Interventional procedure overview of endoluminal gastroplication for gastro-oesophageal reflux disease
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Summary of key evidence on endoluminal gastroplication for gastro-oesophageal reflux disease
Study 1 Grössmann (2021)
Study type | Systematic review (undertaken as part of a HTA) |
|---|---|
Country | USA, Netherlands, Belgium, France, Sweden |
Search period | Search date 2020: publications from previous 10 years (no start date reported) |
Study population and number | N=580 patients across 8 studies with chronic GORD |
Age and sex | Intervention groups: median age 51 to 55 years Comparison groups: median age 48 to 62 years |
Patient selection criteria | Inclusion criteria: Studies with adult patients with chronic GORD (>6 months) with at least 1 typical reflux symptom despite PPI treatment; patients having endoscopic plication therapy (one of GORDx, EsophyX and MUSE); control groups of placebo, standard surgical treatment of GORD or PPI therapy; RCTs, prospective non-RCTs, or prospective single-arm studies & registries with n≥100 (safety only); publications from the last ten years. |
Technique | Interventions: Patients were assigned to endoscopic plication using EsophyXZ (Gastric Solutions, Redmond, Wash, USA), Medigus Ultrasonic Surgical Endostapler (MUSE; Medigus Ltd, Omer, Israel) or GORDx (G-SURG GmbH, Seeon-Seebruck, Germany) Controls: Patients were assigned to PPI therapy, sham intervention or laparoscopic reflux surgery (depending on the study). |
Follow up | 3 months to 5 years |
Conflict of interest/source of funding | None. |
Analysis
Study design issues: The HTA Core Model Application for Rapid Relative Effectiveness Assessment (REA; 4.2) was the primary source for selecting assessment elements.
To identify primary studies containing information about efficacy and safety within the scope of the HTA, systematic literature searches were conducted using Medline, Embase, the Cochrane Library, CRD (DARE, NHS-EED, HTA) and HTA-INAHTA. To identify ongoing and unpublished studies, a search in 3 clinical trials registries (ClinicalTrials.gov; WHO-ICTRP; EU Clinical Trials) was also done and manufacturers of relevant devices contacted.
Two researchers independently screened entries, and in the case of disagreements, a third researcher was involved to resolve the differences. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs, the Risk of Bias In Non-randomised Studies of Interventions assessment tool (ROBINS-I) for non-randomised controlled studies (NRCTs) and the International Health Economics checklist for single-arm studies.
The quality of the body of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology in which "high" = confidence that the true effect lies close to the estimate of the effect; "moderate" = moderate confidence in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different; "low" = confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect; and "very low" = Evidence either is unavailable or does not permit a conclusion.
The following outcomes were deemed "crucial" to obtain a recommendation: heartburn score, regurgitation score, health related quality of life, adverse events (including serious adverse events), death and surgical reintervention.
Study population issues: All studies included chronic GORD patients. All identified studies included chronic GORD patients with a history of daily PPI use over the last six months. Patients with a hiatal hernia of more than two centimetres were excluded from all trials except for two studies that also enrolled patients with hiatal hernias up to three centimetres.
Other issues: Some studies included in this HTA used former generations of the devices used in this study which are no longer available on the market.
There is patient overlap with the McCarty 2018 systematic review in the case of the following studies: Witteman (2015), all included Trad studies (as well as the Trad 2018 study included in Table 2), Håkansson (2015) and Hunter (2015).
Key efficacy findings
Number of patients analysed: 580
a = 3/4 high RoB, 1/4 moderate RoB,
b = different trends of improvements comparing treatment groups
c = different generation of devices
d = power calculations are lacking
e = high RoB
f = 1/2 high RoB, 1/2 moderate RoB
Key safety findings
Outcomes | Impact | No. of studies (patients on intervention vs control) | Certainty of the evidence (Importance) |
Any adverse event (Any AEs) assessed with: number of patients follow up: range 3 to 12 months | 1 study reported a ss improvement in bloating between study groups (p=0.009), but no ss difference between groups considering dysphagia (p=0.366), 1 study reported more percentages of patients suffering from moderate to severe AEs in the intervention group compared with the control group, 2 studies reported no ss differences between study groups | 4 RCTs (186 vs. 120) | VERY LOW b,c,g (Crucial) |
Any AEs assessed with: discharge time Follow up: mean 6 months | The mean discharge times for the control and the intervention groups were 1.2 and 3 days, respectively (p<0.05), except for one complicated patient in the intervention group who stayed 21 days. | 1 NRCT (11 vs. 16) | LOW d,e (Crucial) |
Any AEs assessed with: number of patients Follow up: range 6 to 24 months | Overall dysphagia, bloating and flatulence improved comparing baseline and 6-months follow up. After 12-month follow up de novo dysphagia (n=2), bloating (n=1), and flatulence (n=2) occurred. After 24-month follow up, de novo flatulence occurred in 2 patients. | 1 observational study (n=100) | LOW h (Crucial) |
Severe adverse events (SAEs) assessed with: number of patients Follow up: range 3 to 12 months | all 3 studies reported no ss differences between study groups | 3 RCTs (99 vs. 75) | Moderate c,i (Crucial) |
no ss difference between treatment groups (p=0.219) | 1 NRCT (11 vs. 16) | LOW d,e (Crucial) | |
SAEs assessed with: number of patients Follow up: mean 6 months | Extra hospital day due to pain, anxiety, nausea or postoperative urinary retention: 17 (13.4%) Additional 4 hospital days due to pulmonary issues: 1 (0.8%*) Re-admission 2 days after the procedure due to immediate postoperative pain: 1 (0.8%*) | 1 observational study (n=100) | LOW h (Crucial) |
Death assessed with: number of patients Follow up: range 3 to 12 months | 1 patient who had undergone interventional procedure after crossover died, death occurred 11 months after the procedure | 1 RCT (40 vs. 20) | LOW d,e (Crucial) |
No death was reported | 1 observational study (n=100) | LOW h (Crucial) | |
Re-surgery assessed with: number of patients/re-surgeries Follow up: range 3 to 12 months | 2 studies reported 18 re-surgeries 14 in the intervention group (11 endoscopic, 3 laparoscopic) and 4 in the control group (all laparoscopic) | 2 RCTs (77 vs. 53) | LOW c,e (Crucial) |
8 re-surgeries (1 endoscopic, 7 laparoscopic) | 1 observational study (n=100) | LOW h (Critical) |
*
b = different trends of improvements comparing treatment groups
c = different generation of devices
d = power calculations are lacking
e = high RoB
g = 2/4 high RoB, 2/4 moderate RoB
h = Initially 100 patients were included in the study, however, in the 24-months follow up cohort 127 patients were analysed.
i = power calculations available in 2/3 RCTs
Study 2 McCarty (2018)
Study type | Systematic review and meta-analysis |
|---|---|
Country | Not reported |
Recruitment period | 2001-2017 |
Study population and number | n=1475 patients with GORD across 32 studies |
Age and sex | Mean age 50 years, 48% male |
Patient selection criteria | Inclusion criteria: human subject studies investigating the use of TIF modality for the treatment of GORD; patients of any age in whom the presence of GORD was suspected based on clinical symptoms alone, pH monitoring, or a combination of the two. Exclusion criteria: Insufficient data; review articles; editorials; correspondence letters that did not report independent data; case series and reported studies with fewer than five patients. |
Technique | TIF was done using the EsophyX device (EndoGastric Solutions, Redmond, Washington, USA) or the Medigus Ultrasonic Surgical Endostapler system (MUSE; Medigus Ltd., Omer, Israel). |
Follow up | Mean 15.8 months (range 1.5-59 months) |
Conflict of interest/source of funding | None. |
Analysis
Study design issues: The primary aim of this study was to evaluate the feasibility, efficacy, and tolerability of TIF for the treatment of refractory GORD. Efficacy and safety of the procedure was measured by immediate technical success rate (the ability to do the procedure without issue) and serious adverse events reported during the follow up. Symptomatic improvement was measured by complete PPI therapy cessation post-procedure, and by validated pre- and post-procedure questionnaires to assess typical and atypical GORD symptoms. Partial cessation or decreased dose of PPI therapy was not considered to represent symptomatic improvement.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement outline for reporting systematic reviews was followed. Two reviewers independently screened the titles and abstracts of retrieved articles according to predefined inclusion and exclusion criteria. Any differences were resolved by mutual agreement and in consultation with a third reviewer. In the case of studies with incomplete information, contact was attempted with the principal authors to obtain additional data.
