A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video)

doi:10.1016/j.gie.2019.01.013

Gastrointestinal Endoscopy

Volume 90, Issue 1, July 2019, Pages 64-74.e3

Presented at Digestive Disease Week, June 2018, Washington DC (Gastrointest Endosc 018;87:AB144-5).

https://doi.org/10.1016/j.gie.2019.01.013 Get rights and content

Background and Aims

Self-expanding metal stents (SEMSs) when deployed across the gastroesophageal junction (GEJ) can lead to reflux with risks of aspiration. A SEMS with a tricuspid antireflux valve (SEMS-V) was designed to address this issue. The aim of this study was to evaluate the efficacy and safety of this stent.

Methods

A phase III, multicenter, prospective, noninferiority, randomized controlled trial was conducted on patients with malignant dysphagia requiring SEMSs to be placed across the GEJ. Patients were randomized to receive SEMSs with no valve (SEMS-NV) or SEMS-V. Postdeployment dysphagia score at 2 weeks and Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) questionnaire score at 4 weeks were measured. Patients were followed for 24 weeks.

Results

Sixty patients were randomized (SEMS-NV: 30 patients, mean age 67 ± 13 years; SEMS-V: 30 patients, mean age 65 ± 12 years). Baseline dysphagia scores (SEMS-NV, 2.5 ± .8; SEMS-V, 2.5 ± .8) and GERD-HRQL scores (SEMS-NV, 11.1 ± 8.2; SEMS-V, 12.8 ± 8.3) were similar. All SEMSs were successfully deployed. A similar proportion of patients in both arms improved from advanced dysphagia to moderate to no dysphagia (SEMS-NV, 71%; SEMS-V, 74%; 95% confidence interval, 1.93 [–17.8 to 21.7]). The dysphagia scores were also similar across all follow-up time points. Mean GERD-HRQL scores improved by 7.4 ± 10.2 points in the SEMS-V arm and by 5.2 ± 8.3 in the SEMS-NV group (P = .96). The GERD-HRQL scores were similar across all follow-up time points. Aspiration pneumonia occurred in 3.3% in the SEMS-NV arm and 6.9% in the SEMS-V arm (P = .61). Migration rates were similar (SEMS-NV, 33%; SEMS-V, 48%; P = .29). Two SEMS-V spontaneously fractured. There was no perforation, food impaction, or stent-related death in either group.

Conclusions

The SEMS-V was equally effective in relieving dysphagia as compared with the SEMS-NV. Presence of the valve did not increase the risks of adverse events. GERD symptom scores were similar between the 2 stents, implying either that the valve was not effective or that all patients on proton pump inhibitors could have masked the symptoms of GERD. Studies with objective evaluations such as fluoroscopy and/or pH/impedance are recommended. (Clinical trial registration number: NCT02159898.)

Graphical abstract

Section snippets

Methods

This was a phase III, prospective, single-blinded, noninferiority, randomized controlled study comparing the efficacy of a novel stent with an antireflux valve (SEMS-V) with a standard stent with no valve (SEMS-NV). Eight U.S. centers participated in this study. The study was conducted in accordance with the International Conference on Harmonization for Good Clinical Practice and the appropriate regulatory requirements. Local institutional review board approval was obtained by each center, and

Results

The demographics of the patient population are summarized in Table 1. Most were receiving chemotherapy and had comorbidities including metastasis (SEMS-NV, 36.7%; SEMS-V, 31.0%), cardiac disorders (SEMS-NV, 36.7%; SEMS-V, 27.6%), infections (SEMS-NV, 23.3%; SEMS-V, 41.4%), and renal disorders (SEMS-NV, 33.3%; SEMS-V, 20.7%). Baseline dysphagia scores were identical in the 2 arms. Baseline GERD-HRQL scores were also similar in the 2 groups. Technical success in placing stents was 100%. Because

