Gastric Pacing / Electrical Stimulation and Gastroesophageal Per Oral Endoscopic Myotomy
Number: 0678
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses gastric pacing / electrical stimulation and gastroesophageal per oral endoscopic myotomy.
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Medical Necessity
Aetna considers the following medically necessary:
- Gastric pacing (gastric pacemaker) and gastric electrical stimulation for the treatment of symptoms of nausea and vomiting from chronic gastroparesis, where the diagnosis is confirmed by gastric emptying scintigraphy, that is refractory/intolerant to dietary modification, 2 out of 3 classes of prokinetic medications (e.g., cisapride, domperidone, macrolide antibiotics, metoclopramide, and prucalopride) and 2 out of 3 anti-emetic medications (e.g., anticholinergics, antidopaminergics, antihistamines, phenothiazines, and serotonin 5-HT3 receptor antagonists) for at least 1 year;
- Revision or replacement of a previously approved gastric stimulator implant for complications associated with gastric pacing (e.g., bowel obstruction, gastric wall perforation, infection, lead dislodgement or lead erosion into the small intestine);
- Per-oral endoscopic myotomy (POEM) for the treatment of achalasia;
- Per-oral endoscopic myotomy for the treatment of Zenker diverticulum;
- Gastric per-oral endoscopic myotomy (G-POEM) for members with severe gastroparesis who meet all of the following criteria:
- Diagnosis of gastroparesis has been confirmed by a gastric emptying study (GES), where abnormal GES was defined as gastric retention greater than 60% at 2 hours and/or 10% at 4 hours after meal ingestion; and
- Symptom duration has been greater than 6 months; and
- Member has had an inadequate response to conservative treatment of gastroparesis, including dietary modification and a trial of at least one prokinetic agent (domperidone, metoclopramide, or erythromycin).
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Experimental, Investigational, or Unproven
Aetna considers the following procedures experimental, investigational, or unproven because the effectiveness of these approaches has not been established:
- Balloon dilation test for identification of candidates for gastric peroral endoscopic myotomy (G-POEM);
- Endoscopic functional luminal imaging probe (EndoFLIP) for prediction and evaluation of outcomes with G-POEM, and for prediction of clinical success before gastric peroral pyloromyotomy (G-POP);
- Gastric per-oral endoscopic myotomy (G-POEM) for treatment of congenital hypertrophic pyloric stenosis and all other indications (except for the one listed above);
- Per-oral endoscopic myotomy (POEM) for the treatment of non-achalasia spastic esophageal motility disorders;
- Temporary gastric electrical stimulation (GES) for the prediction of success of GES in the treatment of gastroparesis;
- Transcutaneous gastric pacing for gastro-intestinal motility recovery and inflammation improvement in individuals with early-stage acute pancreatitis;
- Gastric pacing and gastric electrical stimulation for all other indications including the following (not an all-inclusive list):
- As an initial treatment for gastroparesis
- For the treatment of autonomic nervous system disorders other than gastroparesis
- For the treatment of cyclic vomiting syndrome
- For the treatment of diabetes mellitus in persons without gastroparesis
- For the treatment of gastrointestinal dysmotility disorders other than gastroparesis
- For the treatment of obesity.
Note: The use of a second gastric electrical stimulator for the treatment of symptoms of nausea and vomiting from chronic gastroparesis is considered experimental, investigational, or unproven
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Related Policies
Background
Gastroparesis is a chronic gastric motility disorder of diabetic (both type 1 and type 2 diabetes) or idiopathic etiology. It is characterized by delayed gastric emptying of solid meals. Patients with gastroparesis exhibit bloating, distension, nausea, and/or vomiting. In severe and chronic cases, patients may suffer dehydration, poor nutritional status, and poor glycemic control (in diabetics). Although gastroparesis is often associated with diabetes, it is also found in chronic pseudo-obstruction, connective tissue disorders, Parkinson disease, and psychological pathology. Therapeutic options of gastroparesis include prokinetic agents such as metoclopramide, and anti-emetic agents such as metoclopramide, granisetron, or odansetron. Patients with severe gastroparesis may require enteral or total parenteral nutrition.
Gastric pacing (gastric stimulation) is utilized to treat individuals with chronic, intractable or drug-refractory nausea and vomiting secondary to gastroparesis. A gastric pacing system delivers electrical stimulation to the gastric muscles by means of two leads that are implanted directly into the stomach and connected to a generator that is implanted into the abdominal area. The device is regulated by an external programmer that noninvasively adjusts the level of gastric stimulation and also allows the device to be completely turned off at any time. Internal battery replacement is required every five to ten years.
Gastric pacing (gastric pacemaker) entails the use of a set of pacing wires attached to the stomach and an external electrical device that provides a low-frequency, high-energy stimulation to entrain the stomach at a rhythm of 3 cycles per minute. However, the gastric pacemaker is cumbersome and problematic for chronic use because of external leads.
Thus, a newer, implantable device (the Enterra Therapy System by Medtronic, Minneapolis, MN) was developed to provide gastric electrical stimulation (GES). Unlike gastric pacing, the Enterra delivers a high-frequency (12 cycles per minute), low-energy stimulation to the stomach. This stimulating frequency does not entrain the stomach, and therefore does not normalize gastric dysrhythmias; hence, the term GES is employed to differentiate between the Enterra and gastric pacing. The Enterra Therapy II system is the only gastric electrical stimulation system approved for marketing by the US Food and Drug Administration (FDA). It is approved under a Humanitarian Device Exemption (HDE).
The Enterra System was designed to treat intractable nausea and vomiting secondary to gastroparesis. Electrodes are implanted in the serosa of the stomach laparoscopically or during a laparotomy, and are connected to the pulse generator that is implanted in a subcutaneous pocket. The Enterra Therapy System (Medtronic, Minneapolis, MN) is currently the only GES that has received approval from the U.S. Food and Drug Administration (FDA). It was cleared by the FDA as a humanitarian use device. Thus, the manufacturer was not required to submit the level of evidence that would be required to support a pre-market approval application. The data presented to the FDA documenting the "probable benefit" of GES (Gastric Electrical Stimulation System) were based on a multi-center double-blind cross-over study (FDA, 2000), which included 33 patients with intractable idiopathic or diabetic gastroparesis. In the initial phase of the study, all patients underwent implantation of the stimulator and were randomly assigned to stimulation-ON or stimulation-OFF for the first month, with cross-over to OFF and ON during the second month. The baseline vomiting frequency was 47 episodes per month, which significantly declined in both ON and OFF groups to 23 to 29 episodes, respectively. However, there were no significant differences in the number of vomiting episodes between the two groups, suggesting a placebo effect. Thus, long-term results of GES must be validated in longer term randomized studies. It is important to note that GES did not return gastric emptying to normal in the majority of the treated-patients.
There exist preliminary data that suggested gastric pacing may be beneficial to patients with refractory gastroparesis. Forster et al. (2001) reported the findings of 25 patients who underwent gastric pacemaker placement. Both the severity and frequency of nausea and vomiting improved significantly at 3 months and improvements were sustained for 12 months. Gastric emptying time was also numerically faster over the 12-month period. Three of the devices were removed and 1 patient died of causes unrelated to the pacemaker 10 months post-operatively. The authors stated that after placement of the gastric pacemaker, patients rated significantly fewer symptoms and had a modest acceleration of gastric emptying.
Abell et al. (2002) performed GES in 33 patients with intractable gastroparesis. Patients were assessed 3, 5 and 12 months following permanent implantation. These researchers reported that 97% of patients experienced greater than 80% reduction in nausea and vomiting. For 24 patients who were followed for 1 year, the average weight gain was 5.5% and 9 of 14 patients receiving enteral or parenteral nutrition were able to discontinue it. The authors stated that while symptoms improved in the majority of patients following implantation of gastric stimulators, a properly randomized study is needed to ascertain the extent of a favorable placebo response.
- gastric electrical pacing,
- high-frequency GES, and
- sequential neural electrical stimulation.
The first method aims to reset a regular slow-wave rhythm, but is unable to re-establish efficient contractions and a normal gastric emptying. High-frequency GES, although inadequate to restore a normal gastric emptying, nevertheless strikingly improves the dyspeptic symptoms, such as nausea and vomiting, giving the patients a better quality of life and a more satisfactory nutritional status. The last method, neural electrical gastric stimulation, consists of a microprocessor-controlled sequential activation of a series of annular electrodes which encircle the distal 2/3 of the stomach and induce propagated contractions resulting in a forceful emptying of the gastric content. The latter method is the most promising, but it has so far only been tested in animals and would need to be tested in patients with gastroparesis before it can be used as a solution for this disease. All the afore-mentioned clinical studies, however, are not controlled and nearly all were published in abstract form. Thus, further controlled studies are needed to ascertain which of these techniques is more useful for the treatment of gastroparesis. This is in agreement with Rabine and Barnett (2001) who considered gastric pacing as an experimental technique for the management of patients with gastroparesis. Additionally, Smith and Ferris (2003) stated that gastric pacing offers promise for patients with medically refractory gastroparesis but awaits further investigation. Furthermore, in a systematic review of evidence of therapies for gastroparesis, Jones and Maganti (2003) concluded that gastric neuro-stimulation improves symptoms of nausea and vomiting, but therapeutic gain beyond placebo has not been demonstrated.
Abell et al. (2003) reported on a 2-phase clinical study of GES for gastroparesis: in the first phase, lasting 2 months, the investigators attempted to blind participants to stimulation. In the first phase, 33 patients with gastroparesis (17 diabetic, 16 idiopathic) were randomized to stimulation either ON or OFF for 1 month, then crossed-over to the other mode for 1 month. During the second uncontrolled phase of the study, all patients had their stimulator turned ON and were followed at 6 and 12 months. The investigators reported that, during the first phase of the study, vomiting frequency was significantly less in the ON position, than in the off position, with weekly vomiting frequencies of 6.8 and 13.5 episodes, respectively (p < 0.05). Total symptom score (mean sum of 6 symptoms, rated from 0 (absent) to 4 (severe) was also slightly less in the ON position than the OFF position, with scores of 12.5 + 1.0 and 13.9 + 1.1, respectively. The investigators noted that 21 patients preferred the ON mode and 7 patients preferred the OFF mode. An assessment by the National Institute for Clinical Excellence (NICE, 2004) commented that the results of this study are based on short-term follow-up of a small number of patients. The assessment noted that one of the difficulties in interpreting the evidence on this procedure in this and other studies is the reliance on self-reported measures of symptom relief. Furthermore, given the nature of the GES procedure, it is possible that patients experienced a placebo response. The investigators reported that, during the second phase, there were significant improvements from baseline in weekly vomiting frequency, total symptom score, and measures of gastric emptying. However, only 24 subjects included in this study were followed for 12 months, and gastric emptying data were available for only 20 subjects at 12 months.
More recent studies have examined the effectiveness of gastric pacing in refractory gastroparesis. These studies are limited by the lack of a control group, so that the effect of GES on gastroparesis can not be distinguished from the effects of the waxing and waning nature of these symptoms and the effects of concurrent interventions that the patient may be receiving for this condition. Lin et al. (2004) reported on the results of an uncontrolled study of GES in diabetic patients (n = 48) with refractory gastroparesis. The investigators reported that, after application of high-frequency GES by a permanently implanted system, improvements were observed in upper gastrointestinal symptoms, health-related quality of life, nutritional status, glucose control, and hospitalizations. van der Voort and colleagues (2005) reported improvements in symptom control and decreases in gastric retention (measured scintigraphically) after 12-months of continuous high-frequency/low-energy GES in a small group (n = 17) of insulin-dependent diabetic subjects suffering from drug-refractory gastroparesis. The lack of a control group limits the strength of conclusions that can be drawn from these studies.
MaCallum et al. (2005) reported on 12 month outcomes of GES in an uncontrolled study of a small group (n = 16) of subjects with post-surgical gastroparesis. The investigators reported that, after application of GES, there was significant improvement in upper gastrointestinal symptoms, quality of life, nutritional status, and hospitalization requirements. Lin et al. (2005) reported significant reductions in the use of prokinetic/anti-emetic medications and the need for hospitalization after application of GES in an uncontrolled study of refractory gastroparetic patients (n = 37). The authors also reported that subjects clinical and quality of life outcomes significantly improved after 1 year follow-up. Other long-term uncontrolled studies include those of Oubre et al. (2005) (46 month follow-up) and Cutts et al. (2005) (3 year follow-up).
An assessment by the National Institute for Clinical Excellence (2004) concluded that "[c]urrent evidence on the safety and efficacy of gastro-electrical stimulation for gastroparesis does not appear adequate to support the use of this procedure without special arrangements for consent and for audit or research". The assessment explained that “[c]urrent evidence on the efficacy of the procedure relates mainly to relief from nausea and vomiting, which occurs in some patients. There is little evidence that the procedure improves gastric emptying.” The assessment reported that one of the difficulties in interpreting the evidence on this procedure is that most studies lack a comparison group, and rely on self-reported measures of symptom relief.
Evidence-based guidelines on gastroparesis from the American Gastroenterological Association (Parkman et al., 2004) state: “Gastric electric stimulation is an emerging therapy for refractory gastroparesis …. Studies to better evaluate the efficacy of gastric electric stimulation are ongoing. As this type of treatment evolves, further delineation of the overall effectiveness, the type of patient who will likely respond, optimal electrode placement, and stimulus parameters should be explored.”
In a case series study, Filichia and Cendan (2008) assessed the response of transplant patients with gastroparesis to GES (Enterra therapy) and compared to non-transplant recipients. A questionnaire consisting of 11 questions was administered to investigate symptoms. Patients were asked to score these symptoms before and after surgery using a 0 to 5 Likert scale. A total of 13 consecutive patients underwent placement of the Enterra device with a mean follow-up of 12 +/- 6.1 months. Transplant recipients were as likely as diabetic or idiopathic patients to show improvements in symptoms of nausea, vomiting, as well as retching and prandial symptoms following Enterra therapy. In fact, transplant patients reported improvement in appetite and bloating symptoms more frequently than diabetics (p = 0.055 and p = 0.037, respectively). The authors concluded that post-transplantation gastroparesis responds to Enterra therapy as well as in patients with idiopathic or diabetic gastroparesis. They stated that Enterra therapy should be prospectively investigated in this population of patients.
Obesity is a major health problem among adults in the United States. It is also an increasing health concern among American children as well as adolescents. Various methods are employed in the management of obesity. One of the new approaches is gastric pacing, which is intended to induce early satiety through electrical stimulation of the gastric wall. However, the effectiveness of this technique in treating obesity has not been established. Buchwald and Buchwald (2002) considered gastric pacing as an experimental procedure for the management of morbid obesity.
An assessment of gastric pacing for obesity by the Swedish Council on Technology Assessment in Healthcare (SBU, 2004) found that "[t]here is insufficient scientific evidence on the short-term patient benefit of gastric pacing" for obesity, and that "[t]here is no scientific evidence on the long-term patient benefit of gastric pacing" for this indication. The assessment concluded:
“Gastric pacing is still an experimental method and should be used only in scientific studies that have been approved by a research ethics committee. Trials that include adequate control groups are very much needed.”
Yao et al. (2005) stated that acute retrograde gastric pacing at a tachygastrial frequency results in a significant reduction of water and food intake and a delay in gastric emptying without inducing any unacceptable symptoms. The investigators concluded that it is worthy to explore its therapeutic potential for obesity. In a review on the potential role of new therapies in modifying cardiovascular risk in over-weight patients with metabolic risk factors, Jensen (2006) noted that surgically implanted gastric pacemaker systems that modulate vagus nerve activity and delay gastric emptying are under study.
Salvi et al. (2009) reported their 2-year experience on gastric pacing in the treatment of morbid obesity. From August 2005 to January 2006, a total of 4 patients (mean age of 44 years) underwent placement for implantable gastric stimulation (IGS) therapy. The mean bone mass index (BMI) was 41.8, mean weight 117.2 kg. The IGS was activated 30 days after implantation. Fasting and post-prandial plasma ghrelin concentrations after a test meal were measured before and 1, 2, 3 and 6 months after implantation. All procedures were successfully completed laparoscopically. There were no major operative complications. Post-operative course was uneventful in all cases. One patient was lost to follow-up after 6 months. Post-operative lead dislodgement and cutaneous decubitus occurred in another patient, making necessary the removing of the device. For the remaining 2 patients, there was a significant weight loss (49 kg) in 1, while weight was unchanged in the other. Plasma ghrelin concentrations were not correlated among patients. The authors concluded that morbid obese patients can undergo IGS implantation by laparoscopy with minimal peri-operative complications. Attention to technical details is essential. In accordance with the manufacturer, these data demonstrated that gastric pacing is a safe procedure for selected patients supported by adequate psychological treatment, but outcome about weight loss should be evaluated among bigger trial. According to these investigators, their experience with IGS didn't provide satisfactory results, thus discouraging them to carry on with the study.
- the control group (stimulation off) or
- treatment group (stimulation on).
Patients were evaluated on a monthly basis. All individuals who enrolled in this study agreed to consume a diet with a 500-kcal/day deficit and to participate in monthly support group meetings. The procedure resulted in no deaths and a low complication rate. The primary endpoint of a difference in weight loss between the treatment and control groups was not met. The control group lost 11.7% +/- 16.9% of excess weight and the treatment group lost 11.8% +/- 17.6% (p = 0.717) according to an intent-to-treat analysis. The authors concluded that IGS as a surgical option for the treatment of morbid obesity is a less complex procedure than current bariatric operations. However, the results of the present study do not support its application. They stated that additional research is needed to understand the physiology and potential benefits of this therapy.
Policker and colleagues (2009) noted that the TANTALUS System (MetaCure Limited) is a minimally invasive implantable device for the treatment of type 2 diabetes (T2DM). The system detects food intake by sensing gastric electrical variations and applies electrical stimulation to the gut synchronized to natural gastric activity. It is commercially available in Europe and Israel and is in clinical trials in the United States. It has been tested in 132 patients worldwide to date. These researchers re-analyzed previously reported data from different studies. This retrospective analysis of the type 2 diabetes sub-population analyzed the expected benefit and characterized the significance of baseline A1c in the determination of the expected clinical outcome. From the total cohort of 132 patients implanted with the TANTALUS device in 10 different centers in Europe and the United States, these investigators identified 50 subjects (27 females, 23 males) who were obese with uncontrolled T2DM on a stable regime of oral medication for 3 months before implantation of the device. This population had similar inclusion/exclusion criteria as well as treatment protocols and were all treated for at least 24 weeks. The analysis was based on the A1c change compared to baseline. Data after 24 weeks demonstrated a reduction in A1c in 80% of the patients with average drop in A1c of 1.1 +/- 0.1%. The average weight loss was 5.5 +/- 0.7 kg. The authors concluded that these findings suggested that the TANTALUS stimulation regime can improve glucose levels and induce moderate weight loss in obese T2DM patients.
In an European multi-center, open-label clinical study, Bohdjalian and associates (2009) prospectively investigated the potential effect of the TANTALUS system on glycemic control and weight in over-weight subjects with T2DM. A total of 13 T2DM obese (7 females, 6 males, BMI of 37.2 +/- 1.0 kg/m(2), range of 30.4-44.0 kg/m(2)) subjects treated with oral anti-diabetic medications but with poor glycemic control (HbA1c greater than or equal to 7%, range of 7.3 to 9.5%) were implanted laparoscopically with the TANTALUS system. Thirteen subjects that had completed 3 months of treatment showed a significant reduction in HbA1c from 8.0 +/- 0.2% to 6.9 +/- 0.1% (p < 0.05), whereas fasting blood glucose decreased from 175 +/- 6 mg/dL to 127 +/- 8 mg/dL (p < 0.05). The glycemic improvement was accompanied by reduction in weight from 104.4 +/- 4.4 kg to 99.7 +/- 4.8 kg, and in waist circumference from 122.3 +/- 3.2 cm to 117.0 +/- 3.0 cm. The authors concluded that interim results with the TANTALUS system suggest that this stimulation regime can potentially improve glucose levels and induce moderate weight loss in obese T2DM subjects on oral anti-diabetic therapy with poor glycemic control. They stated that further evaluation is needed to ascertain if this effect is due to induced weight loss and/or due to direct signal-dependent mechanisms.
Thazhath et al. (2013) noted that delayed gastric emptying affects a substantial proportion of patients with long-standing diabetes, and when associated with symptoms and/or disordered glycemic control, affects quality of life adversely. Important clinic-pathological insights have recently been gained by the systematic analysis of gastric biopsies from patients with severe diabetic gastroparesis, which may stimulate the development of new therapies in the coming decade. The authors stated that experience with prokinetic therapies and treatments, such as pyloric botulinum toxin injection and GES, has established that relief of symptoms does not correlate closely with acceleration of delayed gastric emptying, and that well-designed randomized controlled trials are essential to determine the effectiveness of emerging therapies.