Meta-analysis was done by calculating pooled proportions, and standardised mean difference between pre- and post-procedure characteristics. Fixed-effects models were applied to pre- and post-TIF data to determine effect size and corresponding 95%.
Study population issues: Data involving 2 separate devices that do TIF were included: 30 studies (n = 1390) with EsophyX and 2 studies (n = 85) with MUSE. Among studies that included the EsophyX device, 26 studies (n = 1232) used the TIF 2.0 protocol, 3 studies (n = 138) adopted the TIF 1.0 protocol, and one study used ELF (n = 20).
A total of 24 studies (n = 1208) reported BMI, with a mean BMI of 26.1±1.7 kg/m2. Average GORD symptom duration for included patients was 8.2±2.1 years, with a mean duration of PPI therapy of 6.8±2.1 years. Hiatal hernia prior to TIF was reported in 65.6% (n=864) of patients in studies reporting this, and oesophagitis was present in 56.2% (n=672) of patients in studies reporting this. A total of 20 patients were reported to have undergone prior surgical treatment for GORD-associated symptoms (i. e. previous laparoscopic Nissen fundoplication).
Other issues: There is patient overlap with Testoni (2019), the Grossman 2021 (Study 1) systematic review in the case of the following studies: Witteman (2015), all included Trad studies (as well as the Trad 2018 study included in Table 2), Håkansson (2015) and Hunter (2015). It is also possible that the patient population in Bell (2021) study overlaps with earlier publications from the same author that are included in this systematic review.
Key efficacy findings
Number of patients analysed: 1,475 (n = 1390 EsophyX across 30 studies and n=85 MUSE across 2 studies)
Procedural success
Immediate procedural success rate (follow up range 1.5 to 59 months): 99% (95% CI 97% to 100%; 21 studies; P < 0.001, I2=45.8%).
Need for revision or surgical intervention: 7.5% (88/1176; 21 studies) -TIF revision procedure n = 19; Dor fundoplication n = 1; Toupet fundoplication n = 1; and laparoscopic Nissen fundoplication n = 67).
The majority (89.5%) of revisions were done within 6 months of the initial TIF procedure in studies where timing of re-treatment procedure was reported (6 studies). After repeat endoscopic or surgical intervention, 77.8% (7/9) patients reported improvement in studies where symptomatic improvement after re-treatment was assessed (3 studies).
Symptom and quality of life changes
GORD HRQL (all procedures, follow up range 1 to 59 months): SMD 17.72 (95% CI 17.31 to 18.14; 25 studies, n=1236; P < 0.001; I2=94%).
GORD HRQL (TIF 2.0): SMD 17.62 (95% CI 17.19 to 18.05; 15 studies, n=997; P < 0.001).
GORD HRQL (MUSE): SMD 19.93 (95% CI 17.74 to 22.13; 2 studies, n=85; P < 0.001).
GORD HRQL (TIF 1.0): SMD 16.58 (95% CI, 14.35 to 18.81; 3 studies, n=138 P; < 0.001).
GORD HRQL (ELF): SMD 33.00 (95% CI 26.15 to 39; 1 study, n=40).
Gastro-oesophageal Reflux Symptom Score (GERSS) (follow up range 6 to 24 months): SMD 23.78 (95% CI 22.96 to 24.60; 6 studies, n=507; P < 0.001; I2=98%).
Reflux Symptom Index (RSI) score (follow up 6 to 36 months): SMD 14.28 (95% CI 13.56 to 15.01; 8 studies, n=590; P < 0.001; I2=95%).
Resolution of hiatal hernia post-procedure (follow up 6 to 59 months): 91% (95% CI 83% to 98%; 12 studies; P < 0.001, I2=85.8%).
Medication requirement
Cessation of proton pump inhibitor post-procedure (follow up 1.5 to 59 months): 89% (95% CI 82% to 95%; 28 studies, n=1407; P < 0.001, I2=93.6%).
Oesophageal acid exposureHH
Oesophageal acid exposure time (all procedures, follow up 1.5 to 36 months): SMD 3.43 (95% CI 2.98 to 3.88; 15 studies, n=722; P < 0.001; I2 = 86%)
Oesophageal acid exposure time (TIF 2.0): SMD 3.61 (95% CI 3.14 to 4.08, P < 0.001)
Oesophageal acid exposure time (MUSE): SMD 3.97 (95% CI 1.236 to 6.59, P = 0.003)
Oesophageal acid exposure time (TIF 1.0): SMD 1.90 (95% CI – 3.43 to 7.23, P = 0.49)
Oesophageal acid exposure time (ELF): SMD 0.60 (95% CI – 1.23 to 2.43, P = 0.52)
Mean number of reflux episodes in a 24-hour period (all procedures, follow up 6 to 36 months): SMD 51.57 (95% CI 47.96 to 55.18; 13 studies, n=695; P < 0.001; I2 = 85%)
Mean number of reflux episodes in a 24-hour period (TIF 2.0): SMD 53.18 (95% CI 49.49 to 56.87, P < 0.001)
Mean number of reflux episodes in a 24-hour period (MUSE) SMD 70.4 (95% CI 21.84 to 118.96, P = 0.004)
Mean number of reflux episodes in a 24-hour period (TIF 1.0): SMD 10.0 (95% CI -38.85 to 58.85; P = 0.69)
Mean number of reflux episodes in a 24-hour period (ELF): SMD 7.30 (95% CI -12.85 to 27.45, P = 0.48)
DeMeester scores pre- and post-procedure (all procedures, follow up 6 to 36 months): SMD 10.22 (95% CI 8.31 to 12.12; 11 studies, n=647; P < 0.001; I2 = 65%)
DeMeester scores pre- and post-procedure (TIF 2.0): SMD 10.42 (95% CI 8.47 to 12.36; P < 0.001)
DeMeester scores pre- and post-procedure (TIF 1.0): SMD 5.01 (95% CI -4.83 to 14.86; P = 0.32)
Key safety findings
Rate of serious adverse events (follow up 1 to 59 months): 2% (95% CI 1% to 3%; 29 studies; P < 0.001; I2=54.1%).
Study 3 Testoni (2019)
Study type | Case series |
|---|---|
Country | Italy |
Recruitment period | 2007 to 2012 |
Study population and number | n=50 patients with symptomatic GORD |
Age and sex | Mean age 45 ± 16 years, 70% male |
Patient selection criteria | Inclusion criteria: Patients with symptomatic GORD. Exclusion criteria: Atypical symptoms of GORD; functional reflux; hiatal hernia longer than 3 cm, Barrett's oesophagus, oesophageal stricture, previous oesophageal, gastric or major abdominal surgery; other severe comorbidities (including collagen disease). |
Technique | Fundoplication (TIF 2.0) was done by a single endoscopist using the EsophyX device. |
Follow up | 10 years |
Conflict of interest/source of funding | None. |
Analysis
Follow up issues: 98% (49/50) of patients were clinically evaluated at 2 and 3 years, 41/49 (83.7%) after 5 years, 30/49 (61.2%) after 7 years, and 14/49 (28.6%) after 10 years. Eight patients were lost to follow up between 3 and 5 years; no other patients were lost during the subsequent follow up.
