Our next speaker will be Alayah Gutierrez. She's the Director of Endoscopy at Hopkins Sibley, where she's an assistant professor at Hopkins School of Medicine. She'll be talking about minimally invasive endoscopic and surgical treatments for reflux. Thank you, everybody, and thank you, the organizers, for the invitation. I am very excited to be here, and after we have listened to these great talks, now it's my turn to talk about endoscopic and surgical aspects of the management. So I have nothing to disclose, but I will be touching base on some of the label techniques that are available. So the first question will be why antireflux surgery for GERD? So Dr. Falk already went on to this, but those who are PPIs, why are we doing? Because PPIs are the first-line therapy for GERD. We know that, but however, up to 40% of the patients have incomplete response or partial response. There is increased recognition worldwide about potential adverse events of being on these medications long-term, and there is a lot of cost of medical therapy, around $80 billion of these prescription medications. Also like Dr. Demister says, the gastroesophageal reflux can be stopped by an effective surgery that is tailored to the individual physiologic defect. Then, who might be considered for alternative therapies to PPI? Those who are PPI-responsive but have persistent symptoms on daily BID, PPI, refractory GERD. Those who are intolerant to PPI, many potential adverse events, diarrhea, muscle cramps. Those who are PPI-adverse, they don't want to be on long-term PPIs, and these usually are young patients, postmenopausal women, chronic kidney disease patients. High-volume refluxers, those whose main symptom is regurgitation. Then, this group, GERD recurrence after antireflux surgery, it's also potential candidates for some endoscopic or redo surgical interventions. So the diagnosis before endoscopic or surgical therapy, I always use the GERD-related questionnaires, baseline and after any potential surgery. All patients, as we already saw, require an upper endoscopy, rule out EOE. We already heard our prior speakers talking about that. Most patients will require a pH monitoring, either the 24-hour pH impedance versus BRAVO. Particularly in our group, we already shifted to 96-hour pH monitoring, but as we said, off PPI, if it's baseline, the patient has never been tested before, and it's not needed if the patient has typical symptoms and the presence of great CD esophagitis, history of peptic stricture, or bariatric esophagus. High-resolution esophageal manometry, I would say I do it in all my reflux patients that will undergo any antireflux surgery, either endoscopic or surgical. Surgical, of course, endoscopically, because I want to make sure I'm not missing a major dysmotility disorder. Other tests, individualized, for example, varium swallow, very useful for our surgeons to complement the assessment of a hiatal hernia. Gastric end-team study, if the patient has bloating and nausea, to make sure this patient doesn't have gastroparesis before surgery. And thank you, Dr. Falk, for talking about heel grade. I cannot emphasize how important this is when choosing specifically potential endoscopic approaches. I'm not going to go over again, but certainly, heel 3 and 4, not candidate for endoscopic antireflux approaches, and these patients will get surgical antireflux approaches. So regarding endoscopic antireflux therapy, I divided them into radiofrequency ablation therapy, transoral fundoplication, mucosal resection and ablation, and endoscopic binding. The first two are the only FDA-available and approved options, endoscopically-wise. The others are off-label. Let's start with radiofrequency therapy. So this is really not endoscopic-guided. You are not having the scope in when you are actually doing the straight-up procedure. So you need to do an endoscopy, do your measurements, pass a savory wire, and then pass the catheter. So once you have passed your catheter, you advance the wire, you pass the catheter, you inflate the balloon, and then these four needles will get into the muscularis propria and will deliver low-power heat. Specifically to the lower esophageal sphincter and cardia. It's a non-stricturing approach. Decreases the compliance at the level of the lower esophageal sphincter and gastroesophageal junction by increasing the stiffness. Reduces postprandial transient lower esophageal sphincter relaxations. Decreases – there is the theory that can decrease the sensitivity to acid because it will affect the sensory neurons. The caveat effects may take months for the patient to actually feel it. This is taken from a paper, and as you can see, a patulus gastroesophageal junction. We typically recommend straight-up for heel-grade 1s. This is not a heel-grade 1, OK? But you can see the effect after treatment, and a thickened gastroesophageal flap valve after the therapy. Many, many, many data on strata out there, randomized control trials, prospective studies, and still data is mixed. For example, this is one of the most important last meta-analyses, including 2,400 patients, 28 studies, four of which are randomized control trials. There was symptom relief in 55% to 83% of the patients between one to three years. Improved GERD-related questionnaires, 72% at 10 years, 49% of PPI therapy at 10 years of therapy, reduced acid exposure, and there was no significant change in the lower