Discussion

In 2018, 17,290 cases of esophageal cancer were diagnosed in the United States.⁸ Most of these patients will have advanced disease requiring palliation.⁸ Among all modalities used for dysphagia palliation, SEMSs have been shown to rapidly relieve dysphagia with minimal morbidity.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20 Because adenocarcinomas are located at the lower third of the esophagus, SEMSs must be deployed across the GEJ. Despite taking PPIs, these patients are at risk of GER and

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Cited by (11)

AGA Clinical Practice Update on the Optimal Management of the Malignant Alimentary Tract Obstruction: Expert Review
2021, Clinical Gastroenterology and Hepatology
Citation Excerpt :
In fact, gastroesophageal reflux has been reported in 70%–100% of cases with esophageal SEMS placement. Recently, there has been extensive research into the development of anti-reflux mechanisms (including anti-reflux valves); however, a definitive mechanism has yet to be determined.23 For patients with malignant esophageal obstruction who are undergoing SEMS placement, clinicians should use a FCSEMS or PCSEMS and not an UCSEMS, with consideration of a stent-anchoring/fixation method.
The purpose of this expert review is to describe the current methodologies available to manage malignant alimentary tract obstructions as well the evidence behind the various methods (including their efficacy and safety), indications, and appropriate timing of interventions.
This is not a formal systematic review but is based on a review of the literature to provide best practice advice statements. No formal rating of the quality of evidence or strength of recommendation is carried out.
For all patients with alimentary tract obstruction, the decision about specific interventions should be made in a multidisciplinary setting including oncologists, surgeons, and endoscopists and take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.
For patients who present with esophageal obstruction from esophageal cancer and who are potential candidates for resection or chemoradiation, clinicians should not routinely insert a self-expanding metal stent (SEMS) without multidisciplinary review because of high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.
For patients who present with esophageal obstruction from esophageal cancer who are potential candidates for resection and who have concerns of malnutrition, clinicians may consider the use of enteral feeding tubes (via nasogastric or percutaneous route). Clinicians should be aware of the potential risk of abdominal wall tumor seeding as well as making subsequent gastric conduit formation difficult with percutaneous endoscopic gastrostomy placement.
For patients who present with esophageal obstruction from esophageal cancer who are not candidates for resection, clinicians should consider either SEMS insertion or brachytherapy as sole therapy or in combination. Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives.
For patients with malignant esophageal obstruction who are undergoing SEMS placement, clinicians should use a fully covered or partially covered SEMS and not an uncovered SEMS, with consideration of a stent-anchoring/fixation method.
For patients with gastric outlet obstruction who have a life expectancy greater than 2 months, have good functional status, and who are surgically fit, surgical gastrojejunostomy should be considered.
For patients with gastric outlet obstruction who are undergoing surgical gastrojejunostomy, a laparoscopic approach is favored over an open approach because of lower blood loss and shorter hospital stay.
For patients with gastric outlet obstruction who are not candidates for gastrojejunostomy (surgical or endoscopic ultrasound-guided), clinicians should consider the insertion of an enteral stent.
Enteral stents should not be used in patients with multiple luminal obstructions or severely impaired gastric motility because of the limited benefit in these scenarios. Clinicians can consider placement of a venting gastrostomy in these patients.
Depending on the experience of the endoscopist, endoscopic ultrasound-guided gastrojejunostomy is an acceptable alternative to surgical gastrojejunostomy and enteral stent placement. Clinicians should be aware that there are currently no dedicated Food and Drug Administration–approved devices for endoscopic ultrasound–guided gastrojejunostomy.
For patients with malignant colonic obstruction who are candidates for resection, insertion of SEMS is a reasonable choice as a “bridge to surgery” to allow for one-stage, elective resection.
For patients with malignant colonic obstruction who are not candidates for resection, either SEMS placement or a diverting colostomy are reasonable choices depending on the patient’s goals and functional status.
SEMS is a reasonable option for patients with proximal (or right-sided) malignant obstructions, both as a “bridge to surgery” and in the palliative setting.
SEMS placement is a reasonable alternative for patients with extracolonic malignancy who are not candidates for surgery, although their placement is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.
Antireflux esophageal stents: Do we have a winner?
2019, Gastrointestinal Endoscopy
Best Practices in Esophageal, Gastroduodenal, and Colonic Stenting
2023, GE Portuguese Journal of Gastroenterology
Endoscopic Stenting for Malignant Dysphagia in Patients with Esophageal Cancer
2023, Current Oncology
25 Years of the GERD-HRQL symptom severity instrument: an assessment of published applications
2023, Surgical Endoscopy
Anti-reflux versus conventional self-expanding metal stents in the palliation of esophageal cancer: A systematic review and meta-analysis
2022, Endoscopy International Open