Study design issues: The aim of this single centre observational prospective study was to evaluate the clinical efficacy of TIF at 2, 3, 5, 7, and 10 years. Clinical success was defined as complete discontinuation or halved consumption of PPI therapy, while clinical failure: defined as continuation of PPI dose as before procedure.
Intra- and inter-patient characteristics, GORD-HRLQ and GORD-QUAL total scores, heartburn and regurgitation scores, morphological and functional findings were compared by Wilcoxon's and Mann-Whitney tests or Fisher's exact test, as appropriate. A P value < 0.05 was considered to be statistically significant. Data was analysed on both an intention to treat (ITT) and per protocol (PP) basis (with patients who had surgical fundoplication on follow up included in the intention to treat analysis).
Study population issues: Mean study population BMI 22±3, mean GORD-HQOL score 20±13 for patients on PPI at time of enrolment compared with GORD-HQOL score 46±19 for patients off PPI for at least 14 days before enrolment. The mean heartburn score was 18±9 and regurgitation score was 17±9. Hiatal hernia was present in 56% (28/50) of patients and 22% (11/50) patients had oesophagitis.
Other issues: Previous version of study also included in McCarty (2018) systematic review.
Key efficacy findings
Number of patients analysed: 50 (51 procedures)
Technical and clinical success
Technical success: 49/50 patients (1 failure due to intraprocedural pneumothorax, 1 failure due to device malfunction with successful repeat procedure).
2 years | 3 years | 5 years | 7 years | 10 years | |
Patients on follow up, n (%) | 45/49 (91.8) | 45/49 (91.8) | 34/49 (69.4) | 24/49 (49) | 12/49 (24.5) |
Patients who had surgical fundoplication on follow up, n (%) | 4/49 (8.2) | 4/49 (8.2) | 7/49 (14.3) | 6/49 (12.2) | 2/49 (4.1) |
Patients lost to follow up, n (%) | 0 | 0 | 8/49 (16.3) | 5/49 (10.2) | 5/49 (10.2) |
Change in symptoms
Follow up (per protocol) | Baseline (n=49) | 2 years (n=45) | 3 years (n=45) | 5 years (n=34) | 7 years (n=24) | 10 years (n=12) |
GORD-HRQL score (off PPI), mean±SD | 18 ± 13* | 19 ± 14* | 10 ± 7** | 10 ± 7.7** | 9.5 ± 6.1** | |
Heartburn score, mean ± SD | 18±9 | 8±7* | 9±8* | 4.5 ± 4.6* | 4.6 ±4.7* | 4.2 ±3* |
Regurgitation score, mean ± SD | 17±9 | 9±6* | 10± 6* | 3.2 ± 4.3* | 3.3 ±4.4* | 3.2 ±4.4* |
* = P value for outcome compared with baseline <0.01
** = P value for outcome compared with baseline <0.001
Medication usage
Medication outcome | 2 years | 3 years | 5 years | 7 years | 10 years |
Stopped PPI (PP analysis) | 25/45 (55.6) | 24/45 (53.3) | 14/34 (41.2) | 11/24 (45.8) | 5/12 (41.7) |
Stopped PPI (ITT analysis) | 25/50 (50) | 24/50 (48) | 14/42 (33.3) | 11/31 (35.5) | 5/15 (33.3) |
Halved PPI (PP analysis) | 14/45 (31.1) | 14/45 (31.1) | 11/34 (32.3) | 9/24 (37.5) | 6/12 (50) |
Halved PPI (ITT analysis) | 14/50 (28) | 14/50 (28) | 11/42 (26.1) | 9/31 (29) | 6/15 (40) |
Unchanged PPI (PP analysis) | 6/45 (13.3) | 7/45 (15.6) | 9/34 (26.5) | 4/24 (16.7) | 1/12 (8.3) |
Unchanged PPI (ITT analysis) | 6/50 (12) | 6/50 (12) | 9/42 (21.4) | 4/31 (12.9) | 2/15 (13.3) |
Stopped or halved PPI (PP analysis) | 39/45 (86.7) | 38/45 (84.4) | 25/34 (73.5) | 20/24 (83.3) | 11/12 (91.7) |
Stopped or halved PPI (ITT analysis) | 39/50 (78) | 38/50 (76) | 25/42 (59.5) | 20/31 (64.5) | 11/15 (73.3) |
Key safety findings
Pneumothorax occurred in 3.9% (2/51) procedures; this was confirmed by X-ray immediately after the procedure and managed by immediate transthoracic drainage. Both patients had rapid resolution of the pneumothorax and were discharged from hospital within 3 days.
No persistent post-intervention side effects were reported.
Study 4 Bell (2021)
Study type | Case series |
|---|---|
Country | USA |
Recruitment period | 2008 to 2015 |
Study population and number | n=151 with GORD |
Age and sex | Median age 62 years (range 30-91), 42% male |
Patient selection criteria | Inclusion criteria: Patients ⩾18years of age who were able to provide informed consent and consented to TIF, and who had objective documentation of GORD. Exclusion criteria: Axial hernia height >2 cm; Los Angeles classification C or D oesophagitis; Barrett's oesophagus defined as visible columnar lined (⩾1cm) oesophagus demonstrating intestinal metaplasia on biopsy |
Technique | TIF was done under general anaesthesia with complete muscle relaxation using the EsophyX2 (Endogastric Solutions, Inc., Redmond, WA, USA) device and a modified version of the TIF 2.0 technique. |
Follow up | Median follow up 4.92 years (range 0.7 to 9.7 years) |
Conflict of interest/source of funding | Research support for data collection provided by EndoGastric Solutions, Inc., Redmond, WA, USA. |
Analysis
Follow up issues: Of the 151 patients who had TIF, 87% (131/151) were available for follow up. Five years or greater follow up was obtained on 51% (62) of the 120 total patients 5 years or more out from surgery (median follow up 6.8 years, range 5 to 9.7 years).
Study design issues: Single centre study analysis of prospectively collected data. The primary outcome measures were clinical response assessed by GORD-HRQL and regurgitation scores used in prior TIF studies, use of PPI, perioperative complications, and need for re-intervention.
Data were analysed using t tests for continuous data and Fisher's exact test for categorical data. A mixed effect model was used to assess the changes in treatment effect on quality-of-life measures (GORD-HRQL and regurgitation scores) in terms of testing mean differences, a p-value less than 0.05 was considered statistically significant. All mixed models were fitted in SAS software version 9.4 (SAS Institute, Inc., Cary, NC, USA). All other analyses were done using XLSTAT and JMP software.
Study population issues: The median BMI of participants was 26.6 (range 20-36.1) and the average duration of symptoms prior to TIF was 11.3 years (range 0.15–24.2). Daily PPI use prior to TIF was reported by 93% (140/151) of patients with 30% having taken 80mg/day. Seventy-eight per cent of patients reported moderate to severe ongoing GORD symptoms preoperatively despite PPI therapy. The median GORD-HQOL scores at baseline were 21 (IQR 9.5-39) off PPI and 14 (IQR 4-24) on PPI. Median regurgitation was 15 (8–20) off PPI and 11 (5–20) on PPI at baseline.
Other issues: Previous version of study also included in McCarty (2018) systematic review, but is it not possible to calculate the exact extent of overlap.
