Per Oral Pyloromyotomy (POP): Future Directions

Most studies on the POP procedure have been retrospective in nature; therefore, further prospective randomized controlled studies are still needed. Challenges in investigating the POP procedure include the following: (1) unlike POEM, there is no gold standard intervention for gastroparesis for POP to be compared with; (2) outcome measurements are mainly patient reported and subject to recall bias and placebo effect; (3) gastric emptying study as an objective measure of improvement of gastroparesis does not correlate well with gastroparesis symptoms; and (4) the low prevalence of gastroparesis makes it difficult to study [73]. Despite the challenges, studies looking at the long-term results of the POP compared to other endoscopic treatment modalities and laparoscopic pyloromyotomy are necessary. Two randomized prospective studies are ongoing in France comparing POP to botulinum toxin injection for refractory gastroparesis (NCT02927886) and an international study comparing POP to placebo with long-term follow-up (NCT03356067) [84]. However, these studies do not evaluate the individual pyloric function, and therefore the suitability of the patients studied may be called into question. Rather, studies should aim to predict which patients are more likely to respond to a POP procedure. Gastroparesis subtyping and patient selection may also help to maximize and better guide further management of refractory gastroparesis. Gonzalez et al. suggested diabetes and female gender were associated with poorer response, but this was not demonstrated in other studies. Better clinical outcomes were noted when POP is performed in patients with idiopathic or postoperative gastroparesis compared to diabetic gastroparesis [67, 73]. Pyloric-directed therapies have been shown to improve gastric emptying time, nausea/vomiting, and early satiety, with less effects on bloating and pain. Nausea and vomiting were consistently found to be the most responsive symptoms after POP [39, 48, 72, 77]. This is believed to be due to nausea and vomiting resulting from impaired pyloric distensibility and therefore amenable to improvement with POP [70, 72, 73, 87]. Early satiety, bloating, and abdominal pain are thought to be due to impaired postprandial fundal relaxation and visceral hypersensitivity making these symptoms less amenable to improvement with POP or pyloric-directed therapy [73, 88–90]. Therefore, subtyping based on the cause of gastroparesis or symptoms may also predict patient outcomes after treatment. An emphasis on preoperative workup may help identify patients with pylorospasm who would have a high likelihood of responding to pyloromyotomy. Antroduodenal manometry, impedance planimetry, and wireless motility capsule may be tools to evaluate pyloric function. By quantifying preprocedure manometric measurements and correlating it to improvement post POP procedure, a patient’s response after pyloromyotomy may be predicted based on preoperative workup. Endoflip technology may assist with identifying pylorospasm by selecting patients with a pylorus with smaller diameter and cross-sectional area that may demonstrate the greatest technical and clinical improvement with a POP procedure which would aims to decrease pyloric pressure and improve pyloric distensibility. Another study demonstrated that the lower initial Gastroparesis Cardinal Symptom Index (GCSI) score resulted in a better response to the treatment suggesting that perhaps pyloromyotomy should be performed earlier in the disease course rather than in patients refractory to other treatments [33]. The POP procedure is also beneficial in that it does not preclude the option to pursue further surgical interventions if symptoms persist. Additionally, due to the incisionless element of the POP, it may be preferable in patients with a history of abdominal surgeries that may complicate intra-abdominal treatment approaches to gastroparesis. As the POP procedure further advances, it may be investigated as a treatment option earlier in the course of gastroparesis treatment.

Currently, the POP procedure is still a technically demanding procedure performed by highly skilled endoscopists in highly specialized centers at a few tertiary centers. By further studying and identifying the benefits of the POP procedure such as reducing gastroparesis symptoms, improving quality of life, decreasing gastric emptying time, and decreasing use of health care resources for patients with refractory gastroparesis, the benefit of the POP procedure may be further elucidated [77]. By recognizing its great potential and demonstrating reproducible safe and effective results, a refined and standardized technique may be developed. This may lead to more widespread training of endoscopists and greater availability of the POP procedure for gastroparesis patients beyond tertiary centers. Management of gastroparesis extends beyond performing technical procedures but requires the development of a multidisciplinary approach involving a gastroenterology motility specialist, dietitian, psychologist, pain management specialist, and a general surgeon. This multidisciplinary approach facilitates proper evaluation, nutritional optimization, chronic pain rehabilitation, and patient education regarding the diagnosis and management of gastroparesis to optimize patient outcomes [70].