View all citing articles on Scopus

: DISCLOSURE: The following authors disclosed financial relationships relevant to this publication: K. S. Dua: Grant recipient from Boston Scientific, Cook Medical, and Merit Medical; speaker for Boston Scientific. J. M. DeWitt: Consultant for Olympus America, Boston Scientific, and Pinnacle Biologics. W. R. Kessler, P. V. Draganov: Grant recipient from Merit Medical, consultant for Cook, BSC, Olympus, Microteck, and MicroTech; Merit and paid speaker for Cook, BSC, and Olympus. D. L. Diehl: Consultant for Merit Medical. M. S. Wagh: Consultant for Boston Scientific and Medtronic. M. Kahaleh: Grant recipient from Merit Medical, Olympus America, Boston Scientific, Cook Medical, Aspire Bariatrics, GI Dynamics, Apollo, Fuji, Pentax, Emcision, Concordia, MI Tech, Maunakea Tech, Ninepoint Medical, and W.L. Gore. S. A. Edmundowicz: Medical advisory board member for Endostim, Check-Cap, Motus GI, Elira, and Olympus; stock options from Endostim, Check-Cap, Motus GI, and Freehold Surgical; stockholder for Elira (also spouse), Aspero Medical Inc, UV Concepts Incorporated (spouse), and Motus GI (spouse); consultant for Motus GI, Olympus, Medtronic, and Allurion; co-founder of Aspero Medical Inc; paid associate editor for Elsevier; Data Safety Monitoring Board Chair for Allurion. B. C. Brauer: Consultant for Boston Scientific and Medtronic; grant recipient from Erbe. D. G. Adler: Consultant for Boston Scientific and Merit Medical. L.M. Wong Kee Song: grant from Merit Medical. All other authors disclosed no financial relationships relevant to this publication. Research support for this study was provided by Merit Medical.

: See CME section; p. 150.

: If you would like to chat with an author of this article, you may contact Dr Dua at [email protected].

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Original articleClinical endoscopyA phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video)

Background and Aims

Methods

Results

Conclusions

Graphical abstract

Section snippets

Methods

Results

Discussion

Gastroenterology

Clin Gastroenterol Hepatol

Gastrointest Endosc Clin North Am

Gastrointest Endosc Clin North Am

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Cancer incidence and mortality risks in a large US Barrett's oesophagus cohort

Gut

Introduction: esophageal adenocarcinoma: updates of current status

Methods Mol Biol

Cancer, esophageal. Treasure Island

Cancer stat facts: esophageal cancer

Self-expanding metallic stents and self-expanding plastic stents in the palliation of malignant oesophageal dysphagia

Ann Palliat Med

The development of the GERD-HRQL symptom severity instrument

Dis Esophagus

Outcome and risk factors assessment for adverse events in advanced esophageal cancer patients after self-expanding metal stents placement

Dis Esophagus

Clinical outcomes of esophageal stents in patients with malignant esophageal obstruction according to palliative additional treatment

J Dig Dis

The role of stents in the palliation of oesophageal cancer

BMJ Support Palliat Care

Quality of life in patients with esophageal stenting for the palliation of malignant dysphagia

World J Gastroenterol

Original article
Clinical endoscopy
A phase III, multicenter, prospective, single-blinded, noninferiority, randomized controlled trial on the performance of a novel esophageal stent with an antireflux valve (with video)