Key efficacy findings
Number of patients analysed: 151
22% (33/151) of TIF patients had laparoscopic revisional surgery at a median of 14.7 months after surgery. All revisions were accomplished without perioperative complication and long-term quality of life outcomes were equivalent to those patients who did not undergo reoperation.
Symptom changes and quality of life
Outcome | |
Median GORD HRQL at 4.92 years, all patients | 4 (IQR 2-8) |
Median GORD HRQL at 4.92 years, patients on PPI | 6 (IQR 3-16) |
Median GORD HRQL at 4.92 years, patients off PPI | 2 (IQR 0-7) |
Median GORD HRQL at 5-9 years | 5 (IQR 2-9) |
Successful (>50%) reductions in GORD-HRQL scores at 4.92 years | 64% |
Successful (>50%) reductions in GORD-HRQL scores in patients followed for >=5 years | 68% |
Median dysphagia (assessed by GORD HRQL) at 4.92 years (scored 0-10) | 0 (IQR 0-2), p<0.0001 compared with baseline of 2 (IQR 0-4) |
Median abdominal bloating (assessed by GORD HRQL) at 4.92 years (scored 0-5) | 1 (IQR 0-2), p<0.001 compared with baseline of 2 (IQR 0-4) |
Median regurgitation at 4.92 years | 0 (IQR 0-4) |
Median regurgitation at 5-9 years | 1 (IQR-0-3) |
Preservation of ability to vomit at 4.92 years (n=44) | 95% (42/44) |
Preservation of ability to belch at 4.92 years (n=44) | 90% (57/63) |
P value for GORD-HRQL score difference between patients on and off PPI therapy at 4.92 years follow up: p = 0.09.
GORD-HRQL by time points:
Time point | Estimated mean GORD-HQOL (SE) | Mean difference in GORD-HQOL compared with baseline (SE) | % of patients with >50% improvement in GORD-HRQL* | P-value for difference compared with baseline |
Baseline | 19.6 (0.9) | - | - | - |
1 year (n=75) | 7.5 (1.1) | –12.2 (1.3) | 72 | <0.0001 |
2 years (n=22) | 7.1 (1.9) | –12.5 (2.0) | 71 | <0.0001 |
3 years (n=24) | 9.7 (1.8) | –9.9 (1.9) | 75 | <0.0001 |
4 years (n=39) | 10.1 (1.7) | –9.6 (1.8) | 76 | <0.0001 |
5 years (n=35) | 6.4 (2.1) | –13.3 (2.2) | 77 | <0.0001 |
6 years (n=17) | 5.9 (2.2) | –13.7 (2.2) | 78 | <0.0001 |
7 years (n=11) | 3.5 (2.6) | –16.2 (2.7) | 83 | <0.0001 |
8 years (n=12) | 8.8 (2.7) | –10.8 (2.7) | 80 | <0.0001 |
9 years (n=13) | 6.1 (2.7) | –13.5 (2.7) | - | <0.0001 |
*Data estimated from bar charts
Pairwise comparison of HQRL:
Time point | Mean differences (SE) | p-value |
2 years versus 1 year | –0.4 (2.1) | 0.8640 |
3 years versus 2 years | 2.6 (2.5) | 0.3057 |
4 years versus 3 years | 0.4 (2.4) | 0.8762 |
5 years versus 4 years | –3.7 (2.7) | 0.1635 |
6 years versus 5 years | –0.4 (3.0) | 0.8862 |
7 years versus 6 years | –2.5 (3.4) | 0.4695 |
8 years versus 7 years | 5.3 (3.7) | 0.1542 |
9 years versus 8 years | –2.7 (3.7) | 0.4719 |
Regurgitation by time points:
Time point | Estimated mean (SE) | Mean differences (SE) | p-Value |
Baseline (ref) (n=103) | 13.7 (0.7) | - | - |
1 year (n=75) | 4.9 (0.8) | –8.8 (0.8) | <0.0001 |
2 years (n=22) | 4.4 (1.3) | –9.2 (1.3) | <0.0001 |
3 years (n=24) | 6.2 (1.2) | –7.4 (1.2) | <0.0001 |
4 years (n=39) | 5.4 (1.3) | –8.3 (1.3) | <0.0001 |
5 years (n=35) | 2.7 (0.7) | –11.0 (0.8) | <0.0001 |
6 years (n=17) | 3.0 (1.4) | –10.7 (1.4) | <0.0001 |
7 years (n=11) | 2.8 (1.7) | –10.9 (1.7) | <0.0001 |
8 years (n=12) | 3.1 (1.7) | –10.6 (1.7) | <0.0001 |
9 years (n=13) | 1.5 (1.7) | –12.2 (1.8) | <0.0001 |
Pairwise comparison of regurgitation:
Time point | Mean differences (SE) | P-value |
2 years versus 1 year | –0.4 (1.3) | 0.7557 |
3 years versus 2 years | 1.8 (1.6) | 0.2678 |
4 years versus 3 years | –0.8 (1.6) | 0.5987 |
5 years versus 4 years | –2.7 (1.4) | 0.0487 |
6 years versus 5 years | 0.2 (1.4) | 0.8641 |
7 years versus 6 years | –0.1 (2.1) | 0.9477 |
8 years versus 7 years | 0.2 (2.3) | 0.9199 |
9 years versus 8 years | –1.6 (2.4) | 0.5106 |
Medication usage
Time point | % of patients free of daily PPIs |
Baseline (n=151) | 7 |
0.5 years (n=94) | 73 |
1 year (n=83) | 72 |
2 years (n=78) | 71 |
3 years (n=73) | 68 |
4 years (n=65) | 69 |
5 years (n=53) | 67 |
6 years (n=42) | 69 |
7 years (n=27) | 74 |
8 years (n=18) | 78 |
*Values estimated from bar charts
Key safety findings
Complication | No. of patients | Comments |
|---|---|---|
2 | Patient 1: An immediate postoperative oesophagram demonstrating leak in patient with suspected oesophageal perforation led to suture repair of perforation, laparoscopic anterior fundoplication to cover the repair, and an uneventful postoperative course. Patient 2: Patient presented 7 days postoperatively with chest pain; CT scan was consistent with a mediastinal abscess oesophagram. Laparoscopic transhiatal drainage of the mediastinal abscess, takedown of the TIF, repair of oesophagus, and laparoscopic fundoplication resulted in an uneventful recovery | |
Vomiting | 1 | Elevated white blood cell count on postoperative day 1 – treated with antibiotics and recovered uneventfully |
Hypoxaemia | 1 | Patient with existing interstitial lung disease was hospitalised for 5 days |
Prolonged ileus | 1 | 3 days hospitalisation |
Study 5 Trad (2018)
Study type | RCT |
|---|---|
Country | USA |
Recruitment period | 2012 |
Study population and number | n=63 patients with GORD (n=40 TIF vs. n=23 PPI) |
Age and sex | Mean age 51.5 ± 10.3 years, 45% male |
Patient selection criteria | Inclusion criteria: Patients with chronic GORD and daily troublesome regurgitation and/or atypical symptoms refractory to PPI therapy; pathological oesophageal acid exposure confirmed by 48-hour pH monitoring off PPI therapy (percentage time pH <4 greater than 5.3%); and history of PPI use for at least 6 months. Exclusion criteria: Patients with hiatal hernia >2 cm; Hill grade III or IV; oesophagitis of grade C or D (Los Angeles classification); Barrett's oesophagus >2 cm; BMI greater than 35 kg/m2; oesophageal motility disorders; previous gastric or oesophageal surgery. |
Technique | Eligible patients were randomly assigned to receive either TIF 2.0 or maximum dose PPI therapy with a target allocation ratio of 2:1. After their 6-month evaluation, all patients in the PPI arm elected to undergo the TIF 2.0 procedure. All TIF 2.0 procedures were done using the EsophyX2 device (EndoGastric Solutions, Redmond, WA) under general endotracheal anaesthesia. |
Follow up | 5 years |
Conflict of interest/source of funding | Multiple authors report receipt of speaking honoraria from EndoGastric Solutions. Study funded by (EndoGastric Solutions, Redmond, WA). |
Analysis
Follow up issues: Of the randomised patients, 5% (3/63) were lost to follow up, 95% (60/63) completed 1 year follow up, 83% (52/63) completed the 3 year follow up and 70% (44/63) completed the 5-year follow up assessments.