Cha and colleagues (2014) evaluated the current state-of-the-art of GES to treat obesity. These investigators performed systematic reviews of all studies to evaluate the effect of different types of GES on obesity. A total of 31 studies consisting of a total of 33 different trials were included in the systematic review for data analysis. Weight loss was achieved in most studies, especially during the first 12 months, but only very few studies had a follow-up period longer than 1 year. Among those that had a longer follow-up period, many were from the Transcend (Implantable Gastric Stimulation) device group and maintained significant weight loss. Other significant results included changes in appetite/satiety, gastric emptying rate, blood pressure and neuro-hormone levels or biochemical markers such as ghrelin and HbA1c. The authors concluded that GES holds great promises to be an effective obesity treatment. Moreover, they stated that stronger evidence is needed through more studies with a standardized way of carrying out trials and reporting outcomes, to determine the long-term effect of GES on obesity.
Gastric Pacing and Gastric Electrical Stimulation for Gastro-Intestinal Dysmotility
Sallam and associates (2014) stated that patients with gastro-intestinal (GI) dysmotility of systemic sclerosis (SSc, scleroderma) require careful evaluation and intervention. The lack of effective prokinetic drugs motivate researchers to search for alternative treatments. These researchers presented an overview of the pathophysiology of SSc GI dysmotility and the advances in its management, with particular focus on acupuncture-related modalities and innovative therapies. Original research articles were identified based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline methodology. These investigators have searched the MEDLINE database using Medical Subject Heading (MeSH) for all English and non-English articles with an English abstract from 2005 to October 2012. Key words used included gastric electrical stimulation. Only 4 original articles of various study designs were found studying complementary and alternative medicine (CAM) therapies for SSc patients. Despite the small patient study numbers, CAM treatments, acupressure, and transcutaneous electro-acupuncture, showed self-reported and physiologic evidence of improvement of GI functioning and/or symptoms in SSc patients. The authors concluded that CAM therapies include experimental modalities with the potential to offer relief of symptoms from GI dysmotility. They stated that larger studies are needed to investigate their optimal use in patient subsets to tailor therapies to patient needs.
Gastric Pacing and Gastric Electrical Stimulation for Cyclic Vomiting Syndrome
Grover and colleagues (2016) stated that cyclic vomiting syndrome (CVS) is a disabling migraine variant manifesting as severe episodes of nausea and vomiting and often refractory to many therapies. Gastric electrical stimulation, which can reduce nausea and vomiting in gastroparesis, may provide symptomatic relief for drug-refractory CVS. In a 1-year, non-randomized, clinical study, these researchers examined the effects of GES in reducing the symptoms of CVS and improving quality of life. A total of 11 consecutive patients with drug-refractory CVS based on Rome III criteria and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), underwent treatments with temporary GES (Temp GES) and permanent GES (Perm GES). Post-treatment follow-up was carried out up to 1 year after Perm GES therapy. Total symptom score decreased by 68% and 40% after Temp GES and Perm GES therapies, respectively. Hospital admission events significantly decreased to 1.50 (± 1.00) events from 9.14 (± 7.21) annual admissions prior to treatment with Perm GES. Vomiting episodes fell by 83% post-Temp GES, and 69% post-Perm GES treatments. Mucosal electrogram values also changed after temporary stimulation. The authors concluded that in a small group of drug-refractory CVS patients, treatments with Temp GES and Perm GES significantly reduced the severity of GI symptoms and frequency of hospital admissions. These preliminary findings need to be validated by well-designed studies.
Gastric Pacing and Gastric Electrical Stimulation for Autonomic Nervous System Disorders
Lee and Abd-Elsayed (2016) stated that neuromodulation (e.g., GES, cavernous nerve stimulation, deep brain stimulation, and vagus nerve stimulation) has been used with success in treating several functional disease conditions. The FDA has approved the use of neuromodulation for a few indications. These researchers discussed the evidence of using neuromodulation for treating some important disorders involving the autonomic nervous system (ANS) that are not currently FDA approved. This was a review article that included a systematic online web search for human clinical studies testing the effectiveness of neuromodulation in treating asthma, erectile dysfunction, gastroparesis, gastro-esophageal reflux disease (GERD), heart failure, and obesity. This review included all feasibility studies, non-randomized clinical trials, and randomized controlled trials (RCTs). The systematic literature search found 3, 4, 5, 4, 1, and 4 clinical studies relating to erectile dysfunction, gastroparesis, GERD, obesity, asthma, and heart failure, respectively. The authors concluded that this review article showed preliminary support based on clinical studies that neuromodulation can be of benefit for patients with important ANS disorders that are not currently approved by the FDA. They stated that all of these investigational uses are encouraging; further studies are needed for all indications discussed in this review before achieving FDA approval.
Gastric Pacing and Gastric Electrical Stimulation for the Treatment of Obesity
Morales-Conde and colleagues (2018) noted that weight regain following bariatric surgery is not uncommon. Safe, effective weight loss treatment up to 1 year has been reported with the closed-loop GES (CLGES) system. Continuous recording of eating and activity behavior by onboard sensors is one of the novel features of this closed-loop electrical stimulation therapy, and may provide improved long-term weight maintenance by enhancing aftercare. Four centers participating in a 12-month prospective multi-center randomized study monitored all implanted participants (n = 47) up to 24 months after laparoscopic implantation of a CLGES system. Weight loss, safety, quality of life (QOL), and cardiac risk factors were analyzed. Weight regain was limited in the 35 (74%) participants remaining enrolled at 24 months. Mean percent total body weight loss (%TBWL) changed by only 1.5% between 12 and 24 months, reported at 14.8% (95% confidence interval [CI]: 12.3 to 17.3) and 13.3% (95% CI: 10.7 to 15.8), respectively. The only serious device-/procedure-related adverse events (AEs) were 2 elective system replacements due to lead failure in the first 12 months, while improvements in QOL and cardiovascular risk factors were stable through 24 months. The authors concluded that during the 24 month follow-up, CLGES was shown to limit weight regain with strong safety outcomes, including no serious AEs in the 2nd year. These investigators hypothesized that CLGES and objective sensor-based behavior data combined to produce behavior change. The findings of this study support CLGES as a safe obesity treatment with potential for long-term health benefits.
Busetto and associates (2018) analyzed behavior changes using sensor-based food intake and activity data in participants treated with the CLGES system. Food intake and activity data (3-D accelerometer) were down-loaded at baseline and monthly/bimonthly for 12 months in a subset of patients with obesity (n = 45) participating in a multi-center trial with CLGES. Measured food intake parameters included the number of intakes during allowed and disallowed periods, night-time intakes, and between-meal snacks (average/day). Activity parameters included time in different levels of physical activity (mins/day), sleep/sedentary (hours/day), and estimated energy expenditure (EE). Weight loss at 12 months averaged 15.7 ± 7.7% of the baseline body weight. Stable reduction in the number of disallowed meals and between-meal snacks (p < 0.05), an increase in all levels of physical activity (p < 0.001), and an increase in activity-based EE (303 ± 53 kcal/day on average, p < 0.001) were observed. The authors concluded that significant and consistent positive changes in eating behavior and physical activity were observed in a small group of patients with severe obesity treated with CLGES therapy for 12 months. These lifestyle modifications led to a clinically significant 15% weight loss. There is an increasing interest today in the use of modern advanced technology in behavioral therapy. The potential of digital technology, including Web‐based tools, mobile phones and smartphone applications, virtual reality, and gaming technologies, has been reviewed in relation to both general obesity management and specifically in bariatric surgery. Electronic activity monitor systems have been increasingly studied and have yielded positive results in clinical practice. The CLGES system used in this study coupled effective and tailored GES with an extensive use of modern technology for behavioral self‐monitoring and modifications. They stated that this new form of a combined weight loss approach appears promising and warrants further testing and application.
The authors stated that this study had several drawbacks. First, food intake and physical activity down-loaded from the device at the 1st follow‐up visit, which was 2 weeks following implantation and before CLGES activation, were used as baseline data. This raised the possibility that the behavior of the patients in this period could be influenced by the recent surgery and not be representative of normal behavior before the surgery. However, device implantation required only minimal surgery, and patients usually did not experience significant problems or limitations in the early post-operative period. Second, the follow‐up in this study was limited to 12 months, and this short period of observation raised some concern regarding the durability of behavioral changes and weight loss. Weight loss has been reported to remain stable until 27 months in a small sample of patients treated with CLGES therapy, but controlled studies with a more extended follow‐up time are needed. These investigators stated that one of the major issues raised by this study was what part of the effect of the CLGES system was due to the electrical stimulation and what part was due to the behavioral modifications determined by data monitoring. The magnitude of the weight loss observed in this study was larger than the weight loss usually reported after behavioral programs, suggesting an additive effect between GES and behavioral modifications. However, the design of this study precluded definitive conclusion. The exact role played by each of the 2 components could be disentangled only by a specifically designed double‐blind study comparing weight loss in patients having the stimulation turned on or off.
Maisiyiti and Chen (2019) examined the feasibility of GES as a potential therapy for obesity. These investigators presented several GES methods for treating obesity and their effects on food intake and body weight. Possible mechanisms involved in the anti-obesity effect of GES were discussed. They provided comments on the potential of GES for obesity and expectations for future development of the GES therapy. The PubMed central data-base was searched from inception to May 2019. The literature search used the following terms: “Gastric electrical stimulation” combined with “obesity” and “Implantable gastric stimulation” and “pharmaceutical therapy” and “bariatric surgery”. The authors concluded that there is a potential to use GES for treating obesity. However, more efforts are needed to develop appropriate stimulation devices and to design an adequate therapy for treating obesity in humans.
In a multi-center, open prospective cohort, phase-1 clinical trial, Paulus and associates (2020) examined the safety of the Exilis GES system and determined if the settings can be adjusted for comfortable chronic use in subjects with morbid obesity. Gastric emptying and motility and meal intake were evaluated. A total of 20 morbidly obese subjects (17 female, mean BMI of 40.8 ± 0.7 kg/m2) were implanted with the Exilis system. Amplitude of the Exilis system was individually set during titration visits. Subjects underwent 2 blinded baseline test days (GES ON versus OFF), after which long-term, monthly follow-up continued for up to 52 weeks. The procedure was safe, and electrical stimulation was well-tolerated and comfortable in all subjects. No significant differences in gastric emptying half-time (203 ± 16 versus 212 ± 14 mins, p > 0.05), food intake (713 ± 68 versus 799 ± 69 kcal, p > 0.05), insulin area under the curve (AUC) (2,448 ± 347 versus 2,186 ± 204, p > 0.05), and glucose AUC (41 ± 2 versus 41 ± 2, p > 0.05) were found between GES ON and OFF. At week 4, 13, and 26, a significant (p < 0.01) reduction in weight loss was observed but not at week 52. At this time-point, the mean EWL was 14.2 ± 4.5%. The authors concluded that GES with the Exilis system can be considered as safe. No significant effect on food intake, gastric emptying, or gastric motility was observed. The reduction in weight loss with Exilis GES was significant but short-lasting. These researchers stated that further electrophysiological research is needed to gain more insight in optimal stimulation parameters and lead localization.
The authors stated that this study had several limitations. Due to the aims and deliverables of this study -- to assess safety and preliminary effectiveness of the Exilis system -- a control group was not included. In all studies and trials on interventions for weight loss, a control group is needed to fully evaluate efficacy. Several studies have shown between 12 and 14% of EWL in the control groups, which is comparable with what these investigators observed with the present study. Thus, they concluded that the additional effect of GES with the Exilis system with its current settings was limited. Up to now, substantial work with GES for the treatment of obesity has been performed, and results varied considerably. More essential basic research has to be carried out before this approach can be applied clinically. Pacing protocols should be optimized to achieve physiologically and clinically useful outcomes. Essential electrophysiological knowledge of the human stomach is still lacking, and more basic electrophysiological research work should be conducted before proceeding to new pacing protocols. Potentially, high resolution mapping of gastric slow-wave activity and the effects of gastric pacing on these waves may be a method to examine if pacing protocols will be effective. When optimal stimulation parameters have been assessed, these researchers recommended that they will be examined in a blinded, randomized, placebo-controlled trial.
Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Gastroparesis
Kristensen and colleagues (2014) performed a case-series study of 3 patients who underwent per-oral endoscopic myotomy (POEM) for nutcracker esophagus. At 3 months, 6 months and 1 year post-operatively, all patients had clinical follow-up, barium swallow and high-resolution manometry. All patients displayed marked improvement with a significant reduction in Eckardt score at follow-up after 1 year, from 10, 10 and 11 to 3, 1 and 1, respectively. During follow-up, the patients were diagnosed with increased reflux index and 1 patient was diagnosed with gastroparesis. The authors concluded that POEM may be considered as a therapeutic option for severe nutcracker esophagus; however, these researchers stated that further studies are needed.
Shlomovitz et al. (2015) reported that per-oral pyloromyotomy (POP) was performed in 7 women aged 33 to 65 years (mean of 51 years). All patients had a pre-operative work-up that included upper endoscopy, and a gastric emptying study. A pH study, and esophageal manometry were also performed when a concomitant fundoplication was considered. POP was technically successful in all 7 cases. There were no immediate procedural complications. Peri-operative, complications included: 1 patient with an upper GI bleed 2 weeks post-procedure, necessitating transfusions, and endoscopic clipping of a pyloric channel ulcer; 1 patient who experienced difficulty swallowing post-operatively, delaying discharge by 1 day; and 1 patient who developed a hospital-acquired pneumonia, delaying discharge by several days; 6 of the 7 patients experienced significant symptomatic improvement following the procedure. Three-month follow-up nuclear medicine solid-phase gastric emptying studies were available for 5 of the 7 patients. Normal gastric emptying at 4 hours was noted in 4 of 5 patients (80%); 1 patient did not respond to endoscopic management subsequently underwent an uneventful laparoscopic pyloroplasty, which also failed to significantly improve her symptoms. The authors concluded that POP was a technically safe and feasible endoscopic procedure; early follow-up suggested promising symptomatic improvement as well as objective improvement in gastric emptying. Moreover, these researchers stated that additional clinical experience is needed to establish the role of this technique in the management of gastroparesis.
Mekaroonkamol and co-workers (2016) stated that gastric POEM (G-POEM) is an emerging novel endoscopic technique as an incisionless pyloroplasty for refractory gastroparesis; and effective information of G-POEM on different types of gastroparesis is sparse. These researchers retrospectively evaluated cases of gastric POEM (G-POEM) in refractory gastroparesis. The G-POEM procedures were performed by a single expert endoscopist under a certain protocol. Gastroparesis Cardinal Symptoms Index (GCSI) and GES were evaluated before and after the procedure. Procedures related AEs were also recorded. All procedures were successfully completed without complications. Each case in this series was different in demography and etiology of gastroparesis, namely post-surgical, post-infectious, and idiopathic gastroparesis in an elderly men and 2 women. All cases were refractory to conventional treatment but demonstrated obvious success after G-POEM as a salvage therapy both clinically and on GES. The authors concluded that their cases revealed that G-POEM as a salvage therapy improved symptoms and gastric emptying in patients with different types of refractory gastroparesis; however, more data are needed to determine which subgroup of patients would benefit most from this novel procedure. This was a small (n = 3), retrospective study with heterogeneous types of gastroparesis.
Lebares and Swanstrom (2016) stated that a growing body of literature supports the use of laparoscopic pyloroplasty as a minimally invasive treatment of refractory gastroparesis that has failed conservative measures and for benign gastric outlet obstruction. Endoscopic pyloric dilation, stent placement, and Botox have been described for similar indications, but often with transient or mixed results. Per-oral pyloromyotomy (POP) has recently been proposed as an endoscopic alternative to surgical pyloroplasty or pylormyotomy because it is less invasive by its nature and potentially more durable than current endoscopic treatments.
Khashab et al. (2017) noted that gastric per-oral endoscopic myotomy (G-POEM) recently has been reported as minimally invasive therapy for gastroparesis. These investigators reported on the 1st multi-center experience with G-POEM and examined the safety and efficacy of this novel procedure for patients with gastroparesis with symptoms refractory to medical therapy. All patients with gastroparesis who underwent G-POEM at 5 medical centers were included. Procedures were performed following the same principles as esophageal POEM. Clinical response was defined as improvement in gastroparetic symptoms with absence of recurrent hospitalization. Adverse events (AEs) were graded according to the American Society for Gastrointestinal Endoscopy lexicon. A total of 30 patients with refractory gastroparesis (11 diabetic, 12 post-surgical, 7 idiopathic) underwent G-POEM. Previous therapies included botulinum toxin (Botox) injection in 12, transpyloric stenting in 3, and PEG with jejunal extension (PEGJ) in 1. Nausea/vomiting were the predominant symptoms in 25 patients. Weight loss was present in 27 patients with an average of 10% loss of body weight. G-POEM was completed successfully in all 30 (100%) patients with a mean procedure time of 72 mins (range of 35 to 223 mins). The mean myotomy length was 2.6 ± 2.3 cm. The mean length of hospital stay (LOS) was 3.3 days (range of 1 to 12 days); 2 AEs occurred in 2 (6.7%) patients, including 1 capno-peritoneum and 1 pre-pyloric ulcer, rated as mild and severe, respectively. Clinical response was observed in 26 (86%) patients during a median follow-up of 5.5 months; 4 patients (2 diabetic, 1 postsurgical, 1 idiopathic cause) did not respond to G-POEM. Repeat gastric emptying scan was obtained in 17 patients, normalized in 8 (47%), and improved in 6 (35%) patients. The authors concluded that G-POEM was a technically feasible procedure. The findings of this small, non-randomized study suggested the effectiveness of G-POEM for the treatment of patients with gastroparesis refractory to medical therapy. It concomitantly resulted in normalization of GES in a significant proportion of treated patients. This was a small (n = 30) study with heterogenous etiologies of gastroparesis (diabetic, idiopathic, and post-surgical), and a relatively short-term follow-up (median of 5.5 months). These preliminary findings need to be validated by well-designed studies.
Gonzalez and associates (2017) conducted a single-center, case-series study to examine G-POEM in refractory gastroparesis. These investigators evaluated 29 patients operated on between January 2014 and April 2016, with disturbed GES and/or elevated GCSI. The primary end-point was the efficacy at 3 and 6 months, based on GCSI and symptoms. The secondary end-points were GES evolution, procedure reproducibility and safety, and identification of predictive factors for success. The median follow-up was 10 ± 6.4 months. The clinical success rate was 79% at 3 months, 69% at 6 months, with a significant decrease in the mean GCSI compared to pre-operatively (3.3 ± 0.9 versus 1 ± 1.2 and 1.1 ± 0.9 respectively). The GES (n = 23) normalized in 70% of cases, with a significant improvement of the mean half emptying time and retention at 2 hours, and a discordance in 21% of the cases. In univariate analysis, diabetes and female gender were significantly associated with risk of failure, but not confirmed in multivariate analysis. Mid-term efficacy of G-POEM reached 70% at 6 months. The authors concluded that the procedure remained reproducible and safe, and that diabetes and female gender were predictive of failure.
Xu and colleagues (2018) noted that G-POEM has been regarded as a novel and minimally invasive therapy for refractory gastroparesis. In a retrospective, single-center study, these researchers reported the long-term outcomes and possible predictive factors for successful outcomes after G-POEM in an Asian population. This trial enrolled 16 patients (11 males and 5 females) who underwent G-POEM for refractory gastroparesis from August 2016 to October 2017. In addition, 13 patients had post-surgical gastroparesis, and 3 patients had diabetes. Subjects had severe and refractory gastroparesis, as indicated by a GCSI score of greater than or equal to 20, and evidence of a delay on GES. The primary outcome parameter was an assessment of the long-term clinical efficacy of the procedure. The secondary outcome parameter was the detection of possible predictive factors for success and the determination of cut-off values for such predictors. Technical success was achieved in 100% of the patients, with a mean procedure time of 45.25 ± 12.96 mins. The long-term clinical response was assessed in all patients during a median follow-up of 14.5 months. Clinical success was achieved in 13 (81.25%) patients. There was a significant reduction in the GCSI scores and GES values after the procedure compared to the baseline values, with p values of < 0.0001 and 0.012, respectively. Univariate regression analysis showed that the GCSI and gastric emptying scintigraphy had significant associations with the future clinical outcomes of the patients, but this finding was not confirmed in multivariate analysis. A GCSI cut-off score of less than or equal to 30 had a high sensitivity and a negative predictive value (NPV) of 100% for predicting a successful procedure; GES (half emptying time of less than or equal to 221.6 mins and 2-hour retention of less than or equal to 78.6%) had a high specificity and a positive predictive value (PPV) of 100%. The authors concluded that this study presented a promising long-term clinical outcome for G-POEM, with a high technical success rate and few AEs; GCSI score and GES values could be used as predictors of favorable outcomes. Moreover, these researchers stated that prospective, multi-center RCTs are needed to confirm these findings and determine the exact factors that predict patient responsiveness to G-POEM.