sphincter vasopressor. The limitations, most of the studies did not have a control group. However, in 2015, there was this meta-analysis involving four randomized control trials with 165 patients that showed no difference between sham and strata. So again, larger randomized control trials are really needed to understand the benefit of this technique, and we are not recommending this routinely. Transoral fundoplication. In the United States, we only have the esophageal device TIF, what we call TIF. There are others in Europe, MUSE, GERDEX. So in these pictures, you can see the esophageal device that has had multiple, it has evolved over years. We currently have the Esophix Z Plus, and it will create gastroesophageal placations by deploying these H plastic fasteners to create serosa and serosa apposition, and the end goal is to create the 3-centimeter, 270-degree flat valve. This is a video. We can see a heel grade 1 patient, which is one. Heel grade 1 and 2 is the main category. Here you can see the device with a helical retractor where it purges the tissue from the gastroesophageal valve. We will pull the tissue and compress it with the tissue mold of the device. We will see these all tomorrow, and after we compress the tissue, we will wrap towards the greater curvature when we start on the posterior aspect, and then we repeat this on the anterior aspect and in the posterior at the level of the greater curvature. The final goal is to create this flat valve. Esophix, a lot of data as well, five randomized trials, three meta-analyses. It's mixed data because so far it has included all the different techniques. Right now we are on the 2.0 technique of TIF with the Esophix C plus device, and we don't have long-term data on this. But what we have there, better symptom control than PPI and SHAM, decreased number of reflux events. Like it was said before, the acid exposure time may or may not decrease. PPI use decreased but may increase over time, and this is also true for surgical fund applications. And we have learned that increasing the number of fasteners has shown to improve outcomes. The TEMPO trial is the longest data we have there with the TIF.2 technique, a little bit more homogeneous data, 86% elimination of regurgitation, 80% elimination of all atypical symptoms, 70% of patient satisfaction, GERD-related quality of life improved, 66% of patients were off PPI at five years but declined from 86% at three years of follow-up. There were three redo TIFs at five years with 7.5% of redo surgeries. Symptom of action of TIF, similar to Nissen fund application, both can reduce hernias less than two centimeters, repair hernia, elongate the intra-abdominal esophagus, both can create a fund application. Since 2017, combined with laparoscopic hernia repair, TIF has also closed that gap, and we can now do it in hiatal hernias greater than two centimeters. This is the new kid on the block, and this UCI Irvine group has actually published their multidisciplinary approach, minimally invasive surgeons and gastroenterologists doing a comitant hernia repair followed by TIF. So they published their work in 60 patients, all were symptomatic on PPI with hiatal hernias greater than two centimeters. At six and 12 months of follow-up, the scores, the GERD-related quality of life score significantly improved for heartburn and regurgitation. There was also decreased in the RSI for extra esophageal symptoms or LPR type of symptoms. There was significant decrease in the MR score and acid exposure times and significant decrease on PPI use. Only one intra-procedure adverse events during the TIF part, and it was still during the endoscopy. The first picture is the open cruda defect. The second picture shows the closed cruda defect, and the first endoscopic picture shows a heel gray four, then after the hernia repair before the TIF, and then after the TIF. Now let's talk about off-label potential techniques, mucosal resection and ablation. There have been a lot of different techniques published there. I chose the ones that have the best data. Antireflux mucosectomy or ARMS, it was first described by Dr. Inoue in 2014, and he recently published his experience. It consists of endoscopic mucosal resection, two-thirds to four-fifths of the cardiac circumference on retroflexion all the time, and the idea is to create scarring to improve all the outcomes. This included 109 patients. There was significant improvement in symptoms. Fifty percent of the patients were off PPIs. There was significant decrease in the MR score and the percentage of acid exposure time. Almost 15 percent of the patients came with dysphagia, required dilation up to three sessions, and this could be a potentially useful option in outer anatomy. This also was a good study, antireflux ablation therapy or ARAT, by one of our Spaniard colleagues. It consists of doing circumferential argon plasma coagulation below the G-junction, extending three centimeters into the cardiac and proximal stomach. This will create also scarring. You also will leave a spare area so you don't cause too much scarring, and this prospective study included 108 patients, 84 complete the full protocol. The median procedure time was 35 minutes, was pretty quick. No major adverse events, follow-up 3, 6, 12, 24, up to 36 months. There was significant improvement in symptoms, healed rate, improved pre-op esophagitis. At 36 months, almost 79 percent of the