Study design issues: Randomised multicentre open-label study with a crossover arm – patients in the PPI arm had TIF 2.0 6 months after initial randomisation.
Data were collected on elimination of troublesome symptoms, PPI use, reoperation, adverse events, and patient satisfaction. Troublesome symptoms were defined according to the Montreal consensus definition as mild symptoms occurring 2 or more days a week, or moderate to severe symptoms occurring more than 1 day a week.
Primary end points were elimination of troublesome regurgitation and elimination of all troublesome atypical symptoms at the 5-year follow up as evaluated by the RDQ (scored 0-24 with higher scores indicating greater severity) and Reflux Symptom Index (RSI; scored 0-45 with higher scores indicating greater severity).
Secondary endpoints were improvement in symptom scores (RDQ, RSI, GORD-HRQL), PPI use, reoperations, and satisfaction with current health condition. PPI use was self-reported by patients as complete cessation, occasional use (<3 days/wk.), or daily use rates. Patient satisfaction with their current health condition was reported as part of the GORD-HRQL (scored 0 to 50 with higher scores indicating greater severity), with 3 possible answers: satisfied, neutral, or dissatisfied.
Postoperative data at 1-, 3-, and 5-year intervals were compared with preoperative data using the repeated measures analysis of variance (ANOVA) followed by the post hoc Tukey-Kramer honestly significant difference multiple comparison procedure. In general, continuous variables were reported as means (SDs); categorical variables were reported as percentage, counts, and 95% CIs and were tested for significant difference using McNemar's test.
Patients who had a revisional procedure procedure) were included in the analyses and assigned the worst outcomes observed during the study from the timing of revisional surgery going forward. The statistical significance was prespecified by a p value of <0.05.
Study population issues: The mean BMI of the patient population was 28.5 ± 3.7, mean GORD symptom duration was 11.2 ± 9.8 years and mean PPI therapy duration was 8.6 ± 6.5 years. 1 patient had the short-segment variant of Barrett's oesophagus.
Other issues: Study also included in McCarty (2018) systematic review and Grossman (2021) systematic review as part of the HTA.
Key efficacy findings
Number of patients analysed: 60
5% (3/60) of TIF patients had revisional intervention (1 Dor fundoplication between 1 and 2 years, 1 LNF between 2 and 3 years and a second LNF between 3 and 5 years).
Changes in symptoms and quality of life
* =p<0.001 vs. screening
Medication usage
Clinical outcome | Baseline (n=60) | 1 year (n=60) | 3 years (n=52) | 5 years |
|---|---|---|---|---|
% of patients on daily PPI therapy -all patients | 100 (63/63) | 17 (10/60) | 27 (14/52) | 34 (15/44) (95% CI 22 to 49%) |
% of patients on occasional PPI therapy – all patients | - | - | - | 20 (9/44) (95% CI 11 to 35%) |
% complete cessation of PPI therapy – all patients | - | - | - | |
% of patients on daily PPI therapy – patients with elevated levels of distal oesophageal acid exposure at 3 years* | - | - | - | 21% (4/19) (95% CI 8 to 44%) |
% of patients on occasional PPI therapy –patients with elevated levels of distal oesophageal acid exposure at 3 years* | - | - | - | 16 (3/19) (95% CI 5 to 38%) |
% complete cessation of PPI therapy – patients with elevated levels of distal oesophageal acid exposure at 3 years* | - | - | - | 63 (12/19) |
* Defined as percentage total time of pH <4 greater than 5.3%, as measured by 48-hour pH testing
Key safety findings
No serious adverse events were reported, and no other complications associated with the TIF 2.0 procedure occurred in this study.
Study 6 Testoni (2022)
Study type | Case series |
|---|---|
Country | Italy |
Recruitment period | 2015 to 2019 |
Study population and number | n=46 patients with GORD |
Age and sex | Mean age 50 ±8 years, 54% male |
Patient selection criteria | Inclusion criteria: Patients aged 18 to 70 years inclusive; chronic (at least 6 months) GORD-related symptoms, both oesophageal and extra-oesophageal, with complete or partial response to PPI therapy; endoscopic findings of GORD or Barrett's oesophagus<3 cm); evidence of non-erosive reflux disease (NERD) or hypersensitive oesophagus at functional tests; body mass index<40 kg/m2; seeking an alternative to medical or surgical treatment; availability for a long-term follow up. Exclusion criteria: functional pyrosis; hiatal hernia ≥2.5 cm and non-reducible hernia (assessed through barium swallow contrast X-ray) as contraindication to TIF with MUSE device; Barrett's oesophagus ≥3 cm; malignant upper GI neoplasia; previous GI or thoracic surgery; (oesophageal varices, stenosis, or diverticula; portal hypertension; scleroderma; BMI >40 kg/m2; bleeding disorders; (j) age<18 years and>75 years; GORD symptoms for less than 6 months; inability to give consent; unavailability to long-term follow up. |
Technique | TIF was done using the Medigus Ultrasonic Surgical Endostapler (MUSE) device (Medigus, Omer, Israel) with patients under general anaesthesia. |
Follow up | 3 years |
Conflict of interest/source of funding | None. |
Analysis
Follow up issues: Two patients experienced post-procedural complications and 1 patient unresponsive to TIF were excluded from the follow-up analysis. Clinical follow up was available for 42 patients at 6 months and 1 year, 35 patients at 2 years, and 31 patients at 3 years. Follow up symptom assessment and endoscopy were done by physicians other than those who did TIF and who were unaware of the post-procedure outcomes.
Study design issues: Prospective single centre study that aimed to evaluate the effect of TIF done by a new-generation MUSE device. Primary endpoints were the percentage of patients who stopped or at least halved PPI consumption and the GORD-HRQL and RSI questionnaires scores (off-PPI), calculated both as median values and percentage of patients who experienced at least 50% reduction compared with before TIF. Secondary endpoints included safety outcomes, endoscopic findings assessing the presence and grade of oesophagitis, hiatal hernia and Hill's grade of the gastro-oesophageal valve compared with before TIF; HRM and 24-h pH-impedance findings compared with before TIF.
Statistical significance was assessed through separate paired samples two-tailed Wilcoxon signed-rank sum test. Both per protocol (PP set) and intention-to-treat (ITT set) analyses were done. The thresholds of statistical significance were adjusted for multiple comparisons; the threshold value was 0.0125 for clinical parameters and 0.01 for functional parameters
Study population issues: The mean BMI of patients was 24±3.2 and mean duration of symptoms was 9±6 years. 67.4% (31/46) of patients complained of both oesophageal and extra-oesophageal symptoms. 22/46 patients (47.8%) required double-standard dose PPI therapy and 19/46 patients (41.3%) required single-standard dose PPI to control symptoms, while 5/46 patients (10.9%) assumed PPIs at halved standard dose or occasionally. At pre-TIF upper G.I. endoscopy, 2/46 patients (4.3%) had Barrett's oesophagus without dysplasia and 30/46 patients (65.2%) had a diagnosis of non-erosive reflux oesophagitis, confirmed by pathological 24-h pH-impedance recording.