In a review on “Current and emerging therapeutic options for gastroparesis”, Myint et al. (2018) concluded that novel endoscopic therapeutic options such as G-POEM have shown some efficacy in small trials; further investigation is needed to identify new and effective therapeutic options.
Khoury and co-workers (2018) stated that gastroparesis significantly impacts a patient's life with limited and challenging treatments available. Although the pathogenesis is multi-factorial, pyloro-spasm is believed to have a major underlying role. Several therapeutic interventions directed to the pylorus have been developed over the past 10 years, including intra-pyloric injections of botulinum toxin (BTX), trans-pyloric stenting, and surgical pyloroplasty. All of these therapeutic options had limited and disappointing results. More recently, G-POEM has been reported as a treatment for refractory gastroparesis. In this review article, these investigators provided an overview on gastroparesis with a focus on the therapeutic interventions. In addition, they provided a literature summary and pool analysis of the clinical efficacy, scintigraphic efficacy, and safety profile of all studies that evaluated G-POEM in gastroparesis. A total of 7 studies have reported on the use of G-POEM in gastroparesis, and the pooled analysis of these studies showed a technical success of 100%, with clinical efficacy as assessed by the GCSI of 81.5%, GES normalization in approximately 55.5% of the cases, peri-operative complications in 7.6%, and intra-operative complications in 6.6%. The authors concluded that this suggested that G-POEM is a new promising therapeutic intervention for the treatment of gastroparesis with durable effect and limited potential AEs.
Kahaleh and associates (2018) stated that G-POEM has been offered as a novel therapy in the treatment of refractory gastroparesis. These researchers presented a multi-center case-series study of their experience with G-POEM. The severity of gastroparesis was assessed by delayed GES and an elevated GCSI. Patients then underwent G-POEM using the submucosal tunneling technique. The primary end-point was improvement in the GCSI score and improvement in gastric emptying on repeat scintigraphy. Secondary end-points were technical success, complication rate, procedure duration, and length of hospital stay (LOS) post-procedure. G-POEM was technically successful in all 33 patients. Symptomatic improvement was observed in 28/33 patients (85%), with a decrease in symptom score by GCSI from 3.3 to 0.8 at follow-up (p < 0.001). The mean procedure duration was 77.6 mins (37 to 255 mins). Mean GES improved significantly from 222.4 mins to 143.16 mins (p < 0.001). Complications were minimal and included bleeding (n = 1) and an ulcer (n = 1) treated conservatively. The mean LOS post-procedure was 5.4 days (1 to 14 days). The mean follow-up duration was 11.5 months (2 to 31 months). The authors concluded that G-POEM is a technically feasible, safe, and successful procedure for the treatment of refractory gastroparesis. Moreover, these researchers stated that a further comparative, multi-center study should be performed to compare this technique to laparoscopic pyloromyotomy.
Malik and co-workers (2018) reported their experience in performing G-POEM for refractory gastroparesis of different etiologies and determine symptom improvement. A total of 13 patients undergoing G-POEM were reported. Pre- and post-procedure GES and PAGI-SYM for symptom severity were obtained. Patients underwent G-POEM by creating a submucosal tunnel starting in the greater curvature of the distal antrum and extending it to the beginning of the duodenal bulb, followed by a full thickness pyloromyotomy. All 13 gastroparesis patients successfully underwent G-POEM (1 diabetic [DGp], 4 idiopathic [IGp], 8 post-surgical [PSGp]). Post-surgical patients included 4 s/p esophagectomy for esophageal cancer, 3 s/p Nissen fundoplication, and 1 s/p esophagectomy for achalasia. There were no procedure-related side effects. Of 11 patients completing follow-up questionnaires, 8 were improved subjectively (4 patients reported considerably better, 4 patients somewhat better, 1 unchanged, and 2 worse). Individual symptom severity scores tended to improve, particularly vomiting, retching, and loss of appetite. Of 6 patients that had post-G-POEM GES; GES improved in 4, unchanged in 1, and worsened in 1). The authors concluded that G-POEM for treatment of refractory gastroparesis appeared to be a feasible and safe technique that can be successfully performed in patients with a variety of etiologies including different types of post-surgical gastroparesis. The authors’ initial experience suggested that the majority of patients reported some improvement in symptoms, particularly symptoms of vomiting, retching, and loss of appetite. These researchers stated that further experience is needed to determine the safety and efficacy of G-POEM and predict those who best respond to this treatment.
Dacha et al. (2018) stated that POEM has emerged as a promising option for the treatment of achalasia. This study assessed POEM training process, outcomes, and improvement in QOL after POEM performed by an interventional endoscopist (mentor) with trainees. These researchers carried out a retrospective review of data for patients who underwent POEM with involvement of trainees. Trainees were trained in performing mucosotomy, submucosal dissection, creating submucosal tunnel, identifying gastro-esophageal junction, myotomy, and closure of mucosal incision in a step-by-step fashion. Trainees' performance on each step was evaluated by the mentor based on several key points in each step. The short form 36 (SF36) was obtained before and certain times after the primary POEM procedure was performed. A total of 62 patients, 26 men and 36 women with a mean age of 59 years, who underwent POEM were enrolled. A check-list included all related items for each step was established. All trainees obtained competence within 6 cases for each step; 61/62 (98.3%) patients had a significant improvement in the Eckardt's score post POEM: 9.3 ± 1.5 prior to POEM and 2.6 ± 1.2 after the POEM (p = 0.001) and a decrease in mean lower esophageal sphincter (LES) pressure: pre- and post-procedure mean LES pressures were 28.5 ± 11.4 and 12.1 ± 4.5 mmHg, respectively (p = 0.001). The SF-36 questionnaire demonstrated a significant improvement in QOL and comparable with those without trainees in other studies. The authors concluded that the findings of this preliminary study showed for the first time that training for POEM can be performed in a step-by-step fashion, learning mucosal incision, submucosal dissection, myotomy, and mucosal incision closure from an expert interventional endoscopist without increasing adverse events. The checklist for each step could be used as an important guide in training POEM. The outcomes of POEM in this study were similar to those reported by others without trainees. These researchers stated that further multi-center studies are needed to verify this training process and to establish a formal training protocol. This study described the findings of patients who underwent POEM for the treatment of achalasia with involvement of trainees.
Rodriguez et al. (2018) examined subjective and objective outcomes 12-weeks after POP at a high-volume center. The first 100 consecutive patients undergoing POP were included, with procedure dates between January 2016 and October 2017. Patients were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and 4-hour solid-phase scintigraphic gastric emptying studies (GES) prior to procedure and at 90 days post-POP. The study cohort was 85% women with a mean age of 45.0 ± 14.6 years. Gastroparesis etiologies were divided among idiopathic (56%), diabetic (21%), post-surgical (19%), and other in 4%. There were 67% of the patients who had previous endoscopic or surgical interventions for gastroparesis. Most POP procedures were performed in the operating room (97%) and were completed in an average of 33 mins; 10 patients incurred complications (10% ), which included 1 diagnostic laparoscopy and 2 cases of gastro-intestinal (GI) bleeding. Overall. GCSI improved from a pre-operative mean of 3.82 ± 0.86 to 2.54 ± 1.2 (p < 0.001). The improvement in each GCSI sub-score was also highly statistically significant. Among the patients with post-operative GES available, 78% had objectively better 4-hour emptying with a mean improvement in retention by 23.6% (p < 0.001). This included 57% of patients with normal gastric emptying post-POP. The authors concluded that for patients with medically refractory gastroparesis, POP resulted in both subjective and objective improvement in the majority of patients. Prior intervention did not obviate POP as a therapeutic option. These investigators stated that POP should be included along the treatment algorithm for patients with gastroparesis as an organ-sparing procedure.
Mekaroonkamol and colleagues (2019) noted that G-POEM is a novel procedure with promising potential for the treatment of gastroparesis but with limited data regarding predictors of clinical response. In a retrospective, longitudinal, single-center study, these researchers examined the safety and efficacy of the procedure and explored the impact of duration and etiology (diabetic versus non-diabetic) of gastroparesis on clinical outcome as measured by the GCSI. This trial was carried out at a tertiary care hospital over an 18-month period. A total of 40 patients with refractory gastroparesis (25 non-diabetic and 15 diabetic patients) were included; GCSI significantly improved throughout the study period (F (2.176, 17.405) = 10.152, p = 0.001). The nausea/vomiting subscale showed sustained improvement through 18 months (F (2.213, 17.704) = 15.863, p =< 0.00001). There was no significant improvement in bloating (F (2.099, 16.791) = 1.576, p = 0.236). Gastric scintigraphy retention was significantly reduced by 41.7% (t = -7.90; p < 0.00001). Multivariate linear regression modeling revealed a significant correlation between the duration of disease and a GCSI improvement at 12 months (p = 0.02), with a longer duration of disease being associated with a poorer long-term response. The etiology of gastroparesis was not associated with clinical improvement (p = 0.16); AEs (7.5%) included 1 capno-peritoneum, 1 peri-procedure COPD exacerbation, and 1 mucosotomy closure site disruption. The authors concluded that G-POEM appeared to be a safe and effective minimally invasive therapy for refractory gastroparesis, especially for patients with predominant nausea/vomiting and shorter duration of disease, regardless of the etiology. These researchers proposed the clinical criteria for undergoing G-POEM should be a GSCI of at least 2.0 and a gastric retention of greater than 20%. This was a relatively small (n = 40) retrospective study; its findings need to be further investigated.
Aghaie Meybodi and associates (2019) stated that G-POEM has been recently introduced as a minimally invasive approach for the treatment of refractory gastroparesis. These investigators carried out a meta-analysis to examine the feasibility and efficacy of this technique in the management of patients with refractory gastroparesis. PubMed, Embase, and Scopus databases were searched to identify relevant studies published through May 2018. Weighted pool rates (WPR) of the clinical resolution were calculated. Pooled values of GCSI before and after the procedure were compared. Pooled difference in means comparing gastric emptying before and after the procedure was calculated. Fixed or random effect model was used according to the level of heterogeneity. A total of 7 studies with 196 patients were included in the meta-analysis. The mean value of procedure duration was 69.7 (95% CI: 39 to 99 mins) and average estimate of LOS was 1.96 (95% CI: 1.22 to 2.95) days. The WPR for clinical success was 82% (95% CI: 74% to 87%, I2 = 0). Compared with pre-procedure GCSI values, mean values of GCSI were reduced significantly at 5 days (-1.57 (95% CI: -2.2 to -0.9), I2 = 80%) (p< 0.001). Mean values of gastric emptying were significantly decreased 2 to 3 months after the procedure (-22.3 (95% CI: -32.9 to - 11.6), I2 = 67%) (p < 0.05). The authors concluded that the findings of this meta-analysis suggested that G-POEM is an effective therapeutic intervention for management of patients with refractory gastroparesis in terms of clinical response and scintigraphic studies. Moreover, these researchers stated that large controlled trials are needed to identify the subset of patients who would benefit the most from this technique.
The authors stated that this study had several drawbacks. G-POEM is a relatively new technique and the studies that reported the outcome of this procedure have short follow-up duration. Thus, these researchers could not provide high-level evidence regarding the durability of this technique in offering long-term symptom relief. Furthermore, included studies were relatively small (7 studies with a total of 196 patients). Although these investigators did not observe a significant level of heterogeneity in their primary outcome measure, they noted a high level of heterogeneity in all of their secondary outcome measures. This finding could be attributed to different inclusion criteria in the studies. Included studies implemented distinct criteria to define clinical success rate. Moreover, patients with gastroparesis have various etiologies as well as symptoms and these researchers could not categorize their outcomes based on these etiologies, owing to small sample size of study populations and limited available data. For objective assessment of clinical response, GCSI was reported at baseline, 5 days, 1 month, and 3 months after the procedure and GES was evaluated at baseline and 2 to 3 months after the procedure. Finally, included studies have been performed by experienced endoscopists and this might affect the generalizability of these findings.
Tao and co-workers (2019) noted that G-POEM is a technically demanding endoscopic procedure. As of yet, there is no consensus on the technique. A variety of techniques have been reported in published studies. The essential technical steps of the procedure are establishment of submucosal tunnel in gastric antrum, identification of the pyloric muscular ring, selective circular myotomy, and a 2.5-cm to 3.0-cm length of myotomy. The authors stated that there are still some technical questions unanswered, and more studies are needed to establish standardized techniques and possible improvement of outcomes.
In a systematic review, Zhang et al. (2019) examined the safety and efficacy of G-POEM for the treatment of gastroparesis. PubMed, Embase, Cochrane Library and Web of Science databases were searched from their earliest records to May 2018. The evaluation of clinical efficacy and safety was based on gastric emptying scintigraphy normalization, the improvement in clinical symptoms and adverse event rate. R 3.5.0 software was used to calculate the pooled estimate rates by meta-analysis. The improvement rate of the Gastroparesis Cardinal Symptom Index score was analyzed at different follow-up times. A total of 14 studies (276 patients) were included in this systematic review. The pooled gastric emptying scintigraphy normalization rate was 61.3% (95% CI: 51.5 to 70.8%) and clinical symptom improvement rate was 88.2% (95% CI: 83.6 to 93.1%). Intra-operative complications were found in about 3.2% (95% CI: 0.1 to 4.2%) of all included patients, and post-operative AEs in 2.1% (95% CI: 0.3 to 4.8%). The mean Gastroparesis Cardinal Symptom Index score improvement rate was about 90.2% at 1-month follow-up, 83.3% at 3 months, 70.3% at 6months, 52.4% at 12 months and 57.1% at 18 months. The authors concluded that this systematic review demonstrated that G-POEM is a safe and effective treatment for gastroparesis. Moreover, these researchers stated that although the short-term outcomes are promising, prospective, randomized, controlled studies with large sample size and long-term follow-up are needed to further confirm these findings.
Shen and colleagues (2020) compared the long-term clinical outcomes of G-POEM versus GES in the treatment of patients with refractory gastroparesis. These investigators retrospectively evaluated 111 consecutive patients between January 2009 and August 2018. To overcome selection bias, they used propensity score matching (1:1) between G-POEM and GES treatment. The primary outcome was the duration of clinical response. After propensity score matching, 23 patients were included in each group. After a median follow-up of 27.7 months, G-POEM had a significantly better and longer clinical response than GES (hazard ratio [HR] for clinical recurrence 0.39, 95% CI: 0.16 to 0.95; p = 0.04). The median duration of response was 25.4 months (95% CI: 8.7 to 42.0) in the GES group and was not reached in the G-POEM group. The Kaplan-Meier estimate of 24-month clinical response rate was 76.6% with G-POEM versus 53.7% with GES. GES appeared to have little effect on idiopathic gastroparesis (HR for recurrence with G-POEM versus GES 0.35, 95% CI: 0.13 to 0.95; p = 0.05). The incidence of AEs was higher in the GES group (26.1% versus 4.3%; p = 0.10). The authors concluded that among patients with refractory gastroparesis, clinical response was better and lasted longer with G-POEM than with GES. The positive outcomes with G-POEM were likely to derive from the superior clinical response in patients with idiopathic gastroparesis. Moreover, these researchers stated that further studies are needed to confirm these findings.
Abdelfatah et al. (2020) noted that the prevalence of gastroparesis (GP) and resulting hospitalizations are increasing. Gastric peroral endoscopic pyloromyotomy (POP or G-POEM) is a novel technique in the treatment of refractory GP. Despite the initial promising results of GPOEM, 1/3 of patients do not exhibit any clinical response. Furthermore, loss of clinical response was reported in several studies. No response or loss of response after GPOEM may be related to inadequate myotomy. In a retrospective, case-controlled study, these researchers examined if double pyloromyotomy at G-POEM is superior to single pyloromyotomy. Because the follow-up time for the single myotomy group was much longer than that of the double myotomy group, these investigators matched the length of follow-up for the single myotomy group to that of the double myotomy group. The outcomes were measured by the changes in the Gastroparesis Cardinal Symptom Index (GCSI) before and 3 to 6 months after the procedure; AEs and other procedural and clinical parameters were also compared. A total of 90 patients underwent G-POEM (55 single and 35 double pyloromyotomy). The mean age was 47 ± 14 years, and the mean duration of symptoms was 5.3 ± 4.4 years. The average GCSI score was 3.8 before the GPOEM, and the average GCSI score 6 months after procedure was 1.8; 37 of 55 (67%) patients who underwent single pyloromyotomy achieved clinical response compared with 30 of 35 (86%) patients who underwent double pyloromyotomy. There were no significant differences for procedure time, post-operative pain, or LOS between the 2 groups. There was no difference in AEs in the 2 pyloromyotomy groups. The authors concluded that double pyloromyotomy was a safe and feasible technique during G-POEM. Clinical success was higher in patients undergoing double pyloromyotomy compared with single pyloromyotomy in this non-randomized, short-term follow-up study. These researchers stated that long-term studies are needed to further confirm these findings.
Mohan et al. (2020) stated that G-POEM is a novel minimally invasive technique in endo-surgery. Data are limited as to its efficacy, safety, and predictive factors. In a meta-analysis, these researchers examined the clinical outcomes of G-POEM and used the outcomes of surgical pyloroplasty as a comparator group in the treatment of refractory GP. They searched multiple data-bases from inception through March 2019 to identify studies that reported on G-POEM and pyloroplasty in gastroparesis. The primary outcome was to analyze and compare the pooled rates of clinical success, in terms of GCSI score and 4-hour gastric emptying study (GES) results, with G-POEM and pyloroplasty. A total of 332 and 375 patients underwent G-POEM (11 studies) and surgical pyloroplasty (7 studies), respectively. The pooled rate of clinical success, based on the GCSI score, with G-POEM was 75.8% (95% CI: 68.1 to 82.1, I2 = 50) and with surgical pyloroplasty was 77.3% (95% CI: 66.4 to 85.4, I2 = 0), with no significance, p = 0.81. The pooled rate of clinical success, based on the 4-hour GES results, with G-POEM was 85.1% (95% CI: 68.9 to 93.7, I2 = 74) and with surgical pyloroplasty was 84% (95% CI: 64.4 to 93.8, I2 = 81), with no significance, p = 0.91. The overall AEs were comparable. Based on meta-regression analysis, idiopathic gastroparesis, prior treatment with Botox and gastric stimulator appeared to predict clinical success with G-POEM. The authors concluded that G-POEM demonstrated clinical success in treating refractory gastroparesis. Idiopathic gastroparesis, prior treatment with Botox injections and gastric stimulator appeared to have positive predictive effects on the 4-hour GES results after G-POEM; outcomes appeared comparable to surgical pyloroplasty. The studies included for G-POEM were small (a total of 332 subjects in 11 studies).
In a systematic review and meta-analysis, Yan et al. (2020) examined the safety and efficacy of G-POEM for the treatment of refractory GP. PubMed, Embase and Cochrane databases were searched and used for study inclusion. Clinical studies since January 2013 to October 2019 were identified as suitable for inclusion. Conference papers, review articles, case reports, animal studies, letters, studies with repetitive data, studies that did not mention the GCSI score/GES hours or were not indicated in the standard form were excluded. GCSI score, GCSI reduction, gastric emptying scintigraphy at 4 hours (GES-4h) and GES time (GET) reduction were considered as major indexes and the meta-analysis was achieved using Review Manager 5.3. Research bias was measured according to Cochrane handbook. A total of 9 studies were included with a total of 235 patients that underwent G-POEM, and the technical success rate was 100%. After G-POEM, patients reported changes in GCSI score (6/9 studies, MD 1.41 [CI: 0.93 to 1.88], p < 0.0001), GCSI reduction (8/9 studies, odds ratio [OR] 3.00 [CI: 2.24 to 4.03], p < 0.0001), GES-4h (8/9 studies, MD 23.78 [CI: 19.88 to 27.68], p < 0.00001) and GET reduction (6/9 studies, OR 3.50 [CI: 2.12 to 5.78], p < 0.00001). The intra-procedure complication rate was 5.1% (12/235), including capno-peritoneum (7 cases) and accidental mucotomy (5 cases). The post-procedure complication rate was 6.8% (16/235), including abdominal pain (3 cases), bleeding (3 cases), ulcer (1 case), difficulty swallowing (1 case) and others (8 cases). Both per- and post-procedure complications were easily managed by conservative or endoscopic treatments. The authors concluded that the results showed that gastroparesis patients could benefit from G-POEM, the success rate was impressive and the complication rate was relatively low. However, caution is necessary when interpreting the results, primarily due to the limitations of uncontrolled studies. These researchers stated that randomized control trials (RCTs) are still needed for further evaluations.
