Gastric Pacing / Electrical Stimulation and Gastroesophageal Per Oral Endoscopic Myotomy

Number: 0678

Policy
Applicable 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.

Medical Necessity

Aetna considers the following medically necessary:
1. 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 to medical management (including dietary modification, antiemetics, and prokinetics);
2. Revision or replacement of a previously approved gastric stimulator implant for complications associated with gastric pacing (eg, bowel obstruction, gastric wall perforation, infection, lead dislodgement or lead erosion into the small intestine).
3. Per-oral endoscopic myotomy for the treatment of Zenker diverticulum;
4. Gastric per-oral endoscopic myotomy (G-POEM) for members with severe gastroparesis who meet all of the following criteria:
  1. 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
  2. Symptom duration has been greater than 6 months; and
  3. 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).
Experimental and Investigational

Aetna considers the following procedures experimental and investigational because the effectiveness of these approaches has not been established:
1. Gastric per-oral endoscopic myotomy (G-POEM) for treatment of congenital hypertrophic pyloric stenosis and all other indications (except for the one listed above);
2. Temporary gastric electrical stimulation (GES) for the prediction of success of GES in the treatment of gastroparesis;
3. 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 and investigational.
Related Policies
- CPB 0061 - Nutritional Support
- CPB 0113 - Botulinum Toxin
- CPB 0213 - Gastroesophageal Reflux Disease (GERD): Treatment Devices
- CPB 0396 - Gastrointestinal Function: Selected Tests
- CPB 0625 - Dysphagia Therapy - for the use of POEM in the treatment of type III (spastic) achalasia

Table:
CPT Codes / HCPCS Codes / ICD-10 Codes
Code	Code Description
CPT codes covered if selection criteria are met:
43180	Esophagoscopy, rigid, transoral with diverticulectomy of hypopharynx or cervical esophagus (eg, Zenker's diverticulum), with cricopharyngeal myotomy, includes use of telescope or operating microscope and repair, when performed
43497	Lower esophageal myotomy, transoral (ie, peroral endoscopic myotomy [POEM])
43647	Laparoscopy, surgical; implantation or replacement of gastric neurostimulator electrodes, antrum
43648	revision or removal of gastric neurostimulator electrodes, antrum
43881	Implantation or replacement of gastric neurostimulator electrodes, antrum, open
43882	Revision or removal of gastric neurostimulator electrodes, antrum, open
64590	Insertion or replacement of peripheral or gastric neurostimulator pulse generator or receiver, direct or inductive coupling
64595	Revision or removal of peripheral or gastric neurostimulator pulse generator or receiver
95980	Electronic analysis of implanted neurostimulator pulse generator system (e.g., rate, pulse amplitude and duration, configuration of wave form, battery status, electrode selectability, output modulation, cycling, impedance and patient measurements) gastric neurostimulator pulse generator/transmitter; intraoperative, with programming
95981	subsequent, without reprogramming
95982	subsequent, with reprogramming
CPT codes not covered for indications listed in the CPB:
Diverticular peroral endoscopic myotomy (D-POEM), temporary gastric electrical stimulation (GES) - no specific code:
Other CPT codes related to the CPB:
78264	Gastric emptying imaging study (eg, solid, liquid, or both)
78265	Gastric emptying imaging study (eg, solid, liquid, or both); with small bowel transit
78266	Gastric emptying imaging study (eg, solid, liquid, or both); with small bowel and colon transit, multiple days
HCPCS codes covered if selection criteria are met:
C1767	Generator, neurostimulator (implantable), non-rechargeable
C1778	Lead, neurostimulator (implantable)
L8679	Implantable neurostimulator pulse generator, any type
L8680	Implantable neurostimulator electrode, each
L8688	Implantable neurostimulator pulse generator, dual array, non-rechargeable, includes extension
ICD-10 codes covered if selection criteria are met:
E08.43 E09.43 E10.43 E11.43 E13.43 [K31.84 also required]	Diabetic gastroparesis
K22.5	Diverticulum of esophagus, acquired
K31.84	Gastroparesis
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
E08.00 - E08.42 E08.44 - E09.42 E09.44 - E10.42 E10.44 - E11.42 E11.44 - E13.42 E13.44 - E13.9	Diabetes mellitus
E66.01 - E66.1 E66.8 - E66.9	Obesity and morbid obesity
F50.81 - F50.89	Other eating disorders [psychogenic cyclic vomiting]
G43.A0	Cyclical vomiting, not intractable
G43.A1	Cyclical vomiting, intractable
G90.01 - G90.9, G90.A	Disorders of autonomic nervous system
K30	Functional dyspepsia
Q40.0	Congenital hypertrophic pyloric stenosis