Key efficacy findings
Number of patients analysed: 46
Technical success and rate of reintervention
TIF by MUSE™ was technically feasible in 45/46 patients (97.8%). In 1 patient it was impossible to pass the MUSE™ device through the cervical oesophagus because of a compression due to protrusion of a cervical vertebra.
One patient was unresponsive to TIF and had Nissen fundoplication within 6 months after the procedure.
Medication usage
PPI therapy, N (%) | 6 months (PP, n=42) | 6 months (ITT, n=46) | 1 year (PP, n=42) | 1 year (ITT, n=46) | 2 years (PP, n=35) | 2 years (ITT, n=39) | 3 years (PP, n=31) | 3 years (ITT, n=35) |
Stopped | 27/42 (64.3%) | 27/46 (58.7%) | 27/42 (64.3%) | 27/46 (58.7%) | 22/35 (62.9%) | 22/39 (56.4%) | 23/31 (74.2%) | 23/35 (65.7%) |
Dose at least halved | 10/42 (23.8%) | 10/46 (21.7%) | 11/42 (26.2%) | 11/46 (23.9%) | 9/35 (25.7%) | 9/39 (23.1%) | 4/31 (12.9%) | 4/35 (11.4%) |
Stopped or dose at least halved | 37/42 (88.1%) | 37/46 (80.4%) | 38/42 (90.5%) | 38/46 (82.6%) | 31/35 (88.6%) | 31/39 (79.5%) | 27/31 (87.1%) | 27/35 (77.1%) |
Dose unchanged | 5/42 (11.9%) | 5/46 (10.9%) | 4/42 (9.5%) | 4/46 (8.7%) | 4/35 (11.4%) | 4/39 (10.2%) | 4/31 (12.9%) | 4/35 (11.4%) |
Symptom and quality of life changes
Baseline - patients completing 1-year follow up (n=42) | 6 months (n=42) | P value at 6 months vs. baseline | 1 year (n=42) | P value at 1 year vs. baseline | |
Median GORD-HRQL score (95% CI) | 22.0 (16.0–25.0) | 9.0 (6.0–12.0) | < 0.0001 | 7.0 (3.3–10.0) | 0.0001 |
Median RSI score (95% CI) | 19.0 (17.0–24.2) | 10.0 (3.0–12.0) | < 0.0001 | 5.5 (3.0–7.5) | 0.0001 |
Baseline -patients completing 2-year follow up (n=35) | 2 years (n=35) | P value at 2 years vs. baseline | Baseline - patients completing 3-year follow up (n=31) | 3 years (n=31) | P value at 3 years vs. baseline | |
Median GORD-HRQL score (95% CI) | 23.5 (16.0–26.8) | 8.5 (3.0–12.0) | 0.0007 | 24.0 (9.7–30.6) | 2.5 (0.47–8.7) | 0.007 |
Median RSI score (95% CI) | 17.0 (15.4–23.6) | 7.0 (3.4–8.6) | 0.0003 | 23.5 (17.0–25.5) | 6.0 (2.3–15.0) | 0.01 |
50% reduction of symptom score, n (%) | 6 months (PP, n=42) | 6 months (ITT, n=46) | 1 year (PP, n=42) | 1 year (ITT, n=46) | 2 years (PP, n=35) | 2 years (ITT, n=39) | 3 years (PP, n=31) | 3 years (ITT, n=35) |
GORD-HRQL score | 31/42 (73.8%) | 31/46 (67.4%) | 30/42 (71.5%) | 30/46 (65.2%) | 25/35 71.4%) | 25/39 (64.1%) | 21/31 67.7%) | 21/35 (60%) |
RSI score | 32/42 (76.2%) | 32/46 (69.6%) | 32/42 (76.2%) | 32/46 (69.6%) | 24/35 (68.6%) | 24/39 (61.5%) | 21/31 (67.7%) | 21/35 (60%) |
50% reduction of symptom score, n (%) | Baseline (n=46) | 6 months (PP, n=38) | 6 months (ITT, n=46) | 1 year (PP, n=31) | 1 year (ITT, n=46) |
Grade A oesophagitis | 14/46 (30.4) | 7/38 (18.4%) | 7/46 (15.2%) | 6/31 (19.3%) | 6/46 (13%) |
Recurrent hiatal hernia | 18/46 (39.1) | 2/38 (5.3%) | 2/46 (4.4%) | 2/31 (6.5%) | 2/46 (4.4%) |
Hill's grade I | 0 | 24/38 (63.2%) | 24/46 (52.2%) | 21/31 (67.7%) | 21/46 (45.7%) |
Hill's grade II | 40/46 (87) | 13/38 (34.2%) | 13/46 (28.3%) | 9/31 (29.0%) | 9/46 (19.6%) |
Hill's grade III | 6/46 (13) | 1/38 (2.6%) | 1/46 (2.2%) | 1/31 (3.3%) | 1/46 (2.2%) |
Functional parameter, median (95% CI) | Baseline – patients with 6-month follow up (n=31) | 6 months (n=31) | P value – 6 months vs. baseline | Baseline -patients with 1 year follow up | 1 year | P value – 1 year vs. baseline |
No. total refluxes | 57.0 (38.3 to 79.4) | 31.0 (24.5 to 54.1) | 0.0002 | 41.5 (27.5 to 76.8) | 40.5 (24.7 to 68.8) | 0.37 |
No. acid refluxes | 37.0 (24.5 to 54.2) | 24.0 (12.3 to 41.2) | 0.0002 | 31.5 (20.6 to 54.6) | 27.5 (13.4 to 46.6) | 0.15 |
No. weakly acid refluxes | 11.0 (7.0 to 22.9) | 8.5 (6.0 to 15.9) | 0.22 | 7.5 (4.8 to 14.0) | 10.0 (6.0 to 19.8) | 0.23 |
No. alkaline refluxes | 2.0 (1.0 to 3.4) | 1.5 (0.0 to 2.7) | 0.81 | 0.0 (0.0 to 1.5) | 1.5 (1.0 to 2.5) | 0.16 |
No. proximal refluxes | 26.0 (12.8 to 37.8) | 12.0 (5.8–20.3) | 0.002 | 18.5 (11.0 to 34.5) | 18.0 (7.2 to 30.5) | 0.31 |
Longest reflux (min) | 8.4 (3.6 to 11.9) | 6.2 (5.0–15.0) | 0.68 | 8.0 (3.4 to 11.0) | 5.0 (4.0 to 12.0) | 0.89 |
DeMeester score | 21.1 (12.0 to 32.8) | 20.0 (6.0 to 37.7) | 0.53 | 17.8 (6.7 to 35.5) | 16.4 (5.6 to 26.9) | 0.46 |
5.8 (1.5 to 8.3) | 3.8 (1.3–5.1) | 0.006 | 5.7 (3.2 to 7.1) | 4.2 (2.9 to 5.0) | 0.16 |
Key safety findings
Rate of complications
Complication | No. of patients | Comments |
|---|---|---|
Oesophageal perforation | 1 | Occurred 48h after TIF |
Gastric fundus perforation | 1 | Occurred 2 cm distally to the cardia as the consequence of an incorrect placement of stapler because of a difficult ultrasound-guided alignment. |
Epigastric pain | 3/45 (6.7%) |
Study 7 Kalapala (2022)
Study type | RCT |
|---|---|
Country | India |
Recruitment period | 2017 to 2019 |
Study population and number | n=70 patients with GORD (n=35 EFTP vs n=35 sham) |
Age and sex | EFTP group: Median age 35 years (IQR 29-41), 71% male Sham group: Median age 37 (IQR 29-45), 71% male |
Patient selection criteria | Inclusion criteria: Gastro-oesophageal flap valve grade I–III (Hill's classification); pathological oesophageal acid exposure (percentage time with oesophageal pH <4 in 24hours>4.2%); abnormal DeMeester score≥14.7 or total reflux episodes>73; lower oesophageal sphincter pressure (LESP) between 5 and 15mm Hg. Exclusion criteria: ASA physical status >II; previous oesophageal or gastric surgery; pregnancy; large hiatal hernia >3cm; Los Angeles grade C/D oesophagitis; para-oesophageal hernia; Barrett's oesophagus; presence of oesophageal dysmotility on HRM. |
Technique | Patients were allocated to either the EFTP or the sham group in a ratio of 1:1 using block randomisation. On the day of procedure, all the patients had the assigned intervention (EFTP or sham) under general anaesthesia and endotracheal intubation after overnight fasting. All EFTP procedures were done using the GORDx device. |
Follow up | 12 months |
Conflict of interest/source of funding | None |
Analysis
Follow up issues: After randomisation and allotted intervention, patients were followed up and asked to visit hospital at 3, 6 and 12 months. There were no protocol deviations and all patients in both groups completed 12-month follow up including per-protocol hospital visits and response to telephone calls.