Spadaccini et al. (2020) noted that GP is a chronic debilitating condition. Prior pyloric-targeted procedures are either invasive or have questionable efficacy; G-POEM has been proposed as a minimally invasive approach. These researchers performed a pooled analysis to evaluate the safety and efficacy of G-POEM for GP. Electronic data-bases (Medline, Scopus, Embase) were searched up to January 2019. Studies including patients who underwent G-POEM for GP were eligible. Procedural, clinical, and safety outcomes were assessed by pooling data with a random- or fixed-effect model according to the degree of heterogeneity to obtain a proportion with a 95% CI. A total of 10 studies were eligible for inclusion (292 patients), and 2 of the 10 studies were prospective; 7 studies were performed in the U.S, 2 in France, and 1 in China. Endoscopic pyloromyotomy was feasible in all patients. Significant symptomatic improvement was achieved after 83.9% of procedures (mean follow-up of 7.8 ± 5.5 months). When comparing the mean values of pre- and post-procedural scintigraphic evolution, there was a significant decrease of the residual percentage at 2 and 4 hours. The overall AEs rate was 6.8%. The authors concluded that G-POEM appeared to be a promising approach for GP in terms of safety and efficacy outcomes in the short-term.
Uemura et al. (2020) stated that G-POEM is a new therapeutic option for refractory GP. In a systematic review and meta-analysis, these researchers examined the effectiveness of G-POEM in refractory GP. For the quality of evidence, they used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. These investigators carried out a literature search using Medline, Embase, Cochrane library, LILACS and the Science citation index for studies related to G-POEM from the inception of its technique through January 2019. They selected studies that analyzed the GCSI and 4-hour solid-phase GES before and after the procedure to verify the efficacy of G-POEM, the main outcome measured. An analysis was performed using RevMan 5.3. A total of 10 studies comprising 281 patients were included in this systematic review. The pooled mean difference (MD) in GCSI following the procedure was 1.76 (95% confidence interval [CI]: 1.43 to 2.08], I2 = 72%). These researchers also performed GCSI subgroup analysis by follow-up duration that showed a pooled MD of 1.84 (95% CI: 1.57 to 2.12, I2 = 71%). The pooled MD in GES after the procedure was 26.28 (95% CI: 19.74 to 32.83, I2 = 87%), corresponding to a significant drop in percentage values of the gastric retention 4-hour scintigraphy. The authors concluded that the findings of this meta-analysis demonstrated that G-POEM is effective and showed promising outcomes in the clinical response and gastric emptying scintigraphy for gastroparesis’ and thus it should be considered in the management of refractory gastroparesis. Moreover, these researchers stated that there are only short- and mid-term efficacy studies; further controlled trials are needed to predict those who respond best to this treatment and to establish the long-term efficacy of this technique.
The authors stated that this meta-analysis is weakened by limitations inherent to meta-analyses and the included studies. Furthermore, most of the data were derived from observational studies, with all of them being of very low-quality evidence. G-POEM is a novel technique with promising outcomes. However, these investigators still cannot affirm for how long symptoms will remain improved, a situation likely to be explained, in part, by the short follow-up duration of the studies. The heterogeneity encountered in GCSI analysis was still high, even excluding the outlier study that presented a publication bias. However, all the studies showed a decrease in the values of GCSI and improved symptoms, indicating that the heterogeneity may be due to different population numbers (n = 7 to 100), baseline severity of the disease and follow-up periods (1 to 18 months) across each study and not to the effects. GES heterogeneity was also high, and all the studies improved GES as well. Finally, there were other limitations in the present study including its retrospective design and that the experienced endoscopists performed most of the procedures.
Usai-Satta et al. (2020) stated that over the last few years, some observational studies and case reports have shown promising results of G-POEM in the treatment of refractory GP; 7 studies with a total of 196 patients with refractory GP were included in a recent meta-analysis (Meybodi et al., 2019). The authors concluded that considerable efforts have been devoted in recent years to a better understanding of the pathophysiological mechanisms of GP; however, the results obtained so far are still unsatisfactory and further evidence is needed to fully understand the basic mechanisms of this disorder, in order to have better options for a more targeted and effective therapeutic approach.
Ragi et al. (2021) stated that data on the long-term outcomes of gastric peroral endoscopic myotomy (G-POEM) for refractory gastroparesis are lacking. In a retrospective, multi-center study, these investigators reported the findings of a large, multi-center, long-term follow-up study of G-POEM for refractory gastroparesis. This was a review of all G-POEM operations carried out in 7 expert French centers for refractory gastroparesis with at least 1 year of follow-up. The primary endpoint was the 1-year clinical success rate, defined as at least a 1-point improvement in the GCSI. A total of 76 patients were included (60.5% women; age of 56 years). The median symptom duration was 48 months. The median gastric retention at 4 hours (H4) before G-POEM was 45% (interquartile range [IQR] 29% to 67%). The median GCSI before G-POEM was 3.6 (IQR 2.8 to 4.0). Clinical success was achieved in 65.8% of the patients at 1 year, with a median rate of reduction in the GCSI score of 41%. In logistic regression analysis, only a high pre-operative GCSI satiety subscale score was predictive of clinical success (odds ratio [OR] 3.41, 95% CI: 1.01 to 11.54; p = 0.048), while a high rate of gastric retention at H4 was significantly associated with clinical failure (OR 0.97, 95% CI: 0.95 to 1.00; p = 0.03). The authors concluded that the findings of this study confirmed the efficacy of G-POEM for the treatment of refractory gastroparesis, as evidenced by a 65.8% clinical success rate at 1 year. Moreover, these researchers stated that although G-POEM is promising, prospective, sham-controlled trials are urgently needed to confirm its efficacy and identify the patient populations who will benefit most from this procedure.
Martinek et al. (2022) reported on a prospective, randomized controlled trial comparing G-POEM with a sham procedure in patients with severe gastroparesis. The primary outcome was the proportion of patients with treatment success (defined as a decrease in the Gastroparesis Cardinal Symptom Index (GCSI) by at least 50%) at 6 months. Patients randomized to the sham group with persistent symptoms were offered cross-over G-POEM. The enrolment was stopped after the interim analysis by the Data and Safety Monitoring Board prior to reaching the planned sample of 86 patients. A total of 41 patients (17 diabetic, 13 postsurgical, 11 idiopathic; 46% male) were randomized (21 G-POEM, 20-sham). Treatment success rate was 71% (95% CI 50 to 86) after G-POEM versus 22% (8–47) after sham (p=0.005). Treatment success in patients with diabetic, postsurgical and idiopathic gastroparesis was 89% (95% CI 56 to 98), 50% (18–82) and 67% (30–90) after G-POEM; the corresponding rates in the sham group were 17% (3–57), 29% (7–67) and 20% (3–67). Median gastric retention at 4 hours decreased from 22% (95% CI 17 to 31) to 12% (5–22) after G-POEM and did not change after sham: 26% (18–39) versus 24% (11–35). Twelve patients crossed over to G-POEM with 9 of them (75%) achieving treatment success. The investigators concluded that, in severe gastroparesis, G-POEM is superior to a sham procedure for improving both symptoms and gastric emptying 6 months after the procedure. The investigators explained that these results are not entirely conclusive in patients with idiopathic and postsurgical etiologies.
In a meta-analysis, Li et al. (2021) examined the feasibility and safety of G-POEM for gastroparesis. Relevant publications were identified through searching PubMed, Embase, Cochrane Library, and Web of Science before April 1, 2019. Studies presenting the clinical data of G-POEM for the treatment of GP were included. Data about safety and effectiveness were extracted, pooled, and analyzed. Forest plots were graphed based on random effects models. A total of 272 patients representing 8 studies were eligible for analysis. The pooled rates of GCSI at pre-procedure, 1-3 months, 6 months, and 12 months, were 3.25 (95% CI: 2.75 to 3.75), 1.80 (95% CI: 1.10 to 2.49), 1.56 (95% CI: 0.45 to 2.68), and 1.10 (95% CI: 0.75 to 1.45), respectively. The pooled results of 4-hour GES pre- and post-G-POEM were 41.89% (95% CI: 32.75 to 51.03%) and 16.48% (95% CI: 9.83 to 23.14%), respectively. Furthermore, the pooled clinical response rate was 84% (95% CI: 77 to 89%). The GES improvement rate and GES normal rate were also analyzed, and the results were 84% (95% CI: 77 to 90%) and 53% (95% CI: 39 to 66%), respectively. Finally, the pooled AE rate was 12% (95% CI: 6 to 19%). The authors concluded that G-POEM was shown to be feasible and safe for the treatment of GP with various etiologies, which could be a potential 1st-line therapy for certain patients. Moreover, these researchers stated that future studies are needed to examine the appropriate patients for G-POEM to explore the "most beneficial" subgroup of patients.
European Society for Gastrointestinal Endoscopy (Weusten, et al., 2020) states: "“ESGE recommends consideration of gastric peroral endoscopic myotomy (G-POEM) in carefully selected patients only, because it is an emerging procedure with limited data on effectiveness, safety, and durability. G-POEM should be performed in expert centers only, preferably in the context of a clinical trial. Strong recommendation, low quality of evidence, level of agreement 100%.”
Guidelines on gastroparesis from the American College of Gastroenterology (Camilleri, et al., 2022) state, regarding G-POEM, that "open-label studies suggest there is benefit in terms of symptom improvement and improved GE, although most studies were of only 3-6 months' duration. A 12-month study showed 56% patients improved at 1 year. Symptom control after endoscopic pyloromyotomy is comparable with surgical myotomy; however, endoscopic myotomy has been associated with fewer postprocedural complications and shorter length of hospital stay."
An American Gastroenterological Association clinical practice update on gastroparesis (Lacy, et al., 2022) states regarding G-POEM, that "[a]lthough technically feasible, randomized, sham-controlled studies do not exist, and long-term follow-up data are not available. Thus, although intriguing, G-POEM should not be considered first-line therapy and should only be performed at tertiary care centers using a team approach of experts (motility specialists, advanced endoscopists) with extensive experience in treating refractory gastroparesis patients."
Gastric Peroral Endoscopic Myotomy for the Treatment of Congenital Hypertrophic Pyloric Stenosis
Kozlov and colleagues (2019) noted that traditionally, a laparoscopic approach is used for treatment of congenital hypertrophic pyloric stenosis (CHPS) in newborns and infants. The novel technique, G-POEM, had been proposed as an alternative method. In this study, these researchers demonstrated for the first time the performance of G-POEM in an infant and its short-term results. G-POEM was performed in the Center of Newborn Surgery in Irkutsk (Russia) in August 2018 for a 1-month old infant, whose weight was 4,200 g. The patient had vomiting for 5 days before admission and a slight deficiency of body weight. The diagnosis of CHPS was confirmed by ultrasound (US) examination of the abdominal cavity. The pyloric muscle thickness was 7 mm. The operative technique of the performed G-POEM was performed by creation of a submucosal tunnel with a distance of 4 cm toward the pylorus and dissection of the hypertrophied muscle layer in a form of the Ramstedt's incision by using an electrocautery knife. At the end of the procedure, the mucosal membrane incision was closed by special clamps. The operating time was 65 mins. There were no intra-operative complications such as bleeding and/or mucosal perforation. The patient began to eat 6 hours after the procedure. The transition time to full enteral nutrition was 24 hours. The infant was discharged from the hospital the next day in good condition. These investigators did not observe early or late post-operative complications such as recurrence of pyloric stenosis and incomplete myotomy during post-operative observation. There were not even minimal scars on the patient's body. The authors concluded that G-POEM is a technically feasible, safe, and successful procedure for treatment of CHPS in newborns and infants. Moreover, these investigators stated that an additional study is needed to perform the comparison between this technique and laparoscopic pyloromyotomy.
Diverticular Peroral Endoscopic Myotomy (D-POEM) for the Treatment of Esophageal Diverticulum
In a retrospective, international, multi-center study, Yang and associates (2019) reported their experience with the diverticular peroral endoscopic myotomy (D-POEM) technique in the management of esophageal diverticula; D-POEM was carried out using the principles of submucosal endoscopy. A total of 11 patients with an esophageal diverticulum (Zenker's 7, mid-esophagus 1, epiphrenic 3) were included. The mean size of the esophageal diverticula was 34.5 mm. The overall technical success rate of D-POEM was 90.9%, with a mean procedure time of 63.2 mins, and there were no AEs. Clinical success was achieved in 100% (10 /10), with a decrease in mean dysphagia score from 2.7 to 0.1 (p < 0.001) during a median follow-up of 145 days (interquartile range [IQR] of 126 to 273). The authors concluded that endoscopic management of esophageal diverticula using the novel technique of D-POEM appeared promising. This 1st case-series study on D-POEM suggested that the procedure was feasible, safe, and effective in the management of esophageal diverticula; D-POEM offered the distinct advantage of ensuring a complete septotomy. Moreover, these investigators stated that larger studies are needed to confirm these preliminary findings.
Maydeo and co-workers (2019) noted that submucosal tunneling diverticular septotomy by D-POEM has emerged as an alternative to surgery for symptomatic esophageal diverticula, however, its medium- to long-term outcomes are currently unexplored. In this study, D-POEM for patients with symptomatic esophageal diverticula was prospectively studied to examine its safety and the 12-month outcomes. A total of 25 patients (72% men; median age of 61 years [range of 48 to 88]) with a Zenker's diverticulum (n = 20) or epiphrenic diverticulum (n = 5) were included. Major indications were dysphagia, recurrent broncho-aspiration, and foreign body sensation in 20 patients (80%), with a mean symptom duration of 2.5 years (range of 1 to 4). Complete submucosal tunneling septotomy was achieved in a mean of 36 mins (range of 25 to 45), with 100% technical success. The median hospitalization was 5 days (range of 4 to 10). The mean (standard deviation) Eckardt Score improved significantly from 13.2 (1.0) at baseline to 3.2 (1.4) at 12 months (p < 0.001) with clinical success in 19/22 patients (86%) and no long-term AEs. The authors concluded that D-POEM appeared safe and durable in patients with esophageal diverticula. Moreover, these researchers stated that further multi-center studies with a larger patient cohort are needed.
Sato et al. (2019) stated that esophageal diverticula are rare conditions that cause esophageal symptoms, such as dysphagia, regurgitation, and chest pain. They are classified according to their location and characteristic pathophysiology into 3 types: epiphrenic diverticulum, Zenker's diverticulum, and Rokitansky diverticulum. The former 2 disorders take the form of protrusions, and symptomatic cases require interventional treatment. However, the esophageal anatomy presents distinct challenges to surgical resection of the diverticulum, especially when it is located closer to the oral orifice. Since the condition itself is not malignant, minimally invasive endoscopic approaches have been developed with a focus on alleviation of symptoms. Several types of endoscopic devices and techniques are currently employed, including POEM. However, the use of minimally invasive endoscopic approaches, like POEM, has allowed the development of new disorder called iatrogenic esophageal diverticula. Furthermore, these investigators stated that no RCTs comparing the difference between endoscopic treatment and surgery, or among the different endoscopic techniques have been performed. Also, such studies of long-term follow-up results, including esophageal motility outcomes, are needed to decide the best intervention modality for esophageal diverticulum. Another issue is the risk of esophageal carcinoma in the remnant diverticulum. Although the absolute risk of esophageal carcinoma is rather low, surveillance endoscopy is necessary after treatment.
Zeng and colleagues (2020) noted that with the development of minimally invasive endoscopic approaches for the esophagus in recent years, POEM in the treatment of esophageal diverticulum has been described recently in some reports due to its successful outcomes. In a retrospective study, these researchers described their experience with the use of D-POEM in the management of esophageal diverticulum. This trial included consecutive patients with symptomatic esophageal diverticulum who visited the authors’ endoscopy center between April 2014 and January 2019. D-POEM was carried out based on the principles of submucosal endoscopy. A new symptomatic scoring system was introduced to evaluate the severity of diverticular symptoms. A total of 10 patients with esophageal diverticulum (Zenker's 2, mid-esophagus 5, and epiphrenic 3) were included. The overall technical success rate of D-POEM was 100%, with a mean procedure time of 38.9 ± 20.5 (range of 16 to 70) mins. No serious complications occurred. Clinical improvement was achieved in 90% (9/10) of patients. The symptomatic score was significantly decreased from 2.5 (IQR of 2.00 to 3.25) to 1.0 (IQR of 0 to 1.25) (p = 0.007) during a median follow-up period of 11.0 (IQR of 10.25 to 17.25) months. The authors concluded that the findings of this study suggested complete septotomy by D-POEM. Moreover, these researchers stated that these preliminary results and experience put forwarded D-POEM as a safe and effective technique for esophageal diverticulum.
Zenker POEM (Z-POEM) Diverticulotomy for Closing Defect due to Zenker's Diverticulum
Feußner et al. (2017) noted that esophageal diverticula are comparatively rare. The majority are Zenker's diverticula (ZD) but para-bronchial and epiphrenic diverticula can also occur. Para-bronchial diverticula are of low clinical relevance, whereas Zenker's and epiphrenic diverticula both belong to the group of pulsion diverticula and can become clinically apparent by dysphagia and regurgitation. Approximately 100 years after the first surgical treatment, peroral approaches (e.g. stapler dissection and flexible endoscopic diverticulotomy) have now achieved a certain level of importance. Both approaches are less invasive than the open approach but are evidently more prone to recurrences. Accordingly, traditional open diverticulectomy with cervical myotomy should be recommended to patients with a reasonable life expectancy and an acceptable operative risk. This holds particularly true for Brombart stages I to III of the disease, as complete myotomy cannot be achieved via the peroral access. The classical surgical treatment of epiphrenic diverticula is open or laparoscopic / thoracoscopic diverticulectomy with distal myotomy, mostly combined with an anterior partial fundoplication; however, the leakage rate is high and several alternative options are currently being evaluated.
Stasek et al. (2020) stated that esophageal diverticula represent a relatively rare pathology of the esophagus requiring a specific diagnostic and therapeutic approach . Interventional therapy is indicated for symptomatic diverticula, diverticula with other pathologies (tumor in the diverticulum, gastro-esophageal reflux disease [GERD], low-malignancy GE junction tumors). The open surgical approach is being increasingly replaced by minimally invasive surgical, endoscopic and combined methods. Surgical mini-invasive methods use trans-axillary, thoracoscopic or trans-hiatal laparoscopic approach, often with endoscopic assistance. Endoscopic and transoral surgical procedures include various diverticulotomy techniques and submucosal tunneling techniques (variants of peroral endoscopic myotomy). The primary concern in therapy is the reduction of symptoms, improvement of the quality of life (QOL) and the patient´s safety. The resulting QOL is affected by the frequent presence of functional diseases of the esophagus (achalasia, hypercontractile esophagus). Although surgical minimally invasive therapy using the laparoscopic or thoracoscopic approach is safe, it nevertheless does not exclude serious risk of complications. The authors concluded that randomized and observational studies comparing endoscopic and surgical methods are still missing; thus, it is necessary to extend the records in order to update the indication algorithm of intervention therapy, focusing mainly on safety with a clear imperative for patient centralization.
Klingler et al. (2021) stated that in peroral endoscopic myotomy for ZD (Z-POEM), the cricopharyngeus muscle is divided within a submucosal tunnel started in the hypopharynx. These researchers examined the safety and preliminary outcomes in patients who underwent a modified version of the Z-POEM where the tunnel is made directly overlying the cricopharyngeus, the mucosal incision and muscular interruption (MIMI) approach, and compared these with patients who underwent a non-tunneled flexible endoscopic approach. All patients with ZD who were treated by flexible endoscopy at the authors’ institution between January 2015 and February 2020 were identified by a retrospective chart review. Dysphagia symptoms were assessed using a validated scoring system. A total of 19 patients with ZD underwent MIMI (mean age of 76.1 years, 68.1% men) and 7 patients underwent non-tunneled flexible endoscopic approach (mean age of 64.4 years, 85.7% men) during the study period. Mean ZD size was 2.8 cm in the MIMI group and 1.9 cm in the non-tunneled group (p = 0.03). Clinical success was achieved in 17/19 (89.5%) MIMI patients and 7/7 (100%) of non-tunneled flexible endoscopic patients (p = 0.101). Dysphagia scores improved in both groups, although this difference was only significant in the MIMI group (p ≤ 0.001). Recurrence occurred in 2/17 (11.7%) MIMI patients and 3/7 (42.9%) non-tunneled flexible endoscopic patients (p = 0.096). There were 4 complications, including 1 pharyngeal perforation requiring open surgical repair in a patient with a small ZD with an associated cricopharyngeal bar in the MIMI group. Median length of follow-up was 290 [142 to 465] days in the MIMI group and 1,056 [258 to 1,206] days in the non-tunneled group (p = 0.094). The authors concluded that MIMI was a technically feasible and effective treatment for ZD; however, care should be taken in patients with a cricopharyngeal bar and small ZD, as this may increase the risk of perforation. Moreover, these researchers stated that larger studies with long-term follow-up are needed to determine if MIMI reduces the risk of symptom recurrence when compared to non-tunneled flexible endoscopic approaches.