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.

Bortolotti (2002) noted that there are currently 3 principal methods of GES:

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 neurostimulation 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 gastroelectrical 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 comparision 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.

An UpToDate review on “Electrical stimulation for gastroparesis” (Hasler, 2015) states that “Patients with severe nausea and vomiting (occurring on average at least once-daily), which have proven refractory to aggressive anti-emetic and prokinetic drug therapy for at least 1 year in duration may be candidates for gastric neurostimulation. In the United States, the gastric electrical neurostimulator (Enterra Therapy system, Medtronic, Inc., Minneapolis, MN) has been approved as a humanitarian exemption device only for diabetic and idiopathic gastroparesis”.

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.

In a prospective, randomized, placebo-controlled, double-blind, multi-center study, Shikora et al (2009) compared IGS therapy with a standard diet and behavioral therapy regimen in a group of class 2 and 3 obese subjects by evaluating the difference in the percentage of excess weight loss (EWL) between the control and treatment groups. The primary endpoint was the percentage of EWL from baseline to 12 months after randomization. A total of 190 subjects were enrolled in this study. All patients underwent implantation with the implantable gastric stimulator and were randomized to one of the following two groups:

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 pressure (LES): 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.

An UpToDate review on “Peroral endoscopic myotomy (POEM)” (Khashab, 2019) states that “Gastric peroral endoscopic myotomy (G-POEM), which is an endoscopic equivalent of surgical pyloroplasty, has been performed in a few centers for severe refractory diabetic gastroparesis … Several case reports show that G-POEM is safe, feasible, and effective in treating severe refractory gastroparesis”.

Furthermore, an UpToDate review on “Treatment of gastroparesis” (Camilleri, 2019) does not mention G-POEM as a therapeutic option.

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 aetiologies.

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.

An UpToDate review on “Treatment of gastroparesis” (Camilleri, 2021) lists gastric per-oral endoscopic myotomy (G-POEM) under “Other therapies with limited or unclear role”. It states that “Randomized sham-controlled trials are required to establish the role of endoscopic approaches (pyloromyotomy, transpyloric stent) and laparoscopic (pyloroplasty) approaches in patients with gastroparesis. Endoscopic placement of a transpyloric stent, which is anchored by suturing on the gastric side, has been evaluated in patients with gastroparesis. In an open-label trial in which a total of 30 patients with refractory gastroparesis underwent 48 transpyloric stent procedures, clinical response was reported in 21 of 28 patients (75 %), with greater efficacy in those with predominant nausea and/or vomiting than in those with predominant pain. Endoscopic pyloromyotomy (gastric per-oral endoscopic myotomy [G-POEM]) and laparoscopic pyloroplasty have been successful in small studies in treating gastroparesis”.

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.

An UpToDate review on “Zenker's diverticulum” (Schiff and van Delft, 2021) states that “Zenker-Peroral endoscopic myotomy (Z-POEM) is a newer flexible endoscopic technique for the management of ZD which is considered the endoscopic equivalent of surgical myotomy. Z-POEM relies on submucosal tunneling to completely expose and dissect the septum. Submucosal tunneling may be particularly suitable for treating small (< 2 cm) ZD because the small pocket may disappear after the myotomy is performed. For larger ZDs (> 2 cm), however, division of some of the mucosa is also required to create a common channel between the diverticulum and the native esophageal lumen, which ensures proper drainage of the ZD. Data comparing the efficacy of POEM with other approaches are lacking, and expertise in Z-POEM is not widely available”. Moreover, Z-POEM is not mentioned in the “Summary and Recommendations” section of this review.

