A brief history and future directions of permanent, temporary, and endoscopic GES

Introduction

Gastroparesis (Gp) is a syndrome characterized by delayed gastric emptying in the absence of mechanical obstruction and it is associated with symptoms of early satiety, nausea, vomiting, abdominal pain, and bloating. However, these identical symptoms can occur in patients without delayed, or even with rapid gastric emptying. For that reason, some have advocated using the term gastroparetic syndromes. While most Gp is idiopathic, diabetes, post-surgical, neurological diseases, and drugs are associated with many other cases . Medical therapy is first-line in treating Gp; however, over 30% of patients fail initial management. Patients who fail conservative therapy often end up requiring multiple hospitalizations and having a poor quality of life. When patients’ symptoms fail to improve with medical therapy, the next steps may vary. If there is evidence of obstructive Gp, pyloric therapy may be considered. Another option to consider is a gastric electric stimulator (GES) for medically-refractory Gp symptoms. GES can be temporary or permanent, and both methods have been shown over the years to greatly improve symptoms . ( Fig. 38.1 ) This chapter aims to discuss the history of gastric electrical stimulation, temporary and permanent GES including endoscopic neuromodulation therapies, and future methods, direction, and therapies, for GES particularly in medically refractory gastroparesis.

Background and history of GES

The enteric nervous system (ENS) has a very complex organizational structure and can function as a separate unit with modulation by a number of factors. The gastrointestinal (GI) tract is composed of two muscular layers with an embedded neural circulatory system, which controls the coordinated peristalsis throughout the GI tract. Those peristaltic signals are carried through the interstitial cells of Cajal (ICC) and other neuro-muscular structures, and are influenced by neuro-hormonal factors . ( Fig. 38.2 ).

To understand the mechanism of gastric electrical stimulation (GES), one must first understand gastric myoelectric activity. Gastric myoelectric activity consists of uninterrupted electrical potentials called slow waves that initiate proximally near the greater curvature and propagate distally along the gastric wall until the pylorus . The mechanism of the gastric slow wave electrical potentials can be thought of similarly to the conduction system of the heart, with some important differences. GI slow waves actively spread into more distal neighboring cells and force each subsequent cell to oscillate at the same frequency, propagating the gastric smooth muscles to contract . These electrical potentials/slow waves originate from the ICC type 1, under the influence of the Auerbach plexus, mediated by the cholinergic excitatory and adrenergic inhibitory inputs. Disorders of ICC numbers, structure and function are associated with the disordered coordination of slow waves, which contributes greatly to the pathogenesis of gastroparesis, specifically in diabetic gastroparesis as ICC are depleted in patients with diabetic gastroparesis .

The use of electric stimulation to treat pathologies of the GI system dates back to 1911 when William H. Dieffenbach successfully treated chronic constipation and post-operative ileus by rectally placing electrodes and inducing neurostimulation . It wasn’t until 1963 when GES was truly introduced. Bilgutay and colleagues attempted to treat an ileus by nasogastric placing of electrodes onto the gastric wall and inducing stimulation at a set interval. This was done to induce motility and relieve patients of their ileus . A 1992 canine study showed the ability of electrical stimulation to successfully pace the gastrointestinal system. During that study, electrodes were implanted along the gastric wall . Since then, gastric electric stimulation has been developed for use on patients with GI symptoms and gastroparesis. Permanent gastric electrical stimulator devices require surgery, and due to uncertainty of patient response, temporary electrical stimulation was introduced. In the early 1990s, electrodes were introduced via a PEG. In 2001, temporary GES started to be done endoscopically. Active fixation pacing leads, screwed into the mucosa, were initially used, but now passive fixation leads, placed alongside the mucosa, are used and are held in place with endoscopic clips .

There are at least two types of current GI stimulations that have been hypothesized as ways to treat gastroparesis. One is a low-frequency, high-energy stimulation and the other is a high-frequency, low-to-medium energy stimulation . High-frequency GES therapy is what is currently available, and it provides a spectrum of clinical benefits that improve symptoms, nutritional status, and when used in medium energy, changes in gastric emptying . The double-blinded control study, Worldwide Antivomiting Electrical Stimulation Study (WAVESS), published in 2003, showed significant improvement in vomiting and abdominal pain post GES implantation Additional studies have shown that GES therapy improves exocrine pancreatic function, improving digestion As alluded to above, many patients with low-energy devices find that increasing energy levels gives them better symptom control, so this technology can also deliver medium, or intermediate energy ( Fig. 38.3 ).

Current GES therapies

The current type of GES that is commercially available to treat gastroparesis is high frequency, low- energy stimulation, although as mentioned above, many patients use medium energy settings over time. This stimulus applies pulses with duration in microseconds at a hertz frequency. Studies through the years have shown that optimal pacing of the stomach could be achieved with stimulation at a frequency that is slightly higher than the intrinsic gastric slow wave frequency in the stomach in humans with a duration pulse in milliseconds. Other studies have also shown that using even shorter duration pulses, at microseconds, and at higher frequencies could improve symptoms such as nausea and vomiting . Based on these clinical studies, the Food and Drug Administration (FDA) approved the implantable device (trade name Enterra) for gastric electrical stimulation to treat gastroparesis and its associated symptoms that are refractory to medical treatment. Enterra, produced by Medtronic, is the only device that’s commercially currently available that is approved by the FDA to treat patients with idiopathic or diabetic gastroparesis who have failed maximal medical therapy . Some work has shown that diabetic gastroparesis patients responded to GES better than those with idiopathic gastroparesis, and women more so than men, and also showed that patients with a recent diagnosis responded better than patients with long-standing gastroparesis .

The currently available GES system is implanted surgically via laporatomy or, more commonly now, laproscopically, which is a less invasive approach. The whole system consists of a pair of leads, a pulse generator, and a programming system. The leads are surgically placed on the gastric wall in the muscularis propria of the greater curvature, about 10 cm proximal to the pylorus. The leads are then connected to the pulse generator, which is placed in a subcutaneous pocket, typically in the abdominal wall. An external programming device is used to control the pulse generator. Battery life is typically five or more years, depending on device energy settings. Whenever it is time for the battery to be changed, this can be done without having to remove the electrodes. The pulse generator is removed from the subcutaneous pocket in the abdominal wall, the battery is changed, and then it is returned to the pocket .