Mandavdhare et al. (2021) stated that the conventional way to treat Zenker's diverticulum (ZD) has been flexible endoscopic septum division (FESD). Recently, the concept of POEM has been found useful for managing diverticular diseases of the esophagus and has been termed DPOEM. In a systematic review and meta-analysis, these investigators examined the safety and effectiveness of D-POEM in diverticular disease of the esophagus and compared it with FESD. They searched PubMed and Embase, for studies reporting clinical success, technical success and AEs in D-POEM alone or D-POEM comparing with FESD. These researchers computed pooled prevalence for D-POEM alone and risk ratio (RR) for D-POEM versus FESD using random effect method with inverse variance approach. Subgroup analysis for ZD, non-ZD and mixed diverticulum was carried out. A total of 19 studies including 341 patients were identified reporting on D-POEM. The pooled clinical, technical success and AE rates for D-POEM were 87.07%, 95.19% and 10.22%, respectively. The clinical success was significantly better than FESD while the technical success, AE rate, procedure time and LOS were comparable with FESD. The recurrence rate was negligible for D-POEM compared to FESD. On subgroup analysis by dividing into 3 groups of ZD, non-ZD and mixed, there was no difference between clinical, technical success and AE rate among the 3 groups. The authors concluded that D-POEM was a safe and effective approach among both ZD and non-ZD patients and exhibited better clinical success than FESD.
Elkholy et al. (2021) noted that POEM for the treatment of ZD (Z-POEM) is a novel technique that has been described in several recent reports. This method employs the 3rd space (submucosal layer) to create a tunnel to facilitate complete visualization of the septum and hence cutting it entirely. Conventional endoscopic septotomy carries the risk of recurrence due to incomplete visualization of the septum. In a multi-center study, these investigators examined the safety and effectiveness of Z-POEM. This trial enrolled 24 patients diagnosed with ZD who underwent Z-POEM at 7 independent endoscopy centers in 5 different countries. Mean patient age ± standard deviation (SD) was 74.3 ± 11 years. Most of the patients were men (n = 20, 83.3%); 4 (16.7%) were women. More than 50% of the patients (n = 14, 58.3%) had associated co-morbidities. The mean size of the diverticula was 4 cm (range of 2 to 7 cm). The Kothari-Haber Score was used to evaluate clinical symptoms; values ranged from 6 to 14 (median = 9). These researchers achieved 100% technical success with a median procedure time of 61 mins and no AEs. Median LOS was 1 day (range of 1 to 5 days). There was a significant reduction in the Kothari-Haber Score after Z-POEM (p < 0.0001). Technical success was achieved in 100% of the patients. Clinical success was achieved in 23/24 (95.8%) of the patients with a median follow-up of 10 months (range of 6 to 24 months). The authors concluded that Z-POEM was a safe and effective modality for managing ZD.
Samanta et al. (2022) stated that with the advent of the technique of sub-mucosal tunneling, POEM has been used for the treatment of esophageal diverticulum, which otherwise is a recurring problem with conventional flexible endoscopic treatment due to incompleteness of septotomy. In a retrospective study, these investigators reported their experience of the use of the D-POEM technique in the management of large esophageal diverticulum. This trial used a prospectively maintained database including all consecutive patients with symptomatic esophageal diverticulum presenting at a tertiary care academic center. D-POEM was carried out using the technique of submucosal tunneling and septotomy. Besides baseline parameters, technical success, clinical success, size of diverticula, procedure time, complications and symptom recurrence on follow-up were noted. A total of 5 patients (4 men; median age of 72 years) were included with an average Charlson comorbidity index of 3.2 ± 0.8. Of them, 3 had ZD while 2 had epiphrenic diverticulum. The median symptom duration was 12 months with a mean diverticulum size of 68.8 ± 1.9 mm. The mean procedure time was 64.80 ± 12.6 mins. with a mean septotomy/myotomy length of 79.44 ± 12.2 mm. Minor AEs were noted intra-procedure in 2 cases. Clinical success achieved in all cases with a significant mean dysphagia score reduction from 2.20 to 0.20 post-procedure (p = 0.011). On a median follow-up of 280 days (range of 98 to 330), none had recurrence of symptoms. The authors concluded that these findings highlighted that complete septotomy by D-POEM technique could be achieved for the management of large esophageal diverticulum and was safe and effective.
Zhang et al. (2022) noted that Z-POEM has revolutionized the therapeutic strategy for ZD with promising results. In a meta-analysis, these researchers examined the safety and effectiveness of Z-POEM for ZD and compared the feasibility and effectiveness of Z-POEM with that of flexible endoscopic septotomy (FES). They carried out a comprehensive literature search in PubMed, Embase, Web of Science, and Cochrane Library databases to query for studies that examined the safety and effectiveness of Z-POEM for ZD. All studies published from inception to July 31, 2021 were included. The primary outcomes were the overall technical success rate, clinical success rate, incidence of AEs, and clinical recurrence rate. A total of 11 studies involving 357 patients undergone Z-POEM were included. Overall, the quality of included studies was above average, with 5 studies rated as high quality and 6 ranked as moderate quality. The overall pooled technical success rate for Z-POEM was 96.3% (95% CI: 93.6% to 97.9%; I2 = 0%). The total pooled clinical success rate for Z-POEM was 93.0% (95% CI: 89.4% to 95.4%; I2 = 0%). The pooled incidence of AEs for Z-POEM was 12.4% (95% CI: 9.1% to 16.7%; I2 = 0%). The pooled clinical recurrence rate for Z-POEM was 11.2% (95% CI: 7.6% to 16.2%; I2 = 0%). The clinical success for Z-POEM was significantly better than that of FES (RR: 1.11; 95% CI: 1.03 to 1.18; p = 0.004, I2 = 0%), while there were no significant differences in technical success, AEs, and clinical recurrence between Z-POEM and FES. The authors concluded that Z-POEM could be a safe and effective therapeutic modality for ZD, and even had a slightly higher clinical success rate than FES.
Al Ghamdi et al. (2022) stated that treatment of ZD has evolved from open surgery to endoscopic techniques, including flexible and rigid endoscopic septotomy, and more recently, Z-POEM. In a retrospective, multi-center study, these investigators compared the effectiveness of flexible and rigid endoscopic septotomy with that of Z-POEM. Consecutive patients who underwent endoscopic septotomy (flexible/rigid) or Z-POEM for ZD between January 2016 and September 2019 were included. Primary outcomes were clinical success (decrease in Dakkak and Bennett dysphagia score to 1 or less), clinical failure, and clinical recurrence. Secondary outcomes included technical success and rate/severity of AEs. A total of 245 patients (110 women, mean age of 72.63 years, SD = 12.37 years) from 12 centers were included. Z-POEM was the most common management modality (n = 119), followed by flexible (n = 86) and rigid (n = 40) endoscopic septotomy. Clinical success was 92.7% for Z-POEM, 89.2% for rigid septotomy, and 86.7% for flexible septotomy (p = 0.26). Symptoms recurred in 24 patients (15 Z-POEM during a mean follow-up of 282.04 [SD 300.48] days, 6 flexible, 3 rigid [p = 0.47]). AEs occurred in 30.0% rigid septotomy patients, 16.8% Z-POEM patients, and 2.3% flexible septotomy patients (p < 0.05). The authors concluded that there was no difference in outcomes between the 3 therapeutic approaches for symptomatic ZD. Rigid endoscopic septotomy was associated with the highest rate of complications, while flexible endoscopic septotomy appeared to be the safest. Recurrence following Z-POEM was similar to flexible and rigid endoscopic septotomy.
Kahaleh et al. (2022) noted that endoscopic management of ZD has traditionally been via septotomy technique. The recent development of tunneling technique has shown to be both safe and effective. These researchers examined the tunneling technique using Z-POEM versus septotomy. Patients who underwent endoscopic management of ZD either by Z-POEM or septotomy from March 2017 until November 2020 from 9 international academic centers were included. Demographics, clinical data pre-procedure and post-procedure, procedure time, AEs, and LOS were analyzed. A total of 101 patients (mean age of 74.9 years, 55.4% men) were included: septotomy (n = 49), Z-POEM (n = 52). Pre-procedure Functional Oral Intake Scale score and Eckardt score were 5.3 and 5.4 for the septotomy group, and 5.9 and 5.15 for the Z-POEM group. Technical success was achieved in 98% of the Z-POEM group and 100% of the septotomy group. Clinical success was achieved in 84% and 92% in the septotomy versus Z-POEM groups. AEs occurred in 30.6% (n = 15) in septotomy group versus 9.6% (n = 5) in the Z-POEM group (p = 0.017). Re-intervention for ongoing symptoms occurred in 7 patients in the septotomy group and 3 patients in the Z-POEM group. Mean LOS was shorter for the Z-POEM group, at 1.5 versus 1.9 days. The authors concluded that a tunneling technique via the Z-POEM procedure was a safe and effective endoscopic treatment for ZD; Z-POEM was a safer procedure with a statistically significant reduction in AEs compared with traditional septotomy technique.
Swei et al. (2023) stated that flexible endoscopic therapy of ZD using submucosal tunneling (Z-POEM) similar to esophageal POEM is becoming increasingly common; however, data comparing Z-POEM with traditional FES were sparse. In a prospective, single-center study, these researchers compared outcomes of Z-POEM with traditional FES over a medium-term follow-up period. This trial included patients who underwent Z-POEM for treatment of ZD between 2018 and 2020 at a tertiary academic medical center compared to prior patients who had FES (between 2015 and 2018). Procedural characteristics and clinical outcomes (technical and clinical success, and AEs) were compared between patients who underwent each treatment. A total of 28 patients underwent ZD therapy during the study period -- 13 patients (mean age of 70 years; 77% men) underwent Z-POEM; and 15 patients (mean age of 72 years; 73% men) underwent traditional FES. The mean ZD size was 2.4 ± 0.6 cm in the ZPOEM group versus 2.5 ± 0.8 cm in the FES group. The mean procedure time was similar between groups: 43.9 mins (range of 26 to 66 mins) in the Z-POEM group and 60.2 mins (range of 25 to 92 mins) in the traditional FES group (t = 1.74, p = 0.19). Overall technical success was observed in 100% of patients. There was 1 AE in the FES group (dehydration resulting in near-syncope) (1/28, 3.6%). Overall clinical success was observed in 92.8% (26/28) of patients and was not significantly different between groups (Z-POEM; 13/13, 100% versus FES; 13/15, 86.7%, t = - 1.36, p = 0.18). The authors concluded that the findings of this prospective study suggested that Z-POEM was an effective technique for the treatment of ZD with no significant differences in clinical outcomes or AE rates when compared to traditional FES. Moreover, these researchers stated that larger prospective, longer-term, controlled studies are needed to fully compare the 2 techniques.
The authors stated that this study had several drawbacks. First, this trial was carried out at a single center with a limited number of patients, and recruitment was impacted by the COVID-19 pandemic. Patients who underwent Z-POEM were recruited consecutively (2018 to 2020) and compared to previous ZD patients who had FES (2015 to 2018), which may have introduced selection bias into the cohort owing to improvements in technology over the study periods, including availability of endoscopic equipment, accessories and refinements in technique developed over time that were not accounted for in the analysis. Second, these investigators realized that since this study compared the 2 techniques over different time periods, with a finite number of patients in the FES control group, these researchers were unable to conduct sample size calculations. As a result, these investigators may only be able to detect large differences between Z-POEM and FES groups and smaller differences may have been missed. Third, all procedures (Z-POEM and FES) were carried out by a single endoscopist, and data analysis did not account for changes or improvement in procedural technique over time. Fourth, follow-up data were collected via phone call if not available from clinical encounters, which may have introduced reporting bias. These findings differed from a recently published systemic review and meta-analysis that showed that Z-POEM had higher clinical success than FES (Desai et al., 2020). However, improvements in Z-POEM technique, and smaller numbers of patients with high clinical success may account for this differing result. Fifth, this trial did not compare the use of the 2 techniques for various ZD sizes and they also were unable to comment on the cost-effectiveness of the 2 techniques.
These investigators noted that several other considerations should be noted when clinically comparing and choosing between the 2 treatment modalities. First is that Z-POEM requires advanced technical skills, an endoscopist trained in endoscopic submucosal dissection; and may require the use of the more specialized knives, which may not be feasible at all centers, although notably these researchers have previously reported that the choice of knife used did not have significant impact on procedural outcomes. Second, the Z-POEM procedure requires the use of multiple endoscopic clips, which may add to the cost of the procedure. Third, although general anesthesia was used for both procedures in the authors’ center as per anesthesia recommendations, FES can be performed safely with moderate or deep sedation (monitored anesthesia care), which depending on anesthesia availability may factor into the choice of procedure.
Buyruk and Erdogan (2024) stated that the safety and effectiveness of Z-POEM have been reported in a limited number of studies and case-reports. In a single-center study, these investigators reported their experience with the Z-POEM method. Patients with ZD who were treated with Z-POEM between January 2019 and March 2023 and had a follow-up period of at least 3 months were included in the study. The primary endpoint was clinical success. A Kothari-Haber score (KHS) of 2 or less at 1 month post-operatively was defined as clinical success; and the secondary endpoints were AEs and recurrence rates. A total of 20 patients (65% men; mean age of 63 ± 14.4 years) were treated with Z-POEM. The mean ZD septum length was 33.7 (± 11.04) mm. The technical success rate was 100% (20/20), and the clinical success rate was 95% (19/20). In 1 case with a large ZD (septum length of 60 mm), the mucosal septum, which was thought to cause partial persistence of symptoms, was treated by endoscopic septotomy. The mean KHS decreased significantly after Z-POEM (pre-operative KHS: 7.3, and post-operative KHS: 0.15, p <0 .0001). The median follow-up period was 10 months (IQR, 3 to 39). No recurrence was observed. Intra-procedural mild subcutaneous emphysema was observed in 4 (20%) cases. Emphysema regressed spontaneously in the post-operative period without any treatment. The authors concluded that the results obtained in this trial showed that Z-POEM was safe and effective for the treatment of ZD; and Z-POEM is also a promising method in terms of short-term recurrence.
The authors stated that this trial and most studies in the literature included cases reported by tertiary centers; thus, limiting the generalizability of the results for less experienced centers. Furthermore, the small number of patients in the present study was another drawback. Considering that ZD is a rare condition, the authors believed that this case-series study will increase the sample size for future studies and contribute to the evidence of the safety and effectiveness of Z-POEM. These researchers noted that another drawback was the short follow-up period of the patients. In this patient group, only 7 cases had a follow-up period of over 1 year. This significantly hindered the authors’ ability to comment on the long-term recurrence rates after Z-POEM. However, given that Z-POEM has been available in Turkey for the past 4 years, future studies will address this issue as follow-up periods extend.
Temporary Gastric Electrical Stimulation (GES) for the Prediction of Success of GES in the Treatment of Gastroparesis
Elfvin et al. (2007) noted that temporary electrodes implanted under general anesthesia, or via an oral or percutaneous endoscopic gastrostomy route have been used for testing of GES. These investigators have developed a principle for percutaneous electrode implantation. Leads were constructed so that the tip could be anchored to the gastric submucosa under gastroscopic control. Acute experiments were performed in anaesthetized pigs. In addition, a total of 3 patients referred for nausea and/or vomiting and non-established indications for GES (chronic intestinal pseudo-obstruction, functional dyspepsia without gastroparesis) were evaluated. Electrode function was tested by recording and stimulation techniques. In the pigs, a slow-wave (SW) rhythm (3 min(-1)) was recorded with decrease in frequency at the end of the experiments. In the patients, implantation time from start of gastroscopy to end of electrode placement was 12 to 20 mins. Electrode distance varied from 12 to 45 mm. Gastric electromyography (EMG) showed a regular SW rhythm of about 3 min(-1). Antral pressure waves had intervals being multiples of the SW-to-SW time. With temporary GES for 7 to 9 days, weekly frequency of the referral symptoms decreased greater than 80% in 2 patients and 33% in 1 patient. The authors concluded that temporary percutaneous gastric leads could easily be implanted and may be used for testing of GES and study of gastric electrophysiology.
Andersson et al. (2011) tested temporary percutaneous GES (TPGES) in patients with drug-refractory nausea/vomiting and non-established indications for GES. A total of 27 patients (2 to 81 years) underwent TPGES with electrodes implanted at gastroscopy and received stimulation for 7 to 21 days with low current settings (5 to 7 mA) either as open stimulation (n = 14) or randomized to double-blind cross-over stimulation (n = 13; ON for 12 to 14 days, OFF for 12 to 14 days). Symptoms were recorded daily. Non-responders were offered another period (14 to 21 days) with increased stimulation (8 to 10 mA). Mean lead implantation time was 14 mins. Leads were kept implanted for 60 days or less; 22 of 27 evaluable patients had a favorable symptom reduction, preferentially of nausea/vomiting, irrespective of delayed or normal gastric emptying rate: post-surgical gastroparesis 7/8, chronic intestinal pseudo-obstruction 2/2, idiopathic gastroparesis 1/1, functional dyspepsia 6/9, diabetes mellitus 2/2, post-surgical nausea/vomiting 2/2, malformation syndrome 1/1, intestinal neuropathy 1/1, intestinal interstitial cells of Cajal deficiency 0/1. A total of 6 patients had a clear symptom reduction during the ON period compared with stimulation OFF; 4 of 7 patients improved with increased stimulation (8 to 10 mA); 20 of the 22 responders received a permanent GES implant, 90% of them still being responders at last follow-up. The authors concluded that TPGES appeared promising to study new indications for GES and to select responders/non-responders.
Abell et al. (2011) stated that endoscopically placed, temporary GES (tGES) may relieve symptoms of gastroparesis (Gp) and predict permanent GES outcomes. In a double-masked, randomized, placebo-controlled trial of temporary endoscopic mucosal GES for gastroparesis, these researchers examined the effects of 72 hours of temporary GES on Gp symptoms. From 2005 to 2006, these investigators carried out a hospital-based, cross-over trial of 2 consecutive, 4-day sessions (session 1 and session 2), enrolling 58 patients (11 males, 47 females; mean age of 46 years) with GP symptom histories of 3 etiologies (idiopathic = 38; diabetes mellitus = 13; and post-surgical = 7). A total of 72 continuous hours tGES was provided for group A during session 1, and for group B during session 2. Main outcome measurements included symptoms measured daily; gastric emptying, electrogastrography (EGG), and QOL measured at baseline and session close. In session 1, vomiting decreased in both groups, but was greater with stimulation, resulting in a day 3 difference of -1.02 (95% CI: -1.62 to -0.42; p < 0.001). Scores did not return to baseline during wash-out; on day 4, the difference persisted at -1.08 (95% CI: -1.81 to -0.35; p = 0.005). In session 2, vomiting slightly decreased with stimulation and slightly increased without it; at day 8, the non-activated group had non-significantly greater vomiting, 0.12 (-0.68 to 0.92; p = 0.762). An overall treatment effect of a slight, non-significant daily decrease in average vomiting scores, -0.12 (-0.26 to 0.03; p = 0.116), was observed by pooling stimulation effects across sessions. The authors concluded that although overall treatment effects were non-significant, differences in favor of stimulation were suggested. Barriers to observing treatment effects included a decrease in vomiting for both groups during session 1, insufficient wash-out, and the absence of baseline vomiting for some patients. Moreover, these researchers stated that future studies should better define inclusion criteria, use longer wash-out periods, randomize by etiology and baseline physiological findings, and pursue alternative designs.
The authors stated that this study had several drawbacks. First, the number of patients examined was small (n = 58) and electrode dislodgment occurred in 13 patients (22%). Some results that were not statistically significant might become so with a larger sample size. The tGES protocol now uses trans-nasal rather than orally placed leads, which have greatly reduced dislodgment rates. Second, the 24-hour wash-out period may have been insufficient to eliminate the effects of stimulation. Potential carry-over effects should be addressed by the use of alternative study designs (e.g., parallel groups, longer study/wash-out periods, stepped-wedge designs). Third, these researchers observed symptom and physiologic differences between groups A and B at baseline in spite of randomization, which could have happened by chance alone in any given study. The imbalances they observed may impede a clear examination of the underlying questions of interest. Post-hoc analyses that controlled additionally for baseline variables (baseline vomiting, nausea, mucosal EGG frequency and amplitude) provided similar results, with reported primary pooled treatment effect on vomiting = −0.12 (−0.26, 0.03), p = 0.116, and pooled treatment effect with additional baseline variable adjustment = −0.10 (−.23, 0.06), p = 0.253. To avoid similar difficulties in future studies, these investigators recommended that baseline symptom status and electrophysiology be taken into account when constructing the randomization protocol, and especially baseline mucosal EGG recorded following mucosal lead placement, but before stimulator activation. Furthermore, mucosal EGG should be examined for its potential use as an indicator of permanent stimulator outcomes. Fourth, these researchers elected in this study to leave all the patients on the at-home medications for nausea or pain that they were using at the time of baseline assessment. In group A (n = 28), 17 patients (60.71%) were on prokinetics, and 16 (57.14%) were on anti-emetics. In group B (n = 30), 23 patients (76.67%) were on prokinetics, and 18 (60%) were on anti-emetics. Finally, there were missing data, and potential physiological imbalances between groups.