Furthermore, an UpToDate review on “Peroral endoscopic myotomy (POEM)” (Khashab, 2021) states that “POEM for Zenker's diverticula -- A variety of endoscopic techniques have been described for the treatment of Zenker's diverticula (ZD) with clinical success rates between 56 and 100 % and adverse events in an average of 15 % of cases. Clinical recurrence occurs in 10.5 % of patients, but recurrence rates up to 35 % have been reported. It is not possible to accurately delineate the terminal end of the diverticulum during standard endoscopic Zenker's septotomy, and recurrence has been linked to incomplete septotomy. POEM could be a promising technique to allow complete transection of ZD septum (Z-POEM) as submucosal tunneling enables complete exposure and dissection of the septum. This may result in diminishing the risk of symptom recurrence”.

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 tunnelling, 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 tunnelling 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.

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.

Furthermore, an UpToDate review on “Electrical stimulation for gastroparesis” (Hasler, 2023) states that “Temporary stimulator -- Use of endoscopically placed temporary stimulating electrodes have been employed by some centers of expertise to help predict who might respond to a permanently implanted device. Percutaneous electrodes have been proposed as a means of delivering high-energy pacing stimuli from external current sources”. However, the use of temporary stimulator to help predict who might respond to a permanently implanted device is not mentioned in the “Summary and Recommendations” section of this UTD review.

References

The above policy is based on the following references:

Gastric Pacing and Gastric Electrical Stimulation for Gastroparesis

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Gastric Pacing and Gastric Electrical Stimulation for Obesity and Diabetes