Study design issues: Single centre randomised sham-controlled trial that aimed to determine the efficacy and safety of EFTP (GORD-X) in patients with PPI-dependent GORD. The primary endpoint of the study was defined as reduction of 50% or more in GORD-HRQL total score from baseline at 3 months.
Secondary end points of the study included improvement in GORD-HRQL total score (scored 0-75 with higher scores indicating greater severity), improvement in GORD symptom scores at 3, 6 and 12 months, PPI usage, and oesophageal acid exposure and reflux episodes on 24-hour pH impedance monitoring at 3 and 12 months. Total reflux episodes determined by impedance were classified as acidic (pH <4) and non-acidic (pH >4) based on pH monitoring.
Wilcoxon signed rank test and Friedman's two-way analysis of variance by ranks were used for comparing single pairs and multiple related samples, respectively. The PPI dependency rate between the EFTP and the sham groups after intervention was compared in a Kaplan-Meier analysis using log-rank test. Cox proportional hazards model was used to estimate the HR and 95% CIs. All tests of significance were two-tailed and a p value below 0.05 was considered statistically significant.
Study population issues: All patients were on PPI and the median (IQR) duration of PPI use was 2.5 (1.5–4.0) years. At the time of enrolment, 5/35 (14.2%) patients in the EFTP group and 3/35 (8.5%) in the sham group were on double dose PPI. The baseline demographics, endoscopic, manometric and reflux parameters did not differ significantly between the EFTP and the sham groups.
Other issues: If patients experienced reflux symptoms more than twice a week, PPI equivalent to 20mg rabeprazole or 40mg pantoprazole per day was prescribed over the phone and recorded. If the symptom control was inadequate at 4 weeks of starting PPI, the dose was doubled. Over the counter use of PPI was restricted but patients were allowed to use antacids on demand.
Key efficacy findings
Number of patients analysed: 70
Percentage of patients off PPI at 12 months: 62.8 % (22/35) in EFTP group and 11.4% (4/35) in sham group (p<0.001)
Estimated probability of PPI dependency in EFTP group at 12 months compared with sham (Kaplan-Meier): HR, 0.25; 95% CI 0.12 to 0.49; p<0.001
Parameter, median value (IQR) | EFTP | P value (EFTP compared with baseline) | Sham | P value (sham compared with baseline) | P value: EFTP vs. sham |
% time oesophageal pH <4 -Baseline | 4.4 (2.0 to 8.7) | - | 2.7 (1.3 to 5.9) | 0.127 | |
% time oesophageal pH <4 -3 months | 3.6 (0.4 to 9.0) | 0.422 | 3.5 (1.4 to 6.4) | 0.915 | 0.833 |
% time oesophageal pH <4 -12 months | 3.4 (0.6 to 5.5) | 0.276 | 5.4 (2.0 to 9.0) | 0.441 | 0.111 |
DeMeester Score – Baseline | 15.1 (7.6 to 28.0) | - | 12.2 (6.8 to 21.4) | - | 0.447 |
DeMeester Score – 3 months | 14.2 (1.7 to 29.3) | 0.447 | 14.7 (6.2 to 20) | 0.749 | 0.934 |
DeMeester Score – 12 months | 21.5 (11.0 to 49.2) | 0.231 | 20.1 (9.7 to 27.5) | 0.343 | 0.504 |
Total reflux episodes - Baseline | 90 (65 to 115) | - | 92 (65 to 130) | - | 0.733 |
Total reflux episodes – 3 months | 66 (46 to 92) | 0.005 | 85 (61 to 122) | 0.055 | 0.072 |
Total reflux episodes -12 months | 54.5 (33 to 100) | 0.122 | 120 (69.5 to 129) | 0.859 | 0.051 |
Acid reflux episodes - Baseline | 51 (33 to 73) | - | 40 (27 to 1) | - | 0.106 |
Acid reflux episodes – 3 months | 34 (16 to 63) | 0.063 | 40 (30 to 62) | 0.933 | 0.414 |
Acid reflux episodes -12 months | 31.5 (17.5 to 73.5) | 0.316 | 66 (47 to 69) | 0.260 | 0.227 |
Non-acid reflux episodes - Baseline | 34 (18 to 71) | - | 49 (25 to 77) | - | 0.264 |
Non-acid reflux episodes – 3 months | 23 (12 to 42) | 0.054 | 35 (21 to 70) | 0.077 | 0.048 |
Non-acid reflux episodes – 12 months | 11.5 (2.5 to 21.8) | 0.038 | 50 (25.5 to 62.5) | 0.214 | 0.005 |
Key safety findings
Rate of complications
Event | Frequency (ETFP) | Frequency (sham) | Length of hospital stay (days) | Severity |
Fever, moderate left sided pleural effusion | 1/35 (2.8%) | 0 | 5 | Moderate adverse event |
Left sided chest pain | 1/35 (2.8%) | 0 | 3 | Mild adverse event |
Left shoulder pain | 8/35 (22.8%) | 0 | 1 | Other incident* |
5/35 (14.2%) | 0 | 1 | Other incident* |
* Other incident – not classed as adverse event
Study 8 Chimikungara (2018)
Study type | Case series |
|---|---|
Country | USA |
Recruitment period | 2007 to 2014 |
Study population and number | N=57 patients with GORD |
Age and sex | Median age 46 years (IQR 37 to 59 years), 40% male |
Patient selection criteria | Inclusion criteria: Patients with GORD as confirmed by oesophagogastroduodenoscopy, barium swallow test, and 48-h pH monitoring. Exclusion criteria: absence of pathologic reflux; hiatal hernia greater than 2 cm; LA grade C or D erosive oesophagitis; biopsy proven Barrett's oesophagus |
Technique | Patients were placed in left lateral decubitus after undergoing general anaesthesia and TIF was done using the EsophyX device. |
Follow up | Short term follow up: median 12 months (IQR 11-18 months) Long term follow up: median 97 months (IQR 55-109 months) |
Conflict of interest/source of funding | None. |
Analysis
Follow-up issues: After 12 months, 63% (36/57) of patients were analysed; 14/57 were lost to follow up, 2 died from causes unrelated to the procedure, and 5 had LARS within 1 year of TIF. At long-term follow up (median 97 months), 23/57 (40%) of patients were analysed; a further 6/57 were lost to follow up, and a further 7 had LARS.