Endoscopic Gastric Electrical Stimulation

The Enterra therapy system (Medtronic Inc., Dublin, Ireland) gastric electrical stimulator (GES) consists of a small implantable electrical generator and two electrodes placed in the gastric wall [2, 91]. Although the physiologic mechanism is not clearly understood, about 50–90% of patients have some improvement in the context of a 7–14% rate of morbidity with the procedure itself [2, 91–95]. The data supporting GES devices has not been completely convincing. Due to the paucity of treatment options for gastroparesis, in the USA 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. There is little evidence that it improves gastric emptying, but supportive evidence relates mostly to relief from nausea and vomiting. These are generally placed laparoscopically; however, endeavors to develop temporary and more permanent GES devices that may be placed endoscopically are being developed [5]. Temporary GES may allow for a minimally invasive means of identifying patients likely to benefit from permanent GES implantation. In 2005, Ayinala et al. were able to demonstrate the safety and feasibility of an endoscopically placed temporary GES in 20 patients [5, 96]. This involved placing temporary leads endoscopically with an endoclip with the correspondent wire exteriorized through the nose (EndoStim) or through a PEG tube (PEGStim) and connected to the Enterra system generator [2, 93]. The temporary electrodes can be left in place from 3 to 14 days. Although no long-term data exists, the gastric stimulation led to rapid improvement in symptoms and improved vomiting after 72 hours of treatment [5, 97]. Patients with symptomatic improvement with the temporary GES should be followed with a permanent device. Additionally, a completely endoscopically implantable miniature GES was developed. It is wirelessly powered and can stand charge for up to 3 months of use. As of yet, it has been tested in a porcine model but needs to be further evaluated for safety and efficacy in humans [5, 97–100].

Endoscopic Palliative Bypass

Endoscopic ultrasound (EUS)- guided gastroenterostomy (GE) may provide a palliative bypass in refractory gastroparesis. Palliative surgical bypass GE without gastrectomy has been well-described for treating unresectable malignant gastric outlet obstruction (GOO) [5, 101, 102]. Lumen-apposing metal stents (LAMS) are FDA-approved for drainage of pancreatic pseudocysts but have also been evaluated for other investigational uses including EUS-guided GE. Although it has not been studied in refractory gastroparesis, a multicenter study has shown the feasibility of LAMS in both malignant and benign GOO (92% technical success, 85% clinical success, 11.5% adverse event rate) [5, 103]. Additionally, endoscopic GE has been found to be a non-inferior and less invasive alternative to surgical GE [5, 104]. In brief, an EUS-guided GE is performed by using a 22-gauge needle to perform a transgastric puncture into the opposing jejunal lumen. A 19-gauge needle is used to coil a wire in the distended jejunum. A gastroenterostomy tract is dilated and a stent may be placed across the tract [1]. Other techniques involve the use of a biliary stone retrieval balloon, dilation balloon, or double-balloon enteric tube which can bypass the area of obstruction or the pylorus and create a contrast-filled area to be used as a target for transgastric EUS-guided FNA needle puncture [1, 105]. As a result, a communication is created between the stomach and jejunum resulting in a gastroenterostomy to bypass the pylorus.

Endoscopic Pyloroplasty with Full-Thickness Transgastric and Transduodenal Myotomy with Sutured Closure

Endoscopic pyloroplasty with full-thickness transgastric and transduodenal myotomy with suture closure was described by Park et al. in a porcine model [51]. An Olympus double-channel gastroscope (2T 160 [Olympus Optical Co, Ltd., Tokyo, Japan] and 2T 100 [Olympus America Inc., Center Valley, Pa]) were used. A prototype endoscopic tissue approximation kit (InScope; Ethicon Endo-Surgery), 11–15, was used for sutured closure. Suturing was performed by using a metal tag attached to a 3.0 polypropylene thread passed through the endoscope accessory channel inside a 19-gauge hollow needle. Two threads were tied together by using prototype locks. Before making the pyloroplasty, a stitch was placed at the apex of the planned cut in the duodenum and at the start point on the gastric side of the pylorus. A full-thickness incision was then made on the opposite side of the pylorus. The full-thickness nature of the cut was confirmed with an intra-abdominal Veress needle. Stitches placed on the apex of the duodenal incision and the proximal margin on the gastric portion of the incision were locked together. Stitches were then placed on either side of the incision to close the incision transversely. Three or four pairs of stitches were used to complete the pyloroplasty. Six of the seven pigs recovered well without complications. Although not frequently implemented, the use of pyloroplasty with myotomy with sutured closure by flexible endoscopy may be further investigated as an endoscopic treatment option of gastroparesis [51].

Conclusion

Gastroparesis is a functional disorder that has been notoriously difficult to treat. Surgical efforts have ranged from a pyloroplasty to placing a foreign body such as a gastric electrical stimulator with variable outcomes to an invasive subtotal or total gastrectomy. As such, efforts are becoming progressively more focused on minimally invasive and endoscopic techniques that are comparable to more invasive surgical procedures. Endoscopic treatment ranges from nutritional support to pyloric-directed therapies including the application of botulinum toxin, dilation, and stenting. More recently, however, the G-POEM or POP has demonstrated promising results and is becoming the first-line treatment for gastroparesis in available settings. As further long-term data and studies are completed, the use of technology such as Endoflip may help to guide the management decisions for gastroparesis.