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Cha R, Marescaux J, Diana M. Updates on gastric electrical stimulation to treat obesity: Systematic review and future perspectives. World J Gastrointest Endosc. 2014;6(9):419.
Cigaina V, Hirschberg AL. Gastric pacing for morbid obesity: Plasma levels of gastrointestinal peptides and leptin. Obes Res. 2003;11(12):1456-1462.
Cigaina V, Hirschberg AL. Plasma ghrelin and gastric pacing in morbidly obese patients. Metabolism. 2007;56(8):1017-1021.
Cigaina V. Long-term follow-up of gastric stimulation for obesity: The Mestre 8-year experience. Obes Surg. 2004;14 Suppl 1:S14-S22.
Cigaina V. Gastric pacing as therapy for morbid obesity: Preliminary results. Obes Surg. 2002;12 Suppl 1:12S-16S.
Deitel M, Shikora SA. Introduction. Gastric pacing for obesity. Obes Surg. 2002;12 Suppl 1:2S.
Greenstein RJ, Belachew M. Implantable gastric stimulation (IGS) as therapy for human morbid obesity: Report from the 2001 IFSO symposium in Crete. Obes Surg. 2002;12 Suppl 1:3S-5S.
Hasler WL. Methods of gastric electrical stimulation and pacing: A review of their benefits and mechanisms of action in gastroparesis and obesity. Neurogastroenterol Motil. 2009;21(3):229-243.
Jensen MD. Potential role of new therapies in modifying cardiovascular risk in overweight patients with metabolic risk factors. Obesity (Silver Spring). 2006;14 Suppl 3:143S-149S.
Liu S, Hou X, Chen JD. Et al. Therapeutic potential of duodenal electrical stimulation for obesity: Acute effects on gastric emptying and water intake. Am J Gastroenterol. 2005;100(4):792-796.
Ma J, Rayner CK, Jones KL, Horowitz M. Diabetic gastroparesis: Diagnosis and management. Drugs. 2009;69(8):971-986.
Maisiyiti A, Chen JD. Systematic review on gastric electrical stimulation in obesity treatment. Expert Rev Med Devices. 2019;16(10):855-861.
McCallum RW, Snape W, Brody F, et al. Gastric electrical stimulation with Enterra therapy improves symptoms from diabetic gastroparesis in a prospective study. Clin Gastroenterol Hepatol. 2010;8(11):947-954.
McNatt SS, Longhi JJ, Goldman CD, McFadden DW. Surgery for obesity: A review of the current state of the art and future directions. J Gastrointest Surg. 2007;11(3):377-397.
Mintchev MP. Gastric electrical stimulation for the treatment of obesity: From entrainment to bezoars-a functional review. ISRN Gastroenterol. 2013;2013:434706.
Mizrahi M, Ben Ya'acov A, Ilan Y. Gastric stimulation for weight loss. World J Gastroenterol. 2012;18(19):2309-2319.
Morales-Conde S, Alarcon Del Agua I, Busetto L, et al. Implanted closed-loop gastric electrical stimulation (CLGES) system with sensor-based feedback safely limits weight regain at 24 months. Obes Surg. 2018;28(6):1766-1774.
Ouyang H, Yin J, Chen JD. Therapeutic potential of gastric electrical stimulation for obesity and its possible mechanisms: A preliminary canine study. Dig Dis Sci. 2003;48(4):698-705.
Paulus GF, van Avesaat M, van Rijn S, et al. Multicenter, phase 1, open prospective trial of gastric electrical stimulation for the treatment of obesity: First-in-human results with a novel implantable system. Obes Surg. 2020;30(5):1952-1960.
Policker S, Haddad W, Yaniv I. Treatment of type 2 diabetes using meal-triggered gastric electrical stimulation. Isr Med Assoc J. 2009;11(4):206-208.
Salvi PF, Brescia A, Cosenza UM, et al. Gastric pacing to treat morbid obesity: Two years experience in four patients. Ann Ital Chir. 2009;80(1):25-28.
Sanmiguel CP, Conklin JL, Cunneen SA, et al. Gastric electrical stimulation with the TANTALUS System in obese type 2 diabetes patients: Effect on weight and glycemic control. J Diabetes Sci Technol. 2009;3(4):964-970.
Sanmiguel CP, Haddad W, Aviv R, et al. The TANTALUS system for obesity: Effect on gastric emptying of solids and ghrelin plasma levels. Obes Surg. 2007;17(11):1503-1509.
Shikora SA, Bergenstal R, Bessler M, et al. Implantable gastric stimulation for the treatment of clinically severe obesity: Results of the SHAPE trial. Surg Obes Relat Dis. 2009;5(1):31-37.
Swedish Council on Technology Assessment in Healthcare (SBU). Gastric pacing (gastric electrical stimulation) for the treatment of obesity -- early assessment briefs (Alert). Stockholm, Sweden: SBU; 2004.
Thazhath SS, Jones KL, Horowitz M, Rayner CK. Diabetic gastroparesis: Recent insights into pathophysiology and implications for management. Expert Rev Gastroenterol Hepatol. 2013;7(2):127-139.
Yao S, Ke M, Wang Z, et al. Retrograde gastric pacing reduces food intake and delays gastric emptying in humans: A potential therapy for obesity? Dig Dis Sci. 2005;50(9):1569-1575.

Gastric Pacing and Gastric Electrical Stimulation for Gastro-Intestinal Dysmotility

Sallam HS, McNearney TA, Chen JD. Acupuncture-based modalities: Novel alternative approaches in the treatment of gastrointestinal dysmotility in patients with systemic sclerosis. Explore (NY). 2014;10(1):44-52.

Gastric Pacing and Gastric Electrical Stimulation for Cyclic Vomiting Syndrome and Selected Indications

Grover I, Kim R, Spree DC, et al. Gastric electrical stimulation is an option for patients with refractory cyclic vomiting syndrome. J Neurogastroenterol Motil. 2016;22(4):643-649.
Lee S, Abd-Elsayed A. Some non-FDA approved uses for neuromodulation in treating autonomic nervous system disorders: A discussion of the preliminary support. Neuromodulation. 2016;19(8):791-803.