Study design issues: Single centre retrospective study aiming to evaluate the long-term impact of TIF on disease-specific quality of life and antisecretory medication use.
The primary outcome measure of this study was the GORD-HRQL assessment of disease-specific quality of life. Secondary outcome measures included PPI use and satisfaction with the procedure. Data were analysed using t tests for continuous data, Fischer's exact test for categorical data, and the Wilcoxon matched pairs test for non-parametric data. A p value less than 0.05 was considered statistically significant.
Study population issues: Mean BMI at baseline was 28.8 ± 4.9 kg/m2, and median GORD-HRQL score at baseline was 24 (IQR 15-28). The median DeMeester score was 30 (23–53). Twelve patients (21%) had endoscopic evidence of mild oesophagitis and twenty-six (46%) had endoscopic or radiographic evidence of a small hiatal hernia (1–2 cm). All patients were taking PPI therapy at least daily.
Other issues:
Key efficacy findings
Number of patients analysed: 57
During the study period, 21% (12/57) of patients had subsequent LARS (11 laparoscopic Nissen fundoplication and 1 laparoscopic magnetic gastro-oesophageal junction reinforcement) for recurrent GORD symptoms at a median interval of 24 (IQR 10–36) months after TIF. There were no statistically significant differences in patient demographics, hiatal hernia presence, oesophagitis, or DeMeester score between those who had subsequent anti-reflux surgery and those who did not.
Clinical outcome | Pre-op (n=57) | Short-term – median 12 months (n=36) | Long-term – median 97 months (n=23) |
|---|---|---|---|
Median GORD-HRQL score (IQR) | 24 (15-28) | 7 (2-18) (p<0.01) | 10 (6-14) (p<0.01) |
Percentage of patients with daily PPI use | 100 (57/57) | 53 (19/36) | 73 (16/23) |
Percentage of patients achieving PPI cessation | - | 47 (17/36) | 27 (6/23) |
Percentage dissatisfaction with GORD symptom management | 100 (57/57) | - | 26 (6/23) |
Key safety findings
None reported.
Study 9 Edriss (2014)
Study type | Case report |
|---|---|
Country | USA |
Recruitment period | Not reported |
Study population and number | n=1 |
Age and sex | 48 year old male |
Patient selection criteria | Not reported |
Technique | Patient had TIF using the EsophyX device system (EndoGastric Solutions). |
Follow up | Not reported |
Conflict of interest/source of funding | None. |
Analysis
Study design issues: This case report presented a case of TIF complicated by oesophageal perforation and developed mediastinitis, left pneumothorax, bilateral pleural effusions, and acute respiratory failure.
Key safety findings
The patient was diagnosed with GORD and hiatal hernia 15 years before presentation. His symptoms included chronic heartburn and night time cough that did not improve with lifestyle modification, histamine 2 blockers, and PPIs. Oesophageal 24-hour pH-impedance monitoring confirmed the diagnosis of GORD. He had TIF after failing conservative therapy.
A few hours after surgery, the patient developed midsternal chest pain. Physical examination revealed a mildly distressed state with rapid shallow breathing. His chest radiograph showed new small bilateral pleural effusions and bilateral lung opacities.
The next day, the patient had worsening chest pain, severe back pain, and shortness of breath. Physical examination revealed decreased breath sounds on the left side. The patient's respiratory status deteriorated, and he was intubated for mechanical ventilation. Another chest radiograph showed a large left-sided pleural effusion and bilateral pulmonary infiltrates consistent with consolidation and/or atelectasis.
Computed tomography of the chest showed moderate-to-large left-sided and moderate right-sided pleural effusions, a left-sided pneumothorax, and pneumomediastinum, findings consistent with distal oesophageal perforation. Computed tomography of the abdomen showed pneumoperitoneum.
The patient was started on vancomycin and ertapenem. A left-sided chest tube was inserted, and purulent, brown-greenish fluid was drained during the tube placement. Pleural fluid analysis showed an exudative effusion consistent with oesophageal perforation and empyema.
The patient had a fever for 5 days and leukocytosis despite the antibiotic coverage, chest tube placement, and nasogastric decompression. Blood cultures were negative on two occasions; pleural fluid cultures grew coagulase-negative Staphylococcus nitric oxide synthase and diphtheroids. On postoperative day 8, a left-sided thoracotomy and decortication for non-resolving empyema was done. The patient needed mechanical ventilation for 12 days and also developed acute renal injury.
At his most recent follow-up visit, the patient had been hospitalised at another hospital for 2 weeks because of the non-resolving right-sided empyema and had had right thoracotomy with decortication.
The distal oesophageal perforation and left-sided pneumothorax were attributed to injury during application of the polypropylene H-fasteners.
Study 10 Titus (2013)
Study type | Case report |
|---|---|
Country | USA |
Recruitment period | Not reported |
Study population and number | n=1 |
Age and sex | 42 year old female |
Patient selection criteria | Not reported |
Technique | Patient had endoscopic reduction of the hiatal hernia and TIF with use of the EsophyX device |
Follow up | 1 month |
Conflict of interest/source of funding | None. |
Analysis
Study design issues: This case report presented a case of a distal oesophageal perforation and oesophagopulmonary fistula after treatment for GORD with the EsophyX device
Key safety findings
The patient presented to an outside institution with intractable reflux. Upper endoscopy showed a small, reducible hiatal hernia with no evidence of oesophagitis or Barrett oesophagus. She subsequently had endoscopic reduction of the hiatal hernia and TIF with use of the EsophyX device and was admitted for overnight observation.
The next morning, she was noted to have a cough, low-grade fever, and weakness. A chest radiogram showed left posterior basilar infiltrate and a small pleural effusion presumed to be a left lower lobe aspiration pneumonia. Intravenous antibiotics were begun, and she was discharged 3 days later, having a full liquid diet and oral ciprofloxacin. She had multiple readmissions over the next 3 weeks for similar signs and symptoms with worsening severity until an oesophagram and computed tomography scan of the chest demonstrated distal oesophageal perforation with transmediastinal fistulous connection to a large cavitary left lung lesion. Blood cultures were positive for methicillin-sensitive Staphylococcus aureus.
Upon transfer to a different hospital the patient was in early septic shock. Her symptoms included shortness of breath and productive cough. Oesophagram confirmed the leak at 5 cm above the GEJ. Esophagogastroduodenoscopy showed an H-fastener in an area of inflamed distal oesophagus at the level of the suspected leak. No clear perforation was encountered. Inspection of the hiatus on retroflexion showed multiple H-fasteners in place, with the fundoplication no longer intact.
The left side of the chest was explored through a seventh-interspace thoracotomy. Dense inflammatory adhesions from the left lower lobe to the diaphragm were taken down. A fibrosed fistulous tract was encountered and appeared to have obliterated. Insufflation through an endoscope confirmed fistula closure. Wide debridement of the fistulous phlegmon was done. The distal end of the fistula terminated in the left lower lobe and led to a large parenchymal abscess cavity. The cavity was drained, debrided, and marsupialised. Four percutaneous drains were left within the thorax.
An oesophagram on postoperative day 4 showed no leak, and she had transition to oral antibiotics along with diet advancement. She was discharged on postoperative day 8 with a 4-week course of oral fluconazole, amoxicillin-clavulanate, and doxycycline. At 1-month follow up, she was tolerating soft foods with no further shortness of breath or cough, and no complaints of reflux.
Suspected cause of injury was an H-fastener placed too far proximally that had pulled through, lacerating the distal oesophagus.
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