Corvinus et al. (2018) noted that Gp is defined as delayed gastric emptying (GE) without any obstruction of the pylorus. It can be divided into idiopathic, diabetic, post-surgical and rare causes. Electronic gastric stimulation (EGS) is a part of Gp therapy. Although its positive impact has been reported in open-label trials, RCTs failed in showing a positive outcome. In a pilot study, these researchers attempted to establish a reliable prediction for permanent gastric stimulation. A total of 6 female patients underwent laparoscopic implantation of 2 temporary electrodes. The Enterra System (Medtronic) was connected and taped to the skin. Baseline and post-operative GCSI was assessed. Response to EGS was defined as a 50% decrease of baseline GCSI. A total of 4 of 6 patients responded to temporary EGS; 3 of 4 responders underwent permanent implantation; 1 non-responder received a permanent Enterra System at another institution. After a median follow-up time of 9 months the responder group GCSI remained low, whereas the non-responder GCSI had increased. Moreover, the healthcare system was saved € 30,678.03 by this test stimulation concept. The authors concluded that laparoscopic implantation of a temporary EGS system predicted the outcome of permanent gastric stimulation and was cost-saving.
Shine et al. (2022) stated that GES is a widely accepted therapy for Gp symptoms; however, how a brief cutaneous EGG can be used in conjunction with GES has not been well-defined. These researchers examined the clinical importance of EGG, its correlation with mucosal electrograms (mEGs), gastric emptying tests (GETs), and GI symptoms before and after tGES. These investigators studied 1,345 patients; 991 had complete data. EGG measurements like frequency and amplitude were recorded at baseline and 5 days post-tGES using short recording periods. A total of 266 subjects having additional cutaneous propagation values were separately analyzed. Patients underwent solid GET before and after tGES and self-reported symptoms using standardized traditional patient-reported outcomes (TradPRO) scores. Pearson correlations were assessed at baseline, post-stimulation, and their changes over the follow-up period. EGG measures correlated with symptoms and GET results. Patients with abnormal baseline cutaneous frequency had higher baseline total symptom scores (p < 0.003). Post-tGES, 1-hour gastric emptying was significantly changed (p < 0.0001) and was mainly observed with abnormal baseline cutaneous frequencies (p < 0.0001). Cutaneous frequency significantly increased after tGES (p < 0.0001), correlating positively with TradPRO scores and 1-hour gastric emptying. Mucosal and cutaneous measures correlated pre- and post-treatment. Of the 266 patients, 153 changed propagation states between baseline and temporary; changing states from lower at baseline to higher at temporary was more likely than vice-versa. Short EGG recording times could demonstrate changes after the bioelectric therapy of GES. The authors concluded that EGG was valuable in the diagnosis of delayed gastric emptying and comparable with mEG. It was less invasive and could identify patients who may require GES. Frequency, amplitude, their ratio (frequency-amplitude ratio), and propagation appeared to be reliable measures of EGG. These researchers stated that EGG provided cost-effective measurement of electrophysiological properties and significantly correlated with important clinical measures; shorter EGG recording times may be adequate to see changes from bioelectric therapies.
Soliman and Gourcerol (2022) stated that GES is currently used as an alternative treatment for medically refractory Gp. GES has been initially developed to accelerate gastric motility, in order to relieve the symptoms of the patients. Subsequent studies, unfortunately, failed to demonstrate the acceleration of gastric emptying using high-frequency stimulation - low energy stimulation although the technique has shown a clinical impact with a reduction of nausea and vomiting for patients with Gp. Moreover, these researchers stated that an approach to select better responders to GES could be the use of temporary GES. This technique entails either the electrode placement via a G-tube or using the endoscopic placement of cardiac pacing leads into gastric mucosa. The latter technique involves an inner bipolar electrode pacing lead and is left like a naso-gastric (NG) tube. Electrodes are then connected to an external standard device, in a shirt pocket and adjusted with the same parameters as the Enterra therapy. In a randomized trial, temporary stimulation led to a reduction in the vomiting frequency, even if not significant due to some limitations of the study design (Abell et al., 2011. This technique has also been evaluated over 551 patients suffering from symptoms of Gp and was effective in patients with or without delayed gastric emptying. These investigators noted that tGES revealed improvement in vomiting, nausea, and total symptom severity score. Finally, the study by Corvinus et al. (2018) revealed that patients who had a clinical improvement with tGES were responders to GES therapy. Moreover, the location of the implantation of electrodes can be easily changed with temporary stimulation. Therefore, this technique could help define the best location for the electrodes according to gastric innervation. These researchers stated that the main drawback of tGES was that the technique is not currently commercially available.
Balloon Dilation Test for Identification of Candidates for Gastric Peroral Endoscopic Myotomy
Gantuya et al. (2025) noted that predicting successful outcomes of G-POEM is crucial for identifying patients who are most likely to benefit from the procedure. In a retrospective, pilot study, these researchers examined the use of the balloon dilation test (BDT) in optimizing patient selection for G-POEM. This trial was carried out from February 2021 to December 2023; it included patients with refractory GP unresponsive to conventional medical treatments. All participants completed the GCSI questionnaire before and after G-POEM. The pyloric ring BDT was conducted before G-POEM, with only patients who showed a positive response included. Procedural and clinical outcomes were analyzed. A total of 5 patients (3 women and 2 men) with refractory GP were included. The median age of the cohort was 60 years (IQR 47.5 to 75). The median G-POEM procedure time was 60 mins (IQR 32.5 to 110), and technical success was achieved in all cases. At a median follow-up of 10 months (IQR 6 to 34), clinical response was observed in all patients (100%). The GCSI score improved significantly from a median of 17 (IQR 8 to 33) to 0 (IQR 0 to 4.5; p < 0.03) indicating significant improvement in clinical symptoms. The authors concluded that a positive response to the BDT appeared to be a reliable predictor of successful short-term outcomes following G-POEM in patients with refractory GP. Moreover, these researchers stated that larger, prospective studies incorporating advanced diagnostic methods (e.g., gastric emptying scintigraphy) are needed to validate these findings and optimize patient selection criteria for this procedure.
The authors stated that this trial had several drawbacks. First, the small sample size (n = 5) was a significant limitation, reducing the statistical power and generalizability of the findings. Second, the absence of long‐term follow‐up further limited the assessment of the sustainability of the outcomes. Third, incorporating standardized diagnostic methods, such as gastric emptying scintigraphy, in future studies would provide a more objective assessment of gastric motility and improve the reliability of the results. A comparative study with a non‐BDT group could also provide valuable insights, helping to further validate the hypothesis and better understand the relative benefits of the treatment. Fourth, while the non‐invasive GCSI score provided useful preliminary insights in this pilot study, future studies should adopt more comprehensive evaluation methods to strengthen the conclusions.
Endoscopic Functional Luminal Imaging Probe (EndoFLIP) for Prediction and Evaluation of Outcomes with Gastric Peroral Endoscopic Myotomy (G-POEM)
Varghese et al. (2024) noted that GP is a debilitating gastro-duodenal disorder for which G-POEM has emerged as an effective therapeutic option; however, response to G-POEM varies between 50% and 80%, such that pre-operative predictors of treatment success are needed to guide patient selection. In a systematic review, these investigators identified predictors of clinical and functional response to G-POEM among adult patients with GP. They searched Medline, Embase, and CENTRAL data-bases for studies reporting outcomes following G-POEM in September 2023. They carried out a narrative synthesis of predictive factors on uni-variable and multi-variable analysis with consideration of response rates via meta-analysis and evaluation of discrimination if prognostic models were developed. Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) was employed for risk of bias assessment. These investigators reviewed a total of 1,899 studies, and 30 were included. The G-POEM response rate was 63.1% (95% CI: 56.3% to 69.5%) with most studies defining clinical success on the basis of improvement in GP cardinal symptom index (87%, 26/30). Older age, shorter duration of GP, non-diabetic etiology, lower BMI, and response to intra-pyloric BTX were associated with positive response to G-POEM on multi-variable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation. The authors concluded that currently, there are limited reproducible predictors of response to G-POEM among patients with refractory GP; rigorous, prospective studies examining scalable, reproducible, and actionable biomarkers of treatment response are needed.
Farooq et al. (2025) stated that functional luminal imaging probe (FLIP) evaluates pyloric sphincter physiology. In a prospective, single-center study, these researchers employed FLIP to assess the association between pyloric measurements and clinical outcomes of G-POEM in patients with refractory gastroparesis. This trial included patients who underwent G-POEM between January 2022 and March 2024. FLIP was carried out pre-G-POEM, immediately post-G-POEM and at follow-up (median of 6 months). Clinical response was defined as an improvement of 1 point or more on the GCSI; and ROC was constructed to examine the relationship between FLIP measurements and response to G-POEM. Clinical response was achieved in 64 out of 90 (71.1%) at a median of 6-months. Pre-G-POEM FLIP mean DI was significantly lower among responders versus non-responders (7.1 ± 2.8 versus 9.2 ± 3.1 mm2/mm Hg; p =0.002). Mean DI increased significantly in both groups immediately after G-POEM, but this remained persistently elevated only among responders (10.4 ± 4.4 mm2/mm Hg; p = 0.02), while returning towards baseline among non-responders (9.7 ± 4.7 mm2/mm Hg; p = 0.69) at 6-month follow-up. Pre-G-POEM DI with an AUC of 0.72 yielded a specificity of 80.8% and sensitivity of 60.6% at a cut-off point of 7.35 mm2/mm Hg. The authors concluded that sustained improvement in pyloric FLIP measurements was observed in patients who endorsed a clinical response to G-POEM. Patients who responded to G-POEM had a lower baseline DI when compared to non-responders. Moreover, these researchers stated that further investigations optimizing and standardizing FLIP protocols in patients undergoing G-POEM are needed.
Endoscopic Functional Luminal Imaging Probe (EndoFLIP) for Prediction of Clinical Success Before Gastric Peroral Pyloromyotomy (G-POP)
Williams et al. (2025) noted that gastric peroral pyloromyotomy (G-POP) is a minimally invasive endoscopic technique for the treatment of refractory GP. The FLIP is an endoscopic tool for measuring the physiologic parameters of the GI sphincters. In a prospective, single-center study, FLIP was employed to examine the association between physiologic measurements of the pylorus and clinical outcomes following G-POP using the GCSI to monitor clinical response. This trial included 48 patients with GP who underwent G-POP for the management of refractory GP. The cross-sectional area (CSA), pressure, as well as DI of the pylorus were assessed using FLIP at 40-ml and 50-ml balloon fill volumes pre- and post-procedurally. GCSI scores were used to monitor clinical symptoms both pre-procedurally and at 6 weeks after G-POP. Technical success was achieved in 100% of patients. GCSI scores (0 to 5) decreased by an average of 0.95 ± 1.45 points at 6 weeks post-operatively, with the nausea/vomiting and bloating subscales showing the greatest improvement. The change (∆) in DI at 50-ml balloon fill volumes was a statistically significant predictor of symptomatic improvement after the procedure, with ∆DI at 50 ml of greater than 1.5 mm2/mm Hg strongly correlated with larger improvements in GCSI (Pearson coefficient: 0.544; p = 0.036). The authors concluded that the EndoFLIP was not found to be a reliable predictor of clinical success before G-POP; however, measuring changes pre- and post-procedurally could be used to guide management. These researchers stated that further investigations are needed to elucidate the relationship between physiologic pyloric sphincter measurements and clinical response to G-POP.
Per-Oral Endoscopic Myotomy (POEM) for Treatment of Achalasia
Pescarus et al. (2014) stated that POEM is a new minimally invasive endoscopic treatment for achalasia. Since the first modern human cases were published in 2008, around 2,000 cases have been performed worldwide. This technique requires advanced endoscopic skills and a learning curve of at least 20 cases. Per-oral endoscopic myotomy is highly successful, with over 90% improvement in dysphagia while offering patients the advantage of low-impact endoscopic access. The main long-term complication is GER, with an estimated incidence of 35%, similar to the incidence of GER post-laparoscopic Heller with fundoplication. The authors concluded that although POEM represents a paradigm shift in the treatment of achalasia, more long-term data are needed to further define its role in the treatment algorithm of this rare disease.
Bredenoord et al. (2014) noted that treatment of achalasia is complicated by symptom recurrence and a significant risk for severe complications. Endoscopic myotomy was developed in the search for a highly effective treatment with lower risks. Since its introduction in 2010, several centers have adopted the technique and published excellent short-term results of open-label series. These researchers stated that randomized trials with long-term endpoints comparing POEM with the established treatments such as balloon dilation and surgical myotomy are now warranted before POEM can be regarded as the routine clinical care for achalasia patients.
Schlottmann et al. (2018) compared the outcomes of per-oral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for the treatment of esophageal achalasia. These researchers performed a systematic Medline literature search of articles on LHM and POEM for the treatment of achalasia. The main outcomes measured were improvement of dysphagia and post-treatment gastro-esophageal reflux disease (GERD). Linear regression was used to model the effect of each procedure on the different outcomes. A total of 53 studies reported data on LHM (5,834 patients), and 21 articles examined POEM (1,958 patients). Mean follow-up was significantly longer for studies of LHM (41.5 versus 16.2 months, p < 0.0001). Predicted probabilities for improvement in dysphagia at 12 months were 93.5% for POEM and 91.0% for LHM (p = 0.01), and at 24 months were 92.7% for POEM and 90.0% for LHM (p = 0.01). Patients undergoing POEM were more likely to develop GERD symptoms (odds ratio [OR] 1.69, 95% confidence interval [CI]: 1.33 to 2.14, p < 0.0001), GERD evidenced by erosive esophagitis (OR 9.31, 95% CI: 4.71 to 18.85, p < 0.0001), and GERD evidenced by pH monitoring (OR 4.30, 95% CI: 2.96 to 6.27, p < 0.0001). On average, the length of hospital stay was 1.03 days longer after POEM (p = 0.04). The authors concluded that short-term results showed that POEM is more effective than LHM in relieving dysphagia, but it is associated with a very high incidence of pathologic reflux. The clinical sequelae of the increase in pathologic reflux are currently unclear, but it is possible that longer-term outcomes associated with POEM may demonstrate GERD complications such as stricture and/or Barrett esophagus. These researchers stated that longer follow-up studies and randomized trials comparing POEM to LHM are needed to establish the role of this new technique in the treatment algorithm of achalasia.
The authors stated that this study had several drawbacks. Due to the rarity of achalasia, few controlled trials were available for analysis, and most of the studies reviewed by these investigators were retrospective or cohort studies, subject to selection bias and reporting bias. In addition, POEM studies have significantly shorter follow-up compared with LHM studies, which may influence the results. As noted above, POEM is also a newer technology, and the extent to which outcomes change as operators exit their learning curves is unclear. Heterogeneity in reporting outcomes among studies may have also affected the results and limited the categorization of outcomes into simple dichotomous variables that could be easily quantified. LHM studies, in general, evaluated their primary outcomes by the improvement in swallowing status; POEM studies, on the other hand, most commonly assessed outcomes using the Eckardt score, a more precise evaluation as it considers not only the improvement in dysphagia but also the effect of the procedure on regurgitation, retro-sternal pain, and weight loss.
In a systematic review and meta-analysis, Awaiz et al. (2017) compared the safety and effectiveness of LHM and POEM for the treatment of achalasia. These investigators carried out a search of PubMed, Cochrane database, Medline, Embase, Science Citation Index, and current contents for English-language articles comparing LHM and POEM between 2007 and 2016. Variables analyzed included prior endoscopic treatment, prior medical treatment, prior Heller myotomy, operative time, overall complications rate, post-operative GERD, length of hospital stay, post-operative pain score, and long-term GERD. A total of 7 trials consisting of 483 (LHM = 250, POEM = 233) patients were analyzed. Pre-operative variables (e.g., prior endoscopic treatment [OR, 1.32; 95% CI: 0.23 to 4.61; p = 0.96], prior medical treatment [weighted mean difference (WMD), 1.22; 95% CI: 0.52 to 2.88; p = 0.65], and prior Heller myotomy (WMD, 0.47; 95% CI: 0.13 to 1.67; p = 0.25) were comparable. Operative time was 26.28 minutes, non-significantly longer for LHM (WMD, 26.28; 95% CI: -11.20 to 63.70; p = 0.17). There was a comparable overall complication rate (OR, 1.25; 95% CI: 0.56 to 2.77; p = 0.59), post-operative GERD rate (OR, 1.27; 95% CI: 0.70 to 2.30; p = 0.44), length of hospital stay (WMD, 0.30; 95% CI: -0.24 to 0.85; p = 0.28), post-operative pain score (WMD, -0.26; 95% CI: -1.58 to 1.06; p = 0.70), and long-term GERD (WMD, 1.06; 95% CI: 0.27 to 4.1; p = 0.08) for both procedures. There was a significantly higher short-term clinical treatment failure rate for LHM (OR, 9.82; 95% CI: 2.06 to 46.80; p < 0.01). The authors concluded that POEM compared favorably to LHM for achalasia treatment in short-term peri-operative outcomes. However, there was a significantly higher clinical treatment failure rate for LHM on short-term post-operative follow-up. They stated that currently long-term post-operative follow-up data for POEM beyond 1 year are unavailable and eagerly awaited. They stated that presently, long-term post-operative follow-up data for POEM beyond 1 year are unavailable in all the comparative trials and therefore meaningful comparison with LHM is impossible. In the future, several issues need to be addressed to determine the clinical outcomes, safety, and effectiveness of these 2 methods for achalasia treatment. These include the following:
- standardized definition of failure rate;
- standardized method of detecting recurrence of achalasia (e.g., timed barium swallow, high-resolution manometry, FLIP, and 24-hour pH monitoring); and
- long-term post-procedural data collection using disease-specific–validated instruments to gauge the effectiveness and durability of POEM.
These researchers stated that until all the above-mentioned issues are rigorously addressed in a well-designed randomized controlled trial comparing POEM with LHM, the routine use of POEM should proceed with caution.
Crespin et al. (2017) performed a systematic review of the literature to evaluate the safety and effectiveness of POEM for the treatment of achalasia. The systematic review was conducted following the PRISMA guidelines. Evidence-Based Medicine Reviews, Cochrane Central Register of Controlled Trials, and Ovid MEDLINE (R) including in-process and non-indexed citations were searched for POEM studies using the keywords: esophageal achalasia, POEM, endoscopy, natural orifice surgery, laparoscopic Heller myotomy (LHM), and related terms. Eckardt score, lower esophageal sphincter (LES) pressure, and reported complications were the main outcomes. Two authors reviewed the search results independently. A third reviewer resolved all disagreements. Data abstraction was pilot-tested and approved by all authors. Data were examined for clinical, methodological, and statistical heterogeneity with the aim of determining whether evidence synthesis using meta-analysis was possible. The search strategy retrieved 2,894 citations. After removing duplicates and applying the exclusion criteria, 54 studies were selected for full-text review, of which a total of 19 studies were considered eligible for further analysis. There were 10 retrospective and 9 prospective studies, including 1,299 POEM procedures. No randomized control trial (RCT) was identified. Overall, the pre- and post-POEM Eckardt scores and LES pressure were significantly different. The most frequently reported complications were mucosal perforation, subcutaneous emphysema, pneumoperitoneum, pneumothorax, pneumomediastinum, pleural effusion, and pneumonia. The median follow-up was 13 months (range of 3 to 24). The authors concluded that POEM is a safe and effective alternative for the treatment of achalasia. However, only short-term follow-up data compared with LHM are available. These investigators stated that RCTs and long-term follow-up studies are needed to establish the safety and effectiveness of POEM in the management of patients with achalasia.
Hernandez Mondragon et al. (2017) noted that POEM is an excellent endoscopic treatment for achalasia. Clinical and manometric parameters are used for evaluation and follow-up. However, clinical success does not guarantee high quality of life (QOL) scores, generating doubts about their direct relationship. These researchers evaluated QOL scores before and after POEM at medium- and long-term intervals to evaluate differences between achalasia subtypes and find which factors are related to low QOL scores. Achalasia-confirmed patients undergoing POEM between February 2012 and November 2016 and completing at least 1 year of follow-up were included. Assessment before and at 1, 6, 12, 24, 36, and 48 months after POEM employed manometry, barium series, Eckardt score, and the AE-18 health-related QOL scale. Demographic, clinical, and procedure characteristics were documented, with comparisons between subgroups. Multiple logistic regression analysis was done; 65 of 88 patients were included (38 women and 27 men; median age of 47 years, interquartile range [IQR] 20 to 81), and 50 (76.9%) completed 4 years of follow-up. The Eckardt score improved (median, pre-procedure 10 versus post-procedure 2; p = 0.002), and this persisted. There was initial improvement in median integrated relaxation pressure (IRP) (29.4 mmHg [16 to 55] versus 10.3 mmHg [3 to 18]; p = 0.000) and median QOL scores (40 versus 68 at 1 month; p = 0.002); however, IRP increased and QOL scores decreased. Men with confirmed type III achalasia had low QOL scores. The authors concluded that all patients had significant clinical improvement after POEM, with medium- to long-term persistence. These investigators noted that although quality of life and IRP initially improved, they deteriorated in the long term; male sex and type III achalasia appeared to be associated with low QOL scores.