Gastric Per-Oral Endoscopic Myotomy

Abdelfatah MM, Li B, Kapil N, et al. Short-term outcomes of double versus single pyloromyotomy at peroral endoscopic pyloromyotomy in the treatment of gastroparesis (with video). Gastrointest Endosc. 2020;92(3):603-609.
Aghaie Meybodi M, Qumseya BJ, Shakoor D, et al. Efficacy and feasibility of G-POEM in management of patients with refractory gastroparesis: A systematic review and meta-analysis. Endosc Int Open. 2019;7(3):E322-E329.
Camilleri M. Treatment of gastroparesis. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed April 2019; May 2021.
Camilleri M, Kuo B, Nguyen L, et al. ACG Clinical Guideline: Gastroparesis. Am J Gastroenterol. 2022;117(8):1197-1220.
Dacha S, Wang L, Li X, et al. Outcomes and quality of life assessment after per oral endoscopic myotomy (POEM) performed in the endoscopy unit with trainees. Surg Endosc. 2018;32(7):3046-3054.
Gonzalez JM, Benezech A, Vitton V, et al. G-POEM with antro-pyloromyotomy for the treatment of refractory gastroparesis: Mid-term follow-up and factors predicting outcome. Aliment Pharmacol Ther. 2017;46(3):364-370.
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.
Kahaleh M, Gonzalez JM, Xu MM, et al. Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: A multicenter international experience. Endoscopy. 2018;50(11):1053-1058.
Khashab MA. Peroral endoscopic myotomy (POEM). UpToDate [online serial], Waltham, MA: UpToDate; reviewed April 2019.
Khashab MA, Ngamruengphong S, Carr-Locke D, et al. Gastric per-oral endoscopic myotomy for refractory gastroparesis: Results from the first multicenter study on endoscopic pyloromyotomy (with video). Gastrointest Endosc. 2017;85(1):123-128.
Khoury T, Mizrahi M, Mahamid M, et al. State of the art review with literature summary on gastric peroral endoscopic pyloromyotomy for gastroparesis. J Gastroenterol Hepatol. 2018;33(11):1829-1833.
Kozlov Y, Kovalkov K, Smirnov A. Gastric peroral endoscopic myotomy for treatment of congenital pyloric stenosis -- First clinical experience. J Laparoendosc Adv Surg Tech A. 2019;29(6):860-864.
Kristensen HO, Bjerregaard NC, Rask P, et al. Peroral endoscopic myotomy (POEM) for nutcracker esophagus. Three cases with 12 months follow-up. Scand J Gastroenterol. 2014;49(11):1285-1289.
Lacy BE, Tack J, Gyawali CP. AGA Clinical practice update on management of medically refractory gastroparesis: Expert review. Clin Gastroenterol Hepatol. 2022;20(3):491-500.
Lebares C, Swanstrom LL. Per-oral pyloromyotomy (POP): An emerging application of submucosal tunneling for the treatment of refractory gastroparesis. Gastrointest Endosc Clin N Am. 2016;26(2):257-270.
Li P, Ma B, Gong S, et al. Gastric per-oral endoscopic myotomy for refractory gastroparesis: A meta-analysis. J Gastrointest Surg. 2021;25(5):1108-1116.
Malik Z, Kataria R, Modayil R, et al. Gastric per oral endoscopic myotomy (G-POEM) for the treatment of refractory gastroparesis: Early experience. Dig Dis Sci. 2018;63(9):2405-2412.
Martinek J, Hustak R, Mares J, et al. Endoscopic pyloromyotomy for the treatment of severe and refractory gastroparesis: A pilot, randomised, sham-controlled trial. Gut. 2022;71(11):2170-2178.
Mekaroonkamol P, Li LY, Dacha S, et al. Gastric peroral endoscopic pyloromyotomy (G-POEM) as a salvage therapy for refractory gastroparesis: A case series of different subtypes. Neurogastroenterol Motil. 2016;28(8):1272-1277.
Mekaroonkamol P, Patel V, Shah R, et al. Association between duration or etiology of gastroparesis and clinical response after gastric per-oral endoscopic pyloromyotomy. Gastrointest Endosc. 2019;89(5):969-976.
Mohan BP, Chandan S, Jha LK, et al. Clinical efficacy of gastric per-oral endoscopic myotomy (G-POEM) in the treatment of refractory gastroparesis and predictors of outcomes: A systematic review and meta-analysis using surgical pyloroplasty as a comparator group. Surg Endosc. 2020;34(8):3352-3367.
Myint AS, Rieders B, Tashkandi M, et al. Current and emerging therapeutic options for gastroparesis. Gastroenterol Hepatol (N Y). 2018;14(11):639-645.
Nabi Z, Talukdar R, Chavan R, et al. Outcomes of per-oral endoscopic myotomy in children: A systematic review and meta-analysis. Dysphagia. 2022;37(6):1468-1481.
Ragi O, Jacques J, Branche J, et al. One-year results of gastric peroral endoscopic myotomy for refractory gastroparesis: A French multicenter study. Endoscopy. 2021;53(5):480-490.
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.
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.
Khashab MA. Peroral endoscopic myotomy (POEM). UpToDate [online serial]. Waltham, MA: UpToDate; reviewed May 2021.
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.
Schiff B, van Delft F. Zenker's diverticulum. UpToDate [online serial]. Waltham, MA: UpToDate; reviewed May 2021.
Stasek M, Neoral C, Zhydkov R, et al. Current possibilities of minimally invasive therapy of oesophageal diverticula. Rozhl Chir. 2020;99(4):152-158.
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.

