Study Looks at Combo Treatment for Refractory Gastroparesis

It has been 25 years since the first and only gastric electrical stimulation (GES) device was approved by the U.S. Food and Drug Administration (FDA) through the humanitarian device exemption process for the treatment of gastroparesis. Since then more than 15,000 patients nationwide have undergone GES for symptom relief.

“Gastroparesis has no cure and symptom management remains a challenge with limited therapeutic options,” says Raul Rosenthal, MD, Director of the Bariatric & Metabolic Institute at Cleveland Clinic Weston Hospital. “Gastric electrical stimulation is one of the few treatments we can offer patients with medically refractory disease.”

Studies indicate that some patients benefit from reduced symptoms and quality-of-life improvements following GES therapy with the Enterra® system, though the mechanisms at work are not fully understood. Researchers are still trying to determine who would benefit most from its use, while others are exploring opportunities to improve its effectiveness by pairing GES with other surgical interventions.

Dr. Rosenthal and a team from Cleveland Clinic in Florida recently added to the body of research with a single-center retrospective analysis, published in the journal Surgical Endoscopy, that evaluated the potential benefit of a concomitant pyloromyotomy during GES.

Treating gastroparesis

Gastroparesis is a rare gastric motility disorder that is defined by delayed gastric emptying in the absence of mechanical obstruction. Cardinal symptoms include nausea, vomiting, epigastric pain, and early satiety. The main causes of gastroparesis are diabetes mellitus and idiopathic disease. Other risk factors include gastrointestinal surgery, medications, and neurological and autoimmune disorders.

The first-line treatment for patients with proven gastroparesis typically involves dietary modification, prokinetic and antiemetic medications, and nutritional support, if necessary. Optimal glucose control is also a treatment focus for patients with diabetic gastroparesis.

“Most of our patients with gastroparesis respond well to medical management, but about 20% to 30% will require additional treatments,” reports Dr. Rosenthal.

Patients with refractory gastroparesis may be evaluated for GES device implantation or therapeutic pyloric interventions, such as laparoscopic pyloromyotomy or gastric peroral endoscopic myotomy (G-POEM). In severe cases, a gastrectomy may be performed as a treatment of last resort.

Gastric electrical stimulation

As an early adopter, Cleveland Clinic Weston Hospital has more than two decades of experience providing GES therapy for patients with refractory gastroparesis. It works by delivering high-frequency, low-energy electrical pulses to the nerves and smooth muscles of the stomach to control gastroparesis-related symptoms, especially nausea and vomiting.

During device implantation, Dr. Rosenthal uses a laparoscopic approach to surgically place the small gastric pacemaker in a subcutaneous pocket in the patient’s left lower abdomen. Two electrodes are inserted into the seromuscular layer of the greater curvature of the stomach and externalized and connected to the neurostimulator’s battery. An external programmer is then used to set stimulation parameters.

“Studies have demonstrated varying success rates with GES, ranging from 45 to 90%,” states Dr. Rosenthal. “In our experience, about 80% of patients achieve symptom relief, especially in lessening their nausea.”

He also points out that while some studies have suggested a placebo effect may be involved, he is confident the treatment is acting on the underlying physiopathology. “I’ve had several patients return to the clinic years later when their symptoms return only to learn that the device’s battery has died,” he says.

In addition, Dr. Rosenthal notes some patients treated at Weston Hospital have experienced delayed improvement in motility several months following device implantation, though GES has not been conclusively established to improve gastric emptying.

A combination approach

“The management of gastroparesis aims to improve both symptoms and gastric emptying, which is why pyloric interventions are also used to treat some patients with refractory gastroparesis,” says Dr. Rosenthal.

A pyloromyotomy, for example, entails cutting through the longitudinal and circular muscle layers of the pylorus to relax and widen the sphincter. This facilitates gastric emptying by allowing food to pass more easily from the stomach into the small intestine. “When pyloromyotomy is offered concomitantly with GES, I’ll perform it prior to device implantation,” he adds.

The goal of the recent retrospective study from Cleveland Clinic in Florida was to evaluate the clinical response duration and perioperative outcomes of GES implantation with pyloromyotomy as a possible surgical alternative to GES implantation alone.

Study findings

The researchers looked at all patients with refractory gastroparesis treated with GES with and without concomitant pyloromyotomy at Cleveland Clinic Weston Hospital from January 2003 to January 2023. A total of 134 patients were identified, most with idiopathic (n = 68, 51.9%) or diabetic (n = 58, 43.3%) gastroparesis.

Three patients were excluded from the analysis due to a prior history of surgical pyloromyotomy or Roux-en-Y gastric bypass. Dr. Rosenthal performed all the surgeries included in the analysis. Forty patients (30.5%) underwent GES with pyloromyotomy and 91 (69.5%) had GES alone.

According to their findings, a higher clinical response rate was observed at 5 years after GES with pyloromyotomy (82%) versus without (62%), but without statistical significance (p = 0.066). They also found that patients with diabetic gastroparesis seemed to benefit more from the combination treatment (5-year success rate 100% versus 67%, p = 0.053) than patients with idiopathic gastroparesis (5-year success rate 75% vs 54%, p = 0.167).

“Our results align with prior reports in the literature of improved clinical outcomes when GES is combined with pyloromyotomy,” says Dr. Rosenthal. “We also observed similar postoperative morbidity and length of hospital stay in the combination treatment when compared to GES alone.”

Latest guidance

The current clinical guidelineissued by the American College of Gastroenterology in 2022 states that GES may be considered for compassionate treatment in individuals with refractory gastroparesis symptoms, particularly nausea and vomiting.

In 2023 the American Society of Metabolic and Bariatric Surgery also issued a guideline statement, which was co-authored by Dr. Rosenthal. It states that the main indication for GES is the presence of gastroparesis (diabetic or idiopathic) with concomitant severe nausea and vomiting who are refractory to medical management for at least 1 year.

“While there is no consensus on which treatment approaches are most appropriate and effective for refractory gastroparesis, our study provides further evidence that a combination of interventions can be safe and beneficial for select patients,” says Dr. Rosenthal.