Liu et al. (2017) stated that with the development of endoscopic interventions and inspired by the success of POEM for the treatment of achalasia, these researchers investigated an old method of direct POEM without a submucosal tunnel for the treatment of achalasia, which these investigators called open POEM (O-POEM). In this study, clinical success was achieved in the patient after O-POEM. A reduction of LES pressure, Eckardt score, and a timed barium esophagogram were observed during follow-up. There were no severe complications and no recurrences during 2 months of follow-up. The authors concluded that O-POEM is a feasible and effective endoscopic treatment modality for achalasia. However, long-term outcomes of O-POEM require further follow-up.
Banks and Sweis (2017) stated that achalasia is a rare esophageal motility disorder predominantly causing dysphagia and regurgitation of food and fluids. Diagnosis is typically made after a combination of tests including endoscopy, barium swallow, and esophageal manometry. The advent of high-resolution manometry has led to the Chicago Classification that divides achalasia into 3 types. This improved the understanding of presentation, prognosis, and might also help tailor therapy. Botulinum toxin has been shown to have good but short-term efficacy. The predominant treatments include pneumatic balloon dilatation and laparoscopic Heller's myotomy, both of which have similar and durable outcomes, although the success of both reduces with time; POEM has been shown to be as effective, safe, and durable as earlier treatments for achalasia; however, RCTs are lacking. The authors noted that indications for POEM are expanding to other hyper-contractile motility disorders of the esophagus.
Nabi et al. (2017) stated that POEM has emerged as an efficacious treatment modality for the management of achalasia cardia (AC) and non-achalasia spastic esophageal motility disorders. Initial results are encouraging. These investigators analyzed the safety and effectiveness of POEM in a large cohort of patients with AC. The data from patients who underwent POEM (from January 2013 to June 2016) were prospectively collected and analyzed. Clinical success was defined as an Eckardt score less than or equal to 3 after the POEM procedure. Objective parameters including high-resolution manometry (HRM) and timed barium swallow (TBS) were analyzed and compared before and after the procedure. Gastro-esophageal reflux was analyzed using a 24-hour pH impedance study and esophago-gastro-duodenoscopy. A total of 408 patients (mean age of 40 years, range of 4 to 77 years) underwent POEM during the specified period. POEM could be successfully completed in 396 (97%) patients. Clinical success rates at 1, 2, and 3 years were 94%, 91%, and 90%, respectively. The mean Eckardt score was 7.07 ± 1.6 prior to POEM and 1.27 ± 1.06 after POEM (p = 0.001) at 1 year. Significant improvement in esophageal emptying on TBE (greater than 50%) was documented in 93.8% of patients who completed 1-year follow-up. Pre-procedure and post-procedure mean lower esophageal sphincter pressure was 45 ± 16.5 mmHg and 15.6 ± 6.1 mmHg, respectively (p = 0.001). Technical and clinical success were comparable in naïve versus prior treated cases (97.3% versus 96.8%, p = 0.795) (95.7% versus 92.6%, p = 0.275). GERD was documented in 28.3% of patients with a 24-hour pH-impedance study, and erosive esophagitis was seen in 18.5% of patients who underwent POEM. The authors concluded that POEM is safe, effective, and durable for the treatment of AC. The incidence of GERD did not appear to be higher than with LHM. However, randomized comparisons are needed; whether POEM should be offered as a first-line treatment to all patients with AC is a matter of debate. Moreover, they stated that long-term follow-up studies and randomized comparisons with established modalities such as PBD and LHM will provide conclusive information in that regard.
Schlottmann and Patti (2018) noted that esophageal achalasia is a rare disorder characterized by a failure of the LES to relax during swallowing, combined with aperistalsis of the esophageal body. Treatment is not curative but aims to eliminate the outflow resistance caused by the non-relaxing LES. Current evidence suggests that both laparoscopic Heller myotomy and POEM are very effective in the relief of symptoms in patients with achalasia. Specifically, for type III achalasia, POEM may achieve higher success rates. However, POEM is associated with a very high incidence of pathologic reflux, with the risk of exchanging one disease—achalasia—with another, gastro-esophageal reflux.
Kroch and Grimm (2018) stated that POEM was introduced in 2008 for the treatment of esophageal achalasia. It is performed endoscopically, which allows transection of the muscular fibers of the distal esophagus and of the LES. The procedure is therefore similar to a laparoscopic Heller myotomy without a fundoplication. Short-term studies have shown that POEM is very effective in relieving dysphagia and regurgitation, but concerns have been raised about the incidence of post-POEM gastro-esophageal reflux. The authors concluded that prospective and randomized trials are needed to determine the role of this new procedure in the treatment algorithm of esophageal achalasia.
Repici and colleagues (2018) stated that POEM represents a less invasive alternative to conventional laparoscopic Heller's myotomy (LHM) for patients with achalasia. However, it cannot be excluded that the lack of fundoplication after POEM may result in a higher incidence of reflux disease compared with LHM. These researchers conducted a systematic review of prospective studies reporting the incidence of reflux disease developed after POEM and LHM. A literature search with electronic databases was performed (up to February 2017) to identify full articles on the incidence of gastro-esophageal reflux symptoms and endoscopic monitoring and pH monitoring findings after POEM and LHM (with fundoplication). Proportions and rates were pooled by means of random or fixed-effects models, according to the level of heterogeneity between studies. After the selection criteria were applied, 17 and 28 studies, including 1,542 and 2,581 participants who underwent POEM and LHM, respectively, were included. The pooled rate of post-procedural symptoms was 19.0% (95% confidence interval [CI]: 15.7% to 22.8%) after POEM and 8.8% (95% CI: 5.3% to 14.1%) after LHM, respectively. The pooled rate estimate of abnormal acid exposure at pH monitoring was 39.0% (95% CI: 24.5% to 55.8%) after POEM and 16.8% (95% CI: 10.2% to 26.4%) after LHM, respectively. The rate of esophagitis after POEM was 29.4% (95% CI: 18.5% to 43.3%) after POEM and 7.6% (95% CI: 4.1% to 13.7%) after LHM. At meta-regression, heterogeneity was explained partly by the POEM approach and study population. The authors concluded that the incidence of reflux disease appeared to be significantly more frequent after POEM than after LHM with fundoplication. Monitoring pH and ensuring appropriate treatment after POEM should be considered in order to prevent long-term reflux-related adverse events.
Cho and Kim (2018) noted that POEM is an endoluminal procedure that involves dissection of esophageal muscle fibers followed by submucosal tunneling. Inoue first attempted to use POEM for the treatment of achalasia in humans. Expanded indications of POEM include classic indications such as type I, type II, type III achalasia, failed prior treatments including botulinum toxin injection, endoscopic balloon dilation, laparoscopic Heller myotomy, and hypertensive motor disorders such as diffuse esophageal spasm and jackhammer esophagus. Contraindications include prior radiation therapy to the esophagus and prior extensive esophageal mucosal resection/ablation involving the POEM field. Most of the complications are minor and self-limited and can be managed conservatively. As POEM emerged as the main treatment for achalasia, various adaptations to tunnel endoscopic surgery have been attempted. Tunnel endoscopic surgery includes POEM, peroral endoscopic tumor resection, and gastric peroral endoscopic pyloromyotomy. The authors concluded that POEM is a safe and effective option for treating type I, type II, type III achalasia, and even for specific cases such as achalasia with failed prior treatments, botulinum toxin injection, endoscopic balloon dilation, LHM, and hypertensive motor disorders. However, they stated that large-scale studies and long-term outcomes are needed; POEM has expanded the scope of adaptation to tunnel endoscopic surgeries such as POET and G-POEM, which also require larger scale studies with long-term outcomes.
van Lennep et al. (2018) stated that achalasia is a rare esophageal motility disorder. Much of the literature is based on the adult population. In adults, guidance of therapeutic approach by manometric findings has led to improvement in patient outcomes. Promising results have been achieved with novel therapies such as POEM. In this review, we provide an overview of the novel diagnostic and therapeutic tools for achalasia management and in what way they will relate to the future management of pediatric achalasia. These investigators performed a PubMed and Embase search of English literature on achalasia using the keywords "children," "achalasia," "pneumatic dilation," "myotomy," and "POEM." Cohort studies of fewer than 10 cases and studies describing patients greater than or equal to 20 years were excluded. Data regarding patient characteristics, treatment outcomes, and adverse events (AEs) were extracted and presented descriptively or pooled when possible. The authors concluded that available data reported that pneumatic dilation and laparoscopic Heller's myotomy are effective in children, with certain studies suggesting lower success rates in pneumatic dilation; POEM is increasingly used in the pediatric setting with promising short-term results; moreover, gastro-esophageal reflux disease (GERD) may occur post-achalasia intervention due to disruption of the LES and therefore requires diligent follow-up, especially in children treated with POEM.
Yeung et al. (2018) noted that experience with POEM for the treatment of achalasia in the pediatric population is limited, with varying techniques in different centers. The accurate extent of submucosal tunneling into the gastric cardia and the adequacy of myotomy are important determining factors for the success of POEM. A majority of studies in the pediatric population have described using submucosal dye injection for assessing the adequacy of myotomy; however, this is a rather crude and inaccurate method. These investigators described the first case of pediatric achalasia managed with POEM incorporated with novel combined techniques using EndoFLIP (Endoluminal Functional Lumen Imaging Probe) and double endoscope. The esophagogastric junction (EGJ) was identified with a gastroscope. Before POEM, EndoFLIP showed an EGJ distensibility index of 1.7 mm²/mmHg. A submucosal tunnel was created from the mucosal entry site at mid-esophagus down and approximately 3 cm beyond the EGJ. Anterior myotomy cutting the circular muscle layer while preserving the longitudinal muscle was performed for 8 cm. The double-endoscope technique was used to confirm the adequacy of myotomy by inserting a smaller endoscope through the nostril into the stomach and observing the trans-illumination of the first endoscope at the end of the submucosal tunnel. After POEM, repeat EndoFLIP measurements revealed an increased distensibility index to 6.0 mm²/mmHg. Endoscopic examination at the end of the procedure showed a widely patent EGJ. The Eckardt symptoms score improved from 9 to 0. At 7 months after POEM, esophagoscopy showed a widely open EGJ with no esophagitis, and high-resolution esophageal manometry revealed normalized lower esophageal sphincter pressure and resting tone. The authors concluded that they introduced the intra-operative use of the EndoFLIP system that allowed real-time assessment of EGJ distensibility and immediate treatment effect evaluation. Incorporation of double-endoscope POEM was also first described in this pediatric patient for ensuring complete gastric myotomy. They stated that from their experiences, POEM for achalasia in the pediatric population appeared to have encouraging results similar to those in adult patients.
In an update of the clinical practice from the American Gastroenterological Association (AGA) on "The use of per-oral endoscopic myotomy in achalasia," Kahrilas and colleagues (2017) described a place for per-oral endoscopic myotomy (POEM) among the currently available robust treatments for achalasia. The recommendations outlined were based on expert opinion and on relevant publications from PubMed and Embase. The Clinical Practice Updates Committee of the AGA proposed the following recommendations: First, in determining the need for achalasia therapy, patient-specific parameters (Chicago Classification subtype, comorbidities, early vs. late disease, primary or secondary causes) should be considered along with published efficacy data; second, given the complexity of this procedure, POEM should be performed by experienced physicians in high-volume centers because an estimated 20 to 40 procedures are needed to achieve competence; third, if the expertise is available, POEM should be considered as primary therapy for type III achalasia; fourth, if the expertise is available, POEM should be considered as a treatment option comparable with laparoscopic Heller myotomy for any of the achalasia syndromes; and fifth, post-POEM patients should be considered high-risk for developing reflux esophagitis and advised of the management considerations (potential indefinite proton pump inhibitor therapy and/or surveillance endoscopy) of this before undergoing the procedure.
In a review on "Current treatment of achalasia," von Rahden (2019) stated that advantages of POEM include the possibility to perform a long myotomy (of the entire length of the esophagus if necessary) and the relatively free choice of the localization of the myotomy (anterior/posterior POEM). The disadvantage is the increased post-operative gastroesophageal reflux disease (GERD) following POEM; however, this sequel is managed with proton pump inhibitors (PPIs) in most cases, or a laparoscopic fundoplication if necessary. Preliminary results of 2 prospective, randomized trials showed the superiority of POEM over endoscopic pneumatic dilation (PD), as well as the non-inferiority to laparoscopic Heller myotomy (LHM), but increased post-operative GERD. The author uses a tailored approach, with preference for POEM for achalasia type III and type II with chest pain, and LHM + Dor procedure for sigmoid achalasia and other associated morphological changes.
Zaninotto and associates (2019) evaluated the efficacy, morbidity, and side effects of innovative management strategies for achalasia that include high-resolution manometry (HRM), pneumatic dilatation, laparoscopic Heller's myotomy (LHM), injection of botulinum toxin (BTX) into the LES, and POEM. High-resolution manometry has enabled identification of achalasia subtypes that have important prognostic implications. Pneumatic dilatation is a commonly used and cost-effective method of treating achalasia but has shown poor longevity of symptom relief compared with other modalities and carries a risk of esophageal perforation. LHM is often the preferred, most effective treatment modality; however, new studies may show that outcomes are equivalent or even inferior to POEM. BTX injection of the LES has a waning and short duration of efficacy and is used primarily for patients unsuitable for more definitive invasive procedures. POEM is considered the most effective treatment for type III achalasia but carries a high risk of iatrogenic GERD that might predispose to the development of Barrett's esophagus. The authors concluded that HRM and POEM are two major innovations in the management of achalasia developed over the past 10 years. There are now three major management options for patients with achalasia, namely pneumatic dilatation, LHM, and POEM.
Werner et al. (2019) noted that pneumatic dilation and laparoscopic Heller's myotomy (LHM) are established treatments for idiopathic achalasia. Per-oral endoscopic myotomy (POEM) is a less invasive therapy with promising early study results. In a randomized, multi-center study, these researchers compared POEM with LHM plus Dor's fundoplication in patients with symptomatic achalasia. The primary endpoint was clinical success, defined as an Eckardt symptom score of 3 or less (range of 0 to 12, with higher scores indicating more severe symptoms of achalasia) without the use of additional treatments at the 2-year follow-up; a non-inferiority margin of -12.5 percentage points was used in the primary analysis. Secondary endpoints included adverse events (AEs), esophageal function, Gastrointestinal Quality of Life Index score (range of 0 to 144, with higher scores indicating better function), and gastroesophageal reflux (GER). A total of 221 patients were randomly assigned to undergo either POEM (112 patients) or LHM plus Dor's fundoplication (109 patients). Clinical success at the 2-year follow-up was observed in 83.0% of patients in the POEM group and 81.7% of patients in the LHM group (difference, 1.4 percentage points; 95% confidence interval [CI]: -8.7 to 11.4; p = 0.007 for non-inferiority). Serious AEs occurred in 2.7% of patients in the POEM group and 7.3% of patients in the LHM group. Improvement in esophageal function from baseline to 24 months, as assessed by measurement of the integrated relaxation pressure of the lower esophageal sphincter (LES), did not differ significantly between the treatment groups (difference, -0.75 mm Hg; 95% CI: -2.26 to 0.76), nor did improvement in the score on the Gastrointestinal Quality of Life Index (difference, 0.14 points; 95% CI: -4.01 to 4.28). At 3 months, 57% of patients in the POEM group and 20% of patients in the LHM group had reflux esophagitis, as assessed by endoscopy; at 24 months, the corresponding percentages were 44% and 29%. The authors concluded that POEM was non-inferior to LHM plus Dor's fundoplication in controlling symptoms of achalasia at 2 years; however, GER was more common among patients who underwent POEM than among those who underwent LHM.
The authors stated that this study had several drawbacks. Less than 50% of the eligible patients participated in the trial, mainly because of a lack of patient consent to undergo randomization. The surgeons were more experienced in performing LHM plus Dor’s fundoplication than the endoscopists were in performing POEM. These researchers did not analyze treatment effects on post-operative pain or on the use of pain medications; in general, the findings at the 2-year follow-up in this study suggested that there was no between-group difference in improvements in patient-reported quality of life (QOL). Patients and trial personnel were aware of the treatment-group assignments because blinding was not possible. This was a potential source of bias given that the primary endpoint was based on patients’ reports of symptoms; however, objective assessment by manometry corroborated the primary finding.
Vaezi et al. (2020) stated that achalasia is an esophageal motility disorder characterized by aberrant peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). Patients most commonly present with dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. High-resolution manometry has identified 3 subtypes of achalasia distinguished by pressurization and contraction patterns. Endoscopic findings of retained saliva with puckering of the gastroesophageal junction or esophagram findings of a dilated esophagus with bird beaking are important diagnostic clues. In an American College of Gastroenterology (ACG) guideline, the authors used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process to provide clinical guidance on how best to diagnose and treat patients with achalasia. They stated that “We suggest that POEM or PD result in comparable symptomatic improvement in patients with types I or II achalasia – Low GRADE quality; and “conditional” recommendation.”
In a systematic review and network meta-analysis, Facciorusso and colleagues (2021) examined the comparative efficacy of different strategies for the management of achalasia. These researchers identified 6 randomized controlled trials (RCTs) in adults with achalasia that compared the efficacy of pneumatic dilation (PD; n = 260), laparoscopic Heller myotomy (LHM; n = 309), and per-oral endoscopic myotomy (POEM; n = 176). The primary efficacy outcome was 1-year treatment success (patient-reported improvement in symptoms based on validated scores); secondary efficacy outcomes were 2-year treatment success and physiologic improvement; safety outcomes were the risk of gastroesophageal reflux disease (GERD), severe erosive esophagitis, and procedure-related serious adverse events (SAEs). These investigators performed pair-wise and network meta-analysis for all treatments and used GRADE criteria to appraise the quality of evidence. Low-quality evidence, based primarily on direct evidence, supports the use of POEM (RR [risk ratio], 1.29; 95% confidence intervals [CI]: 0.99 to 1.69) and LHM (RR, 1.18 [0.96 to 1.44]) over PD for treatment success at 1 year; no significant difference was observed between LHM and POEM (RR 1.09 [0.86 to 1.39]). The incidence of severe esophagitis after POEM, LHM, and PD was 5.3%, 3.7%, and 1.5%, respectively. The procedure-related SAE rate after POEM, LHM, and PD was 1.4%, 6.7%, and 4.2%, respectively. The authors concluded that POEM and LHM have comparable efficacy and may increase treatment success compared to PD with low confidence in estimates. POEM may have a lower rate of SAEs compared to LHM and PD, but a higher rate of GERD. Moreover, these researchers stated that future prospective studies comparing the long-term safety and efficacy of POEM, LHM, and PD, particularly across specific achalasia subtypes, are needed.
The authors stated that this study had several drawbacks. First, only retrospective and prospective studies were included. No RCTs were found. Second, owing to the paucity of data in the included studies, these researchers were unable to evaluate the safety and efficacy of POEM for patients with previous surgical or endoscopic interventions separately. Third, some studies included pediatric patients with achalasia and some patients with other esophageal dysmotility disorders. However, these patients accounted for a small percentage, and the outcomes were unchanged after removing these studies. Fourth, these investigators were unable to examine the quality of life (QOL) in patients with prior treatments after POEM due to the limited number of studies reporting these findings. Last, long-term (greater than 2 years) differences between the patients with and without prior intervention should be interpreted carefully as only 2 studies reported these outcomes.
Dirks et al. (2021) examined the literature comparing POEM to Heller myotomy (HM) and pneumatic dilation (PD) for the treatment of achalasia. These researchers carried out a systematic review of comparative studies between POEM and HM or PD. A priori outcomes pertained to efficacy, perioperative metrics, and safety. The internal validity of observational studies and randomized controlled trials (RCTs) was judged using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2.0 tool, respectively. From 1,379 unique literature citations, these investigators included 28 studies comparing POEM and HM (n = 21) or PD (n = 8), with only 1 RCT addressing each. Aside from two 4-year observational studies, POEM follow-up averaged less than or equal to 2 years. While POEM had similar efficacy to HM, POEM treated dysphagia better than PD both in an RCT (treatment "success" RR 1.71, 95% CI: 1.34 to 2.17; 126 patients) and in observational studies (Eckardt score MD -0.43, 95% CI: -0.71 to -0.16; 5 studies; I² 21%; 405 patients). POEM needed re-intervention less than PD in an RCT (RR 0.19, 95% CI: 0.08 to 0.47; 126 patients) and HM in an observational study (RR 0.33, 95% CI: 0.16 to 0.68; 98 patients). Though 6 to 12 months patient-reported reflux was worse than PD in 3 observational studies (RR 2.67, 95% CI: 1.02 to 7.00; I² 0%; 164 patients), post-intervention reflux was inconsistently measured and not statistically different in measures greater than or equal to 1 year. POEM had similar safety outcomes to both HM and PD, including treatment-related serious AEs. The authors concluded that POEM has similar outcomes to HM and greater efficacy than PD; however, reflux remains a critical outcome with unknown long-term clinical significance due to insufficient data and inconsistent reporting.
