-EST, a significant reduction in the total number of TLESRs (from 9.1 (4.0) to 5.6 (3.2), p<0.01) and in the number of TLESRs associated with reflux episodes (from 6.7 (4.1) to 3.8 (3.6), p=0.04) was observed. Total postprandial reflux episodes were not significantly altered by LES-EST (from 9.0 (5.1) to 6.8 (6.1), p=0.14); however, the number of reflux episodes facilitated by TLESRs was significantly reduced (7.0 (3.6) to 3.9 (3.4), p=0.03). The number of reflux episodes induced by other mechanisms (such as abdominal straining or swallow induced) were unaffected by the treatment. EST showed no effect on the duration of TLESRs (from 17.5 4.3) s to 14.4 (5.7) s, p=0.14) nor on LES resting pressure (from 19.2 (11.3) mmHg to 21.1 (14.9) mmHg, p=NS).

CONCLUSION: Electrical stimulation therapy of the LES reduced the total number of postprandial TLESRs as well as the number of TLESR-associated reflux episodes in GERD patients. These results suggest that the effect of LES-EST on acid exposure and GERD symptoms is primarily TLESR-mediated.


Electrical Stimulation Therapy (EST) of the Lower Esophageal Sphincter(LES) is Successful in Treating GERD - Long-term 4 Year Results?

Leonardo Rodriguez, Patricia Rodriguez, Beatrice Gómez, Manoel Galvao Neto, Michael Crowell, Edy Soffer

BACKGROUND: We have previously reported that LES-EST has improved in outcomes in patients with GERD at 3 year follow-up (Surg Endosc. 2015; DOI 10.1007/s00464-015-4539-5).

AIM: The aim of this open-label human pilot trial registry was to study the safety and efficacy of LES-EST in the cohort of GERD patients over longer 5-year follow-up. We report the results at 4 year.

METHODS: GERD patients at least partially responsive to proton pump inhibitors (PPI) and had off-PPI GERD HRQL>20, % 24 hour esophageal pH<4.0 for >5%, hiatal hernia < 3cm and esophagitis < LA Grade C have been treated with LES-EST (EndoStim BV, the Hague, the Netherlands). Patients were evaluated using GERD-HRQL, symptom diaries, and esophageal pH testing at their 4 year follow-up.

RESULTS: Twenty five patients (mean (SD) age= 53 (12) years; men=14) were successfully implanted, 21 agreed to participate in the long-term registry trial and 15 completed their 4-year evaluation. At 4 years on LES-EST, median (IQR) GERD-HRQL was 3 (1-3), significantly improved from 9 (8-10) at baseline on-PPI (p=0.004) and 24 (21-25) at baseline off-PPI (p<0.001). Median 24-hour distal esophageal acid exposure significantly improved from 10.2 (7.9- 11.5)% at baseline to 3.6 (2.8-6.6)% at 4 year (p<0.02). Seventy-nine % (11/14) of patients who received continuous therapy for 48 months experienced normalization or at least 50% improvement of their distal esophageal acid exposure. All but 2 patients reported cessation of regular PPI use (>50% of days with PPI use). There were no unanticipated device- or stimulation-related adverse events, or untoward sensation reported between 3 and 4 year follow-up. There was one procedure related SAE – “hiatal hernia mesh related coronary artery erosion and resulting cardiac tamponade” requiring laparoscopic exploration and repair of the coronary erosion. Patient had a prolonged hospital stay and recovered uneventfully from the complication.

CONCLUSION: LES-EST is safe and effective for treating patients with GERD over a long-term 4-year duration. There was a significant and sustained improvement in symptoms, esophageal acid exposure and reduction in PPI use. Further, LES-EST is not associated with any GI side-effects or adverse events.


EndoStim LES Stimulation Therapy Improves GERD in Patients with Laparoscopic Sleeve Gastrectomy (LSG)

Alejandro Nieponice, Yves Borbély, Leonardo Rodriguez, Henning G Schulz, Camilo Ortiz, Michael Talbot, David Martin, Nicole Bouvy

LSG is the most commonly performed bariatric procedure in the US/Canada and the Asia-Pacific region. However, LSG can result in new GERD and may worsen pre-existing GERD. LSG patients with GERD not well controlled with PPI do not have good treatment options except for more invasive, anatomy-altering gastric bypass surgery. LES electrical simulation therapy has shown to improve outcomes in GERD patients.

AIM: To evaluate the safety and efficacy of LES stimulation in LSG patients with GERD not controlled with maximum dose PPI therapy.

METHODS: Patients with LSG associated GERD with bothersome symptoms on maximum PPI dose underwent LES stimulator implant procedure and were enrolled in an international patient registry prospectively tracking outcomes in GERD patients treated with LES electrical stimulation. Electrical stimulation was delivered at 5mA, 220uSec pulse in 12, 30 minute sessions daily. GERD outcomes pre and post-stimulation were evaluated.

RESULTS: 12 patients, 66% (8/12) women at 8 centers have been treated. Median age was 46 (IQR=34-55) years. All (12/12) were on at least daily double-dose PPIs. At their last follow-up (median=12 months), 75% (6/8) were off-PPIs and one each was using PPIs on < 50% of days and standard dose once a day. The later was on daily PPI for GI prophylaxis for chronic steroid therapy for kidney transplants and not GERD symptoms. Median esophageal pH at baseline was 16.4% (IQR 8.5-22.4), which improved to 1.3% (IQR 0.4-2.2) % at last follow-up at least 6 month post-implant (n=6; p=0.01). All patients improved esophageal acid exposure, 83% (5/6) patients had normalized acid exposure and 1/6 patient had >40% improvement in distal esophageal acid exposure. Median GERD-HRQL scores at baseline was 25 (IQR 18-31) which improved to 4 (IQR 3-10) at last follow-up (n=6; p= 0.015). No SAEs related to the device or procedure were reported. No dysphagia or other GI side effects were reported.

CONCLUSION: Preliminary results on patients with LSG and GERD with bothersome symptoms despite maximal medical therapy, treated with LES electrical stimulation, revealed that LES stimulation is safe and results in a significant improvement in GERD symptoms and esophageal acid exposure. Most patients were off their PPI therapy with remaining taking PPI at a reduced dose. Data from a larger patient experience for this indication is being collected using the international registry trial.