patients were off PPI. Seventy-two percent continued to have decreased acid exposure times less than 4 percent since the first follow-up, and almost 13 percent had dysphagia requiring dilation up to five sessions. This is something that is out there, Chinese group, they call this hiatal hernia endoscopic supernucosal dissection. You require a lot of expertise to do this, but it's out there. And it's similar to ARMS, but they will do endoscopic supernucosal resection of the hernia sac, and obviously the resection will depend on the hernia size, but here you can see a heel grade 4, and this is after the resection. Banding, nice study out there also, randomized controlled trials. They randomized 75 patients to endoscopic band ligation versus 75 control. They placed four bands at the level of the GE junction, four quadrants, and they followed them for a year. Most of the patients require only one session. They did pH monitoring every three months for a year, and there was significant increase in symptoms, 65 percent discontinued PPI. There was significant reflux episodes, a decrease in reflux episodes. They did not mention acid exposure time or the MRS score at all, for which I'm not sure if it's, you know, really helpful. And more or less 25 percent of the patients developed some degree of dysphagia, but did not require any treatment. Regarding the surgical antireflux therapy, briefly, we already know the options. I'm going to briefly mention laparoscopic fundoplication and magnetic sphincter augmentation. Laparoscopic fundoplication, Nissen fundoplication is the gold standard antireflux therapy. There are many types of fundoplication. Nissen is 360 degrees to PET 270 posterior fundoplication and DOR 180 anterior fundoplication, usually done after a Heller myotomy. To obtain optimal results, surgical treatment of gastroesophageal reflux should be tailored to the patient's anatomic and functional assessment. I believe a lot of our surgeons will follow this approach. Pros of both, most frequently used, the Nissen durability, superior reflux control, simpler, Tupe, less dysphagia, very esophageal clearance, easier to belch, vomit, not need for manometry. This is really, I would not send a patient to Tupe without a manometry. The cons of each, the Nissen is a hypercompetent valve. People will have at least transient dysphagia, inability to belch or vomit. They are going to have bloating. The Tupe, lower sphincter pressures, less competent barrier, high breakthrough incident, and shorter lifespan. There is a lot of randomized control trials between both. Obviously, Nissen will be more robust, but in terms of satisfaction and dysphagia, there is not much difference. So each surgeon will tailor the approach based on the patient's motility and conditions. There is a 20-year data by telephone surveys done by this group, 193 patients, 75% patients after 20 years were having no heartburn or any reflux symptoms, 20% symptoms less than one week, 6% will have both recurrence, and 43% were off PPI after 20 years. These beautiful trial in New England Journal of Medicine compared medical versus surgical therapy for refractory heartburn. Of 366 patients, only 78 were randomized, 27 to surgery, 25 to medical therapy that was omeprazole, baclofen, and neuromodulation, and 26 were controlled medical, only omeprazole and placebo. The primary outcome decreased in the amount of treatment success, which was defined as decrease of 50% or more of the GERD-related quality of life at 12 months, 67% of the surgical group achieved clinical success versus 28 active medical treatment and 12 controlled medical treatment. So the conclusion is for true refractory GERD to medical therapy, surgery is superior than medical therapy. Basic sphincter augmentation to finish, minimally invasive procedure, reproducible technique, minimally anatomic disruption, there is no gastric manipulation, so the theory is minimal side effects, mild lower sphincter reinforcement, not in hypercompetent valve, and it's permanent. It is a ring made of magnets embedded in titanium beads that placed above the G junction on resting pressure will be closed when the food bolus comes will open to allow the food to pass and then come back to the resting. This meta-analysis included 197 studies, only three met selection criteria, 688 patients, 270 Tunisian fund application versus magnetic sphincter augmentation, 415. The meta-analysis looked into a variety of outcomes. Magnetic sphincter augmentation was only significantly superior to Nissen in preventing patients' ability to belch and ability to emesis. The rest of the outcomes were non-significant. Limitations, there were no randomized controlled trials and there was short-term follow-up. So in conclusion, PPIs are the most cost-effective therapy for GERD symptom reduction, yet increased interest in other alternatives. Laparoscopic anti-reflux surgery continues to be the gold standard for refractory GERD with good safety profile when done by expert surgeons. Endoscopic therapies will not replace surgical fund application and therefore are used for in those patients with breakthrough symptoms on PPI such as regurgitation or those that are PPI averse. More research is needed to ensure best selection of therapy for the appropriate patients. Thank you very much.

Alayah Gutierrez

minimally invasive endoscopic

reflux

proton pump inhibitors

alternative therapies

surgical options