Last Review 09/25/2023

Effective: 02/06/2004

Next Review: 07/25/2024
Review History
Definitions

Gastric Pacing / Electrical Stimulation and Gastroesophageal Per Oral Endoscopic Myotomy

Table Of Contents

Policy

Scope of Policy

Medical Necessity

Experimental and Investigational

Related Policies

CPT Codes / HCPCS Codes / ICD-10 Codes

CPT codes covered if selection criteria are met:

CPT codes not covered for indications listed in the CPB:

Diverticular peroral endoscopic myotomy (D-POEM), temporary gastric electrical stimulation (GES) - no specific code:

Other CPT codes related to the CPB:

HCPCS codes covered if selection criteria are met:

ICD-10 codes covered if selection criteria are met:

ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):

Background

Gastric Pacing and Gastric Electrical Stimulation for Gastro-Intestinal Dysmotility

Gastric Pacing and Gastric Electrical Stimulation for Cyclic Vomiting Syndrome

Gastric Pacing and Gastric Electrical Stimulation for Autonomic Nervous System Disorders

Gastric Pacing and Gastric Electrical Stimulation for the Treatment of Obesity

Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Gastroparesis

Gastric Peroral Endoscopic Myotomy for the Treatment of Congenital Hypertrophic Pyloric Stenosis

Diverticular Peroral Endoscopic Myotomy (D-POEM) for the Treatment of Esophageal Diverticulum

Zenker POEM (Z-POEM) Diverticulotomy for Closing Defect due to Zenker's Diverticulum

Temporary Gastric Electrical Stimulation (GES) for the Prediction of Success of GES in the Treatment of Gastroparesis

References

Gastric Pacing and Gastric Electrical Stimulation for Gastroparesis

Gastric Pacing and Gastric Electrical Stimulation for Obesity and Diabetes

Gastric Pacing and Gastric Electrical Stimulation for Gastro-Intestinal Dysmotility

Gastric Pacing and Gastric Electrical Stimulation for Cyclic Vomiting Syndrome and Selected Indications

Gastric Per-Oral Endoscopic Myotomy

Diverticular Peroral Endoscopic Myotomy (D-POEM) / Zenker POEM (Z-POEM) Diverticulotomy

Policy History

Additional Information

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