Zhong et al. (2021) stated that POEM is a novel minimally invasive intervention in treating achalasia in adults. Presently, POEM has also been reported to be effective for achalasia in children. These researchers examined the clinical outcomes of POEM for pediatric achalasia. They carried out a systematic literature search in PubMed, Embase, and Cochrane databases, which covered the period from January 2009 to June 2020. Selecting studies and collecting data was done independently by 2 reviewers according to pre-defined criteria. The statistical analysis was conducted using Comprehensive Meta-Analysis software version 2 and Review Manager 5.3. A total of 11 studies with 389 children were identified in the final analysis. Pooled technical success of POEM treatment for achalasia was achieved in 385 children (97.4%; 95% CI: 94.7% to 98.7%), and the pooled clinical success was achieved in 348 children (92.4%; 95% CI: 89.0% to 94.8%). After POEM, the Eckardt score was significantly decreased by 6.76 points (95% CI: 6.18 to 7.34, p < 0.00001), and the LES pressure was significantly reduced by 19.38 mmHg (95% CI: 17.54 to 21.22, p < 0.00001). The pooled major AEs rate related to POEM was 12.8% (95% CI: 4.5% to 31.5%) and the GER rate was 17.8% (95% CI: 14.2% to 22.0%). The authors concluded that the current study demonstrated that POEM was a safe and effective technique for treating achalasia in children. Moreover, they stated that further randomized comparative studies of POEM and other therapeutic methods are needed to determine the most effective treatment modality for achalasia in children.
An AGA Clinical Practice Update (2024) states that POEM, laparoscopic Heller myotomy (LHM), and pneumatic dilation (PD) are also effective therapies for type I and type II achalasia, and that the choice should be based on shared decision-making (Yang, et al., 2024). ACG Clinical Guidelines similarly support POEM for all achalasia subtypes (Vaezi et al., 2020).
POEM for the Treatment of Non-Achalasia Spastic Esophageal Motility Disorders
Familiari et al. (2024) stated that non-achalasia esophageal motility disorders (NAOMD) represent a heterogeneous group of rare diseases, including esophagogastric junction outflow obstruction, distal esophageal spasm, and hyper-contractile esophagus. Despite the differing etiological, manometric and pathophysiological characteristics, these disorders are unified by similar clinical presentation, including dysphagia and chest pain. The management of these disorders remain a challenge for the clinician. Pharmacotherapy, BTX injection, endoscopic dilation, as well as laparoscopic Heller myotomy have been used, with limited effectiveness in the majority of patients. To-date, there are no controlled studies that suggested which is the best approach for the management of these diseases. Since its introduction in clinical practice, POEM has emerged as a very promising, minimally invasive and effective treatment for esophageal achalasia. No longer after the first uses, POEM has been successfully employed also for the management of selected patients with NAOMD; however, currently available data are limited by small sample sizes and short-term follow-up. These investigators stated that the diagnosis of NAOMD needs to be confirmed by a gastroenterologist expert of esophageal motility disorders; and POEM is a promising therapeutic option for NAOMD, and should only be performed in patients with severe dysphagia, associated with substantial weight loss, after the failure of medical therapy at long-term; and should be carried out in high-volume centers. Moreover, these researchers stated that prospective, multi-center studies, including a large population, are needed to examine the effectiveness of POEM in various NAOMD. In particular, randomized studies versus surgery or other medical or endoscopic interventions could better define the role of POEM in the management of NAOMD.
Transcutaneous Gastric Pacing for Gastro-Intestinal Motility Recovery and Inflammation Improvement in Early-Stage Acute Pancreatitis Patients
Jia et al. (2024) stated that acute pancreatitis (AP) is frequently accompanied by GI motility disorders. These investigators examined the effectiveness and possible mechanism of transcutaneous gastric pacing (TGP) in early-stage AP patients. A total of 65 AP patients were randomly divided into conventional treatment group and TGP group. The serum ghrelin and vasoactive intestinal peptide (VIP) were used to examine the possible GI hormonal mechanism involved. The parameters of electrogastrogram (EGG) were employed to assess the gastric motility in AP patients. The 1st defecation time was used to evaluate the recovery of intestinal motility. The heart rate variability (HRV) test was carried out to examine autonomic nervous function. Compared with the conventional treatment group, the TGP treatment significantly improved symptoms in early AP patients, and shortened the 1st defecation time (p < 0.05) and the hospital days (p < 0.05). The level of VIP (p < 0.05) was also decreased in TGP group. The percentage of normal gastric slow waves (GSWS) (p < 0.05) was increased. The interleukin (IL)-6 level was decreased (p < 0.05). Concurrently, the vagal activity (high-frequency [HF]) was increased (p < 0.01), the sympathetic activity low-frequency [(LF]) was decreased (p < 0.01), and the ratio of sympathetic vagal (LF/HF) was decreased (p < 0.01). The authors concluded that TGP treatment significantly improved the clinical symptoms in early AP patients. It also increased the percentage of normal GSWS. The therapeutic effect of TGP may be caused by autonomic nervous function mechanisms. Moreover, these researchers stated that although this trial demonstrated promising clinical results, further investigations are needed to ascertain the mechanisms by which TGP improves GI motility, the GI hormones, and inflammation in AP patients.
The authors stated that this study had several drawbacks. First, these investigators enrolled the early AP patients, which could not cover the whole course of pancreatitis. Second, these researchers included patients with mild AP (MAP) and moderately severe AP (MSAP), but did not cover severe AP (SAP) patients; thus, whether TGP was effective in SAP need further investigations. Third, the authors did not monitor the GI motility and inflammatory factors further; thus, it was unclear how these indicators change during the TGP interval. Due to the limitations of objective conditions, they did not test other GI hormone indexes, other relevant markers of GI function, like intestinal permeability or other motility indices; thus, these investigators could not fully assess the therapeutic effect of TGP. Fourth, TGP shortened the 1st defecation time and improved intestinal motility; however, there was a lack of more detailed indicators to evaluate. Fifth, the relatively small sample size (n = 65) posed challenges in the generalizability of the outcomes, as findings might not accurately reflect broader patient demographics. Furthermore, the inter-group differences were not very significant in inflammatory factors and EGG parameters. Further expanding the sample size might enable the authors to observe the therapeutic advantages of TGP more comprehensively and obtain more convincing research conclusions. Sixth, the lack of blinding in the study design. Due to the lack of a sham-TGP treatment group, this prevented the authors from carrying out a blind study. The subjective factors of enrolled patients might affect the reliability of the conclusions drawn from this study, which might result in certain bias in the study findings. In the follow-up study, these researchers would add sham-TGP therapy to reduce the influence of subjective factors on the results. Seventh, this was a preliminary study, and in the future, these investigators will add more reliable animal experimental studies as well as clinical studies to verify the optimal parameters and mechanism of TGP.
References
The above policy is based on the following references:
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Gastric Pacing and Gastric Electrical Stimulation for Gastro-Intestinal Dysmotility
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Gastric Pacing and Gastric Electrical Stimulation for Cyclic Vomiting Syndrome and Selected Indications
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Gastric Per-Oral Endoscopic Myotomy
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- Rodriguez J, Strong AT, Haskins IN, et al. Per-oral pyloromyotomy (POP) for medically refractory gastroparesis: Short term results from the first 100 patients at a high volume center. Ann Surg. 2018;268(3):421-430.
- Shen S, Luo H, Vachaparambil C, et al. Gastric peroral endoscopic pyloromyotomy versus gastric electrical stimulation in the treatment of refractory gastroparesis: A propensity score-matched analysis of long term outcomes. Endoscopy. 2020;52(5):349-358.
- Shlomovitz E, Pescarus R, Cassera MA, et al. Early human experience with per-oral endoscopic pyloromyotomy (POP). Surg Endosc. 2015;29(3):543-551.
- Spadaccini M, Maselli R, Chandrasekar VT, et al. Gastric peroral endoscopic pyloromyotomy for refractory gastroparesis: A systematic review of early outcomes with pooled analysis. Gastrointest Endosc. 2020;91(4):746-752.
- Tao J, Patel V, Mekaroonkamol P, et al. Technical aspects of peroral endoscopic pyloromyotomy. Gastrointest Endosc Clin N Am. 2019;29(1):117-126.
- Uemura KL, Chaves D, Bernardo WM, et al. Peroral endoscopic pyloromyotomy for gastroparesis: A systematic review and meta-analysis. Endosc Int Open. 2020;8(7):E911-E923.
- Usai-Satta P, Bellini M, Morelli O, et al. Gastroparesis: New insights into an old disease. World J Gastroenterol. 2020;26(19):2333-2348.
- Weusten BLAM, Barret M, Bredenoord AJ, et al. Endoscopic management of gastrointestinal motility disorders - part 1: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020;52(6):498-515.
- Xu J, Chen T, Elkholy S, et al. Gastric peroral endoscopic myotomy (G-POEM) as a treatment for refractory gastroparesis: Long-term outcomes. Can J Gastroenterol Hepatol. 2018;2018:6409698.
- Yan J, Tan Y, Zhou B, et al. Gastric per-oral endoscopic myotomy (G-POEM) is a promising treatment for refractory gastroparesis: A systematic review and meta-analysis. Rev Esp Enferm Dig. 2020;112(3):219-228.
- Zhang H, Zhang J, Jiang A, Ni H. Gastric peroral endoscopic myotomy for gastroparesis: A systematic review of efficacy and safety. Gastroenterol Hepatol. 2019;42(7):413-422.
Diverticular Peroral Endoscopic Myotomy (D-POEM) / Zenker POEM (Z-POEM) Diverticulotomy
- Al Ghamdi SS, Farha J, Moran RA, et al. Zenker's peroral endoscopic myotomy, or flexible or rigid septotomy for Zenker's diverticulum: A multicenter retrospective comparison. Endoscopy. 2022;54(4):345-351.
- Buyruk AM, Erdogan C. Efficacy and safety of peroral endoscopic myotomy in the treatment of Zenker's diverticulum: A single-center experience. Turk J Gastroenterol. 2024;35(2):119-124.
- Desai PN, Kabrawala MV, Patel CN, et al. Z-POEM as a treatment option for Zenker’s diverticulum: Our experience at a tertiary care centre in India. J Dig Endosc. 2020;11(03):209-214.
- Elkholy S, El-Sherbiny M, Delano-Alonso R, et al. Peroral endoscopic myotomy as treatment for Zenker's diverticulum (Z-POEM): A multi-center international study. Esophagus. 2021 Jul;18(3):693-699.
- Feußner H, Hüser N, Wilhelm D, et al. Surgical treatment of esophageal diverticula: Endoscopic or open approach? Chirurg. 2017;88(3):196-203.
- Kahaleh M, Mahpour NY, Tyberg A, et al. Per oral endoscopic myotomy for Zenker's diverticulum: A novel and superior technique compared with septotomy? J Clin Gastroenterol. 2022;56(3):224-227.
- Klingler MJ, Landreneau JP, Strong AT, et al. Endoscopic mucosal incision and muscle interruption (MIMI) for the treatment of Zenker's diverticulum. Surg Endosc. 2021;35(7):3896-3904.
- Mandavdhare HS, Kumar MP, Jha D, et al. Diverticular per oral endoscopic myotomy (DPOEM) for esophageal diverticular disease: A systematic review and meta-analysis. Esophagus. 2021;18(3):436-450.
- Maydeo A, Patil GK, Dalal A. Operative technical tricks and 12-month outcomes of diverticular peroral endoscopic myotomy (D-POEM) in patients with symptomatic esophageal diverticula. Endoscopy. 2019;51(12):1136-1140.
- Samanta J, Mandavdhare HS, Kumar N, et al. Per oral endoscopic myotomy for the management of large esophageal diverticula (D-POEM): Safe and effective modality for complete septotomy. Dysphagia. 2022;37(1):84-92.
- Sato H, Takeuchi M, Hashimoto S, et al. Esophageal diverticulum: New perspectives in the era of minimally invasive endoscopic treatment. World J Gastroenterol. 2019 8;25(12):1457-1464.
- Stasek M, Neoral C, Zhydkov R, et al. Current possibilities of minimally invasive therapy of oesophageal diverticula. Rozhl Chir. 2020;99(4):152-158.
- Swei E, Pokala SK, Menard-Katcher P, Wagh MS. Comparison of Zenker's per-oral endoscopic myotomy (Z-POEM) with standard flexible endoscopic septotomy for Zenker's diverticulum: A prospective study with 2-year follow-up. Surg Endosc. 2023;37(9):6818-6823.
- Yang J, Zeng X, Yuan X, et al. An international study on the use of peroral endoscopic myotomy (POEM) in the management of esophageal diverticula: The first multicenter D-POEM experience. Endoscopy. 2019;51(4):346-349.
- Zeng X, Bai S, Zhang Y, et al. Peroral endoscopic myotomy for the treatment of esophageal diverticulum: An experience in China. Surg Endosc. 2021;35(5):1990-1996.
- Zhang H, Huang S, Xia H, et al. The role of peroral endoscopic myotomy for Zenker's diverticulum: A systematic review and meta-analysis. Surg Endosc. 2022;36(5):2749-2759.
Per-Oral Endoscopic Myotomy for Achalasia
- Awaiz A, Yunus RM, Khan S, et al. Systematic review and meta-analysis of perioperative outcomes of peroral endoscopic myotomy (POEM) and laparoscopic Heller myotomy (LHM) for achalasia. Surg Laparosc Endosc Percutan Tech. 2017;27(3):123-131.
- Banks M, Sweis R. POEM and the management of achalasia. Frontline Gastroenterol. 2017;8(2):143-147.
- Bredenoord AJ, Rösch T, Fockens P. Peroral endoscopic myotomy for achalasia. Neurogastroenterol Motil. 2014;26(1):3-12.
- Cappell MS, Stavropoulos SN, Friedel D, et al. Updated systematic review of achalasia, with a focus on POEM therapy. Dig Dis Sci. 2020;65(1):38-65.
- Cho YK, Kim SH. Current status of peroral endoscopic myotomy. Clin Endosc. 2018 ;51(1):13-18.
- Crespin OM, Liu LWC, Parmar A, et al. Safety and efficacy of POEM for treatment of achalasia: A systematic review of the literature. Surg Endosc. 2017;31(5):2187-2201.
- Dirks RC, Kohn GP, Slater B, et al. Is peroral endoscopic myotomy (POEM) more effective than pneumatic dilation and Heller myotomy? A systematic review and meta-analysis. Surg Endosc. 2021;35(5):1949-1962.
- Facciorusso A, Singh S, Fehmi SMA, et al. Comparative efficacy of first-line therapeutic interventions for achalasia: A systematic review and network meta-analysis. Surg Endosc. 2021;35(8):4305-4314.
- Hernandez Mondragon OV, Gonzalez Martinez MA, Blancas Valencia JM, et al. Long-term quality of life after peroral endoscopic myotomy remains compromised in patients with achalasia type III. Endoscopy. 2017;49(12):1209-1218.
- Huang Z, Cui Y, Li Y, et al. Peroral endoscopic myotomy for achalasia patients with prior Heller myotomy: A systematic review and meta-analysis. Gastrointest Endosc. 2021;93(1):47-56.
- Kahrilas PJ, Katzka D, Richter JE. Clinical practice update: The use of per-oral endoscopic myotomy in achalasia: Expert review and best practice advice from the AGA Institute. Gastroenterology. 2017;153(5):1205-1211.
- Kroch DA, Grimm IS. POEM for achalasia. Am Surg. 2018;84(4):489-495.
- Liu W, Zeng HZ, Chen HL, et al. Open peroral endoscopic myotomy (O-POEM) for the treatment of achalasia. Dis Esophagus. 2017;30(10):1-2.
- Martins RK, Ribeiro IB, De Moura DTH, et al. Peroral (POEM) or surgical myotomy for the treatment of achalasia: A systematic review and meta-analysis. Arq Gastroenterol. 2020;57(1):79-86.
- Nabi Z, Ramchandani M, Chavan R, et al. Per-oral endoscopic myotomy for achalasia cardia: Outcomes in over 400 consecutive patients. Endosc Int Open. 2017;5(5):E331-E339.
- Pescarus R, Shlomovitz E, Swanstrom LL. Per-oral endoscopic myotomy (POEM) for esophageal achalasia. Curr Gastroenterol Rep. 2014;16(1):369.
- Repici A, Fuccio L, Maselli R, et al. GERD after per-oral endoscopic myotomy as compared with Heller's myotomy with fundoplication: A systematic review with meta-analysis. Gastrointest Endosc. 2018;87(4):934-943.
- Schlottmann F, Luckett DJ, Fine J, et al. Laparoscopic Heller myotomy versus peroral endoscopic myotomy (POEM) for achalasia: A systematic review and meta-analysis. Ann Surg. 2018;267(3):451-460.
- Schlottmann F, Patti MG. Laparoscopic Heller myotomy versus per oral endoscopic myotomy: Evidence-based approach to the treatment of esophageal achalasia. Am Surg. 2018;84(4):496-500.
- Tan S, Zhong C, Ren Y, et al. Efficacy and safety of peroral endoscopic myotomy in achalasia patients with failed previous intervention: A systematic review and meta-analysis. Gut Liver. 2021;15(2):153-167.
- Vaezi MF, Pandolfino JE, Yadlapati RH, et al. ACG Clinical Guidelines: Diagnosis and management of achalasia. Am J Gastroenterol. 2020;115(9):1393-1411.
- van Lennep M, van Wijk MP, Omari TIM, et al. Clinical management of pediatric achalasia. Expert Rev Gastroenterol Hepatol. 2018;12(4):391-404.
- von Rahden BHA. Current treatment of achalasia 2019. Zentralbl Chir. 2019;144(2):163-170.
- Werner YB, Hakanson B, Martinek J, et al. Endoscopic or surgical myotomy in patients with idiopathic achalasia. N Engl J Med. 2019;381(23):2219-2229.
- Yang D, Bechara R, Dunst CM, Konda VJA. AGA Clinical Practice Update on Advances in Per-Oral Endoscopic Myotomy (POEM) and Remaining Questions-What We Have Learned in the Past Decade: Expert Review. Gastroenterology. 2024;167(7):1483-1490.
- Yeung F, Wong IYH, Chung PHY, et al. Peroral endoscopic myotomy with EndoFLIP and double-endoscope: Novel techniques for achalasia in pediatric population. J Laparoendosc Adv Surg Tech A. 2018 28(3):343-347.
- Zaninotto G, Leusink A, Markar SR. Management of achalasia in 2019. Curr Opin Gastroenterol. 2019;35(4):356-362.
- Zhong C, Tan S, Huang S, et al. Clinical outcomes of peroral endoscopic myotomy for achalasia in children: A systematic review and meta-analysis. Dis Esophagus. 2021;34(4):doaa112.
Miscellaneous Indications
- Familiari P, Mangiola F, Parmigiani M, Landi R. POEM for non-achalasia spastic oesophageal motility disorders. Best Pract Res Clin Gastroenterol. 2024;71:101909.
- Farooq A, Fawwaz BB, Zhang Y, et al. Prospective analysis of endoscopic impedance planimetry pyloric measurements and its association with clinical outcomes with gastric peroral endoscopic myotomy. Endoscopy. 2025 May 22 [Online ahead of print].
- Gantuya B, Inoue H, Yamamoto K, et al. Role of balloon dilation test in identifying suitable candidates for gastric peroral endoscopic myotomy. DEN Open. 2025;5(1):e70049.
- Jia Z, Kong L, Lu X, et al. The mechanism of transcutaneous gastric pacing treatment on gastrointestinal motility recovery and inflammation improvement in early-stage acute pancreatitis patients. BMC Gastroenterol. 2024;24(1):407.
- Varghese C, Lim A, Daker C, et al; BSM Consortium and GPOEM-GEMS Study Group. Predictors of outcomes after gastric peroral endoscopic myotomy for refractory gastroparesis: A systematic review. Am J Gastroenterol. 2024;120(6):1275-1284.
- Williams AE, Bhanat E, Seerapu VN, et al. Gastric peroral pyloromyotomy effectiveness in management of all types of gastroparesis. J Gastrointest Surg. 2